Ventricular conduction stability noninvasively identifies an arrhythmic substrate in survivors of idiopathic ventricular fibrillation

Background Idiopathic ventricular fibrillation (VF) is a diagnosis of exclusion following normal cardiac investigations. We sought to determine if exercise-induced changes in electrical substrate could distinguish patient groups with various ventricular arrhythmic pathophysiological conditions and identify patients susceptible to VF. Methods and Results Computed tomography and exercise testing in patients wearing a 252-electrode vest were combined to determine ventricular conduction stability between rest and peak exercise, as previously described. Using ventricular conduction stability, conduction heterogeneity in idiopathic VF survivors (n=14) was compared with those surviving VF during acute ischemia with preserved ventricular function following full revascularization (n=10), patients with benign ventricular ectopy (n=11), and patients with normal hearts, no arrhythmic history, and negative Ajmaline challenge during Brugada family screening (Brugada syndrome relatives; n=11). Activation patterns in normal subjects (Brugada syndrome relatives) are preserved following exercise, with mean ventricular conduction stability of 99.2±0.9%. Increased heterogeneity of activation occurred in the idiopathic VF survivors (ventricular conduction stability: 96.9±2.3%) compared with the other groups combined (versus 98.8±1.6%; P=0.001). All groups demonstrated periodic variation in activation heterogeneity (frequency, 0.3-1 Hz), but magnitude was greater in idiopathic VF survivors than Brugada syndrome relatives or patients with ventricular ectopy (7.6±4.1%, 2.9±2.9%, and 2.8±1.2%, respectively). The cause of this periodicity is unknown and was not replicable by introducing exercise-induced noise at comparable frequencies. Conclusions In normal subjects, ventricular activation patterns change little with exercise. In contrast, patients with susceptibility to VF experience activation heterogeneity following exercise that requires further investigation as a testable manifestation of underlying myocardial abnormalities otherwise silent during routine testing

Non-invasive detection of exercise-induced cardiac conduction abnormalities in sudden cardiac death survivors in the inherited cardiac conditions.

AIMS : Rate adaptation of the action potential ensures spatial heterogeneities in conduction across the myocardium are minimized at different heart rates providing a protective mechanism against ventricular fibrillation (VF) and sudden cardiac death (SCD), which can be quantified by the ventricular conduction stability (V-CoS) test previously described. We tested the hypothesis that patients with a history of aborted SCD due to an underlying channelopathy or cardiomyopathy have a reduced capacity to maintain uniform activation following exercise. METHODS AND RESULTS : Sixty individuals, with (n = 28) and without (n = 32) previous aborted-SCD event underwent electro-cardiographic imaging recordings following exercise treadmill test. These included 25 Brugada syndrome, 13 hypertrophic cardiomyopathy, 12 idiopathic VF, and 10 healthy controls. Data were inputted into the V-CoS programme to calculate a V-CoS score that indicate the percentage of ventricle that showed no significant change in ventricular activation, with a lower score indicating the development of greater conduction heterogeneity. The SCD group, compared to those without, had a lower median (interquartile range) V-CoS score at peak exertion [92.8% (89.8-96.3%) vs. 97.3% (94.9-99.1%); P < 0.01] and 2 min into recovery [95.2% (91.1-97.2%) vs. 98.9% (96.9-99.5%); P < 0.01]. No significant difference was observable later into recovery at 5 or 10 min. Using the lowest median V-CoS scores obtained during the entire recovery period post-exertion, SCD survivors had a significantly lower score than those without for each of the different underlying aetiologies. CONCLUSION : Data from this pilot study demonstrate the potential use of this technique in risk stratification for the inherited cardiac conditions

Proarrhythmogenic effects of lamotrigine during ajmaline testing for Brugada syndrome.

Sodium channel blockade (SCB) with a class Ia or Ic antiarrhythmic agent (eg, ajmaline or procainamide, respectively) is used in the unmasking and diagnosis of Brugada syndrome (BrS). SCB is performed frequently as part of family screening or in symptomatic patients with a suggestive electrocardiogram (ECG), and concurrent medications known to potentiate arrhythmias or contraindicated in BrS are withheld prior to testing.1 Lamotrigine (LTG) is currently not contraindicated in BrS or known to be potentially arrhythmic during testing with SCB agents. We report a case illustrating its arrhythmogenic potential and the implications of its concurrent usage during such testing in clinical practice

Comparison of the prognostic usefulness of the European Society of Cardiology and American Heart Association/American College of Cardiology Foundation risk stratification systems in patients with Hypertrophic Cardiomyopathy

Implantable cardio-defibrillators (ICDs) have proven benefit in preventing sudden cardiac death (SCD) in hypertrophic cardiomyopathy (HC), making risk stratification essential. Data on the predictive accuracy on the European Society of Cardiology (ESC) risk scoring system has been conflicting. We independently evaluated the ESC risk scoring system in our cohort of HC patients from a large tertiary centre and compared this to previous guidance by the American College of Cardiology Foundation and Heart Association (ACCF/AHA). Risk factor profiles, 5-year SCD risk estimates and ICD recommendations as defined by the ACCF/AHA and ESC guidelines, were retrospectively ascertained for 288 HC patients with and without SCD or equivalent events at our centre. In the SCD group (n=14), a significantly higher proportion of patients would not have met the criteria for an ICD implant using the ESC scoring algorithm than ACCF/AHA guidance (43%vs7%, p=0.029). In those without SCD events (n=274), a larger proportion of individuals not requiring an ICD was identified using the ESC risk score model compared to the ACCF/AHA model (82%vs57%; p<0.0001). Based on risk stratification criteria alone, 5 more individuals with a previously aborted SCD event would not have received an ICD with the ESC risk model than the ACCF/AHA risk model. In conclusion, we found that the current ESC scoring system potentially leaves more high-risk patients unprotected from sudden death in our cohort of patients

ST-Elevation Magnitude Correlates With Right Ventricular Outflow Tract Conduction Delay in Type I Brugada ECG

Background: The substrate location and underlying electrophysiological mechanisms that contribute to the characteristic ECG pattern of Brugada syndrome (BrS) are still debated. Using noninvasive electrocardiographical imaging, we studied whole heart conduction and repolarization patterns during ajmaline challenge in BrS individuals. Methods and Results: A total of 13 participants (mean age, 44±12 years; 8 men), 11 concealed patients with type I BrS and 2 healthy controls, underwent an ajmaline infusion with electrocardiographical imaging and ECG recordings. Electrocardiographical imaging activation recovery intervals and activation timings across the right ventricle (RV) body, outflow tract (RVOT), and left ventricle were calculated and analyzed at baseline and when type I BrS pattern manifested after ajmaline infusion. Peak J-ST point elevation was calculated from the surface ECG and compared with the electrocardiographical imaging–derived parameters at the same time point. After ajmaline infusion, the RVOT had the greatest increase in conduction delay (5.4±2.8 versus 2.0±2.8 versus 1.1±1.6 ms; P=0.007) and activation recovery intervals prolongation (69±32 versus 39±29 versus 21±12 ms; P=0.0005) compared with RV or left ventricle. In controls, there was minimal change in J-ST point elevation, conduction delay, or activation recovery intervals at all sites with ajmaline. In patients with BrS, conduction delay in RVOT, but not RV or left ventricle, correlated to the degree of J-ST point elevation (Pearson R, 0.81; P<0.001). No correlation was found between J-ST point elevation and activation recovery intervals prolongation in the RVOT, RV, or left ventricle. Conclusions: Magnitude of ST (J point) elevation in the type I BrS pattern is attributed to degree of conduction delay in the RVOT and not prolongation in repolarization time

Ventricular conduction stability test: a method to identify and quantify changes in whole heart activation patterns during physiological stress

AIMS: Abnormal rate adaptation of the action potential is proarrhythmic but is difficult to measure with current electro-anatomical mapping techniques. We developed a method to rapidly quantify spatial discordance in whole heart activation in response to rate cycle length changes. We test the hypothesis that patients with underlying channelopathies or history of aborted sudden cardiac death (SCD) have a reduced capacity to maintain uniform activation following exercise. METHODS AND RESULTS: Electrocardiographical imaging (ECGI) reconstructs >1200 electrograms (EGMs) over the ventricles from a single beat, providing epicardial whole heart activation maps. Thirty-one individuals [11 SCD survivors; 10 Brugada syndrome (BrS) without SCD; and 10 controls] with structurally normal hearts underwent ECGI vest recordings following exercise treadmill. For each patient, we calculated the relative change in EGM local activation times (LATs) between a baseline and post-exertion phase using custom written software. A ventricular conduction stability (V-CoS) score calculated to indicate the percentage of ventricle that showed no significant change in relative LAT (<10 ms). A lower score reflected greater conduction heterogeneity. Mean variability (standard deviation) of V-CoS score over 10 consecutive beats was small (0.9 ± 0.5%), with good inter-operator reproducibility of V-CoS scores. Sudden cardiac death survivors, compared to BrS and controls, had the lowest V-CoS scores post-exertion (P = 0.011) but were no different at baseline (P = 0.50). CONCLUSION: We present a method to rapidly quantify changes in global activation which provides a measure of conduction heterogeneity and proof of concept by demonstrating SCD survivors have a reduced capacity to maintain uniform activation following exercise

Prevalence of spontaneous type I ECG pattern, syncope, and other risk markers in sudden cardiac arrest survivors with Brugada syndrome

Introduction A spontaneous type I electrocardiogram (ECG) pattern and/or unheralded syncope are conventionally used as risk markers for primary prevention of sudden cardiac arrest/death (SCA/SCD) in Brugada syndrome (BrS). In this study, we determine the prevalence of conventional and newer markers of risk in those with and without previous aborted SCA events. Methods All patients with BrS were identified at our institute. History of symptoms was obtained from medical tests or from interviews. Other markers of risk were also obtained, such as presence of (1) spontaneous type I pattern, (2) fractionated QRS (fQRS), (3) early repolarization (ER) pattern, (4) late potentials on signal‐averaged ECG (SAECG), and (5) response to programmed electrical stimulation. Results In 133 patients with Bars, 10 (7%) patients (mean age = 39 ± 11 years; nine males) were identified with a previous ventricular fibrillation/ventricular tachycardia episode (n = 8) or requiring cardio‐pulmonary resuscitation (n = 2). None of these patients had a prior history of syncope before their SCA event. Only two (20%) patients reported a history of palpitations or dizziness. None had apneic breathing and three (30%) patients had a family history of SCA. From their ECGs, a spontaneous pattern was only found in one (10%) of these patients. Further, 10% of patients had fQRS, 17% had late potentials on SAECG, 20% had deep S waves in lead I, and 10% had an ER pattern in the peripheral leads. No significant differences were observed in the non‐SCA group. Conclusion The majority of BrS patients with previous aborted SCA events did not have a spontaneous type I and/or prior history of syncope. Conventional and newer markers of risk appear to only have limited ability to predict SCA