Early postnatal high-dose fat-soluble enteral vitamin A supplementation for moderate or severe bronchopulmonary dysplasia or death in extremely low birthweight infants (NeoVitaA): a multicentre, randomised, parallel-group, double-blind, placebo-controlled, investigator-initiated phase 3 trial.

BACKGROUND: Vitamin A plays a key role in lung development, but there is no consensus regarding the optimal vitamin A dose and administration route in extremely low birthweight (ELBW) infants. We aimed to assess whether early postnatal additional high-dose fat-soluble enteral vitamin A supplementation versus placebo would lower the rate of moderate or severe bronchopulmonary dysplasia or death in ELBW infants receiving recommended basic enteral vitamin A supplementation. METHODS: This prospective, multicentre, randomised, parallel-group, double-blind, placebo-controlled, investigator-initiated phase 3 trial conducted at 29 neonatal intensive care units in Austria and Germany assessed early high-dose enteral vitamin A supplementation (5000 international units [IU]/kg per day) or placebo (peanut oil) for 28 days in ELBW infants. Eligible infants had a birthweight of more than 400 g and less than 1000 g; gestational age at birth of 32+0 weeks postmenstrual age or younger; and the need for mechanical ventilation, non-invasive respiratory support, or supplemental oxygen within the first 72 h of postnatal age after admission to the neonatal intensive care unit. Participants were randomly assigned by block randomisation with variable block sizes (two and four). All participants received basic vitamin A supplementation (1000 IU/kg per day). The composite primary endpoint was moderate or severe bronchopulmonary dysplasia or death at 36 weeks postmenstrual age, analysed in the intention-to-treat population. This trial was registered with EudraCT, 2013-001998-24. FINDINGS: Between March 2, 2015, and Feb 27, 2022, 3066 infants were screened for eligibility at the participating centres. 915 infants were included and randomly assigned to the high-dose vitamin A group (n=449) or the control group (n=466). Mean gestational age was 26·5 weeks (SD 2·0) and mean birthweight was 765 g (162). Moderate or severe bronchopulmonary dysplasia or death occurred in 171 (38%) of 449 infants in the high-dose vitamin A group versus 178 (38%) of 466 infants in the control group (adjusted odds ratio 0·99, 95% CI 0·73-1·55). The number of participants with at least one adverse event was similar between groups (256 [57%] of 449 in the high-dose vitamin A group and 281 [60%] of 466 in the control group). Serum retinol concentrations at baseline, at the end of intervention, and at 36 weeks postmenstrual age were similar in the two groups. INTERPRETATION: Early postnatal high-dose fat-soluble enteral vitamin A supplementation in ELBW infants was safe, but did not change the rate of moderate or severe bronchopulmonary dysplasia or death and did not substantially increase serum retinol concentrations. FUNDING: Deutsche Forschungsgemeinschaft and European Clinical Research Infrastructures Network (ECRIN).

Focal atrial tachycardia mimicking catecholaminergic polymorphic ventricular tachycardia: a case report.

Background: In childhood and adolescence, cardiac arrhythmias are often benign in the absence of congenital heart defects. Nevertheless, life-threatening inherited arrhythmogenic syndromes can become clinically manifest in early childhood. As early symptoms may be similar in both conditions, thorough workup is fundamental to avoid delayed diagnosis and misdiagnosis. Case summary: We present the case of a 26-year-old Caucasian female patient who presented with recurrent non-sustained polymorphic wide complex tachycardia. Structural heart disease was excluded by echocardiography as well as cardiac magnetic resonance imaging. Due to wide complex extrasystoles and couplets with alternating QRS axis occurring at low levels of physical exertion, catecholaminergic polymorphic ventricular tachycardia (CPVT) was suspected and further investigated. Epinephrine testing in combination with an electrophysiological (EP) study with placement of a coronary sinus catheter and subsequent programmed stimulation ruled out CPVT and unmasked wide complex tachycardia as varying aberrant conduction of focal atrial tachycardia (FAT). 3D-navigated mapping of FAT revealed a direct parahisian origin. Due to significantly increased risk of atrio-ventricular (AV) block during ablation, the patient refused ablation and preferred medical antiarrhythmic therapy. Discussion: Given the consequences of both, delayed diagnosis and misdiagnosis of CPVT, thorough workup is fundamental. In case of doubt regarding potential aberrant AV conduction in the context of wide complex tachycardia, an invasive EP study may easily and safely prove or rule out aberrancy.

[Reversible severe cardiomyopathy caused by a slow permanent tachycardia]. / Reversible, schwere Kardiomyopathie als Folge einer langsamen, permanenten Schmalkomplextachykardie.

Incessant narrow QRS complex tachycardias may result in severe tachycardia-induced cardiomyopathy even if the heart rate during tachycardia is only moderately elevated. The risk of ventricular deterioration is particularly increased in patients with underlying congenital heart disease. In these patients, drug treatment is often insufficient. Thus, catheter ablation of the arrhythmogenic substrate is required in the majority of patients. After successful ablation, ventricular function may recover completely.

Recommendations from the Association for European Paediatric and Congenital Cardiology for training in diagnostic and interventional electrophysiology.

The field of electrophysiology (EP) in paediatric cardiology patients and adults with congenital heart disease is complex and rapidly growing. The current recommendations for diagnostic and invasive electrophysiology of the working group for Cardiac Dysrhythmias and Electrophysiology of the Association for European Paediatric and Congenital Cardiology acknowledges the diveristy of European countries and centers. These training recommendations can be fulfilled in a manageable period of time, without compromising the quality of training required to become an expert in the field of paediatric and congenital EP and are for trainees undergoing or having completed accredited paediatric cardiologist fellowship. Three levels of expertise, the training for General paediatric cardiology EP, for non-invasive EP and invasive EP have been defined. This Association for European EP curriculum describes the theoretical and practicsal knowledge in clinical EP; catheter ablation, cardiac implantable electronic devices, inherited arrhythmias and arrhythmias in adults with congenital heart defects for the 3 levels of expertise.

Congenital Lymphatic Malformation and Aortic Aneurysm in a Patient with TSC2 Mutation.

We present a 7-year-old boy with tuberous sclerosis and congenital segmental lymphedema (CSL) of the left leg, as well as two aortic aneurysms. He was treated with everolimus (EVE) since the age of 14 months. His CSL regressed under treatment with EVE. His first aneurysms required operative intervention at age of 17 months. Four months afterward a new aortic aneurysm had been detected above the Dracon graft, but this one remained stable since that time. The patient didn't experience severe side effects. EVE has been well tolerated without disturbance of somatic growth or serious adverse effect.

Value of Regular Defibrillation Threshold Testing After Extracardiac Implantable Cardioverter Defibrillator Placement in Small Children During Mid-Term Follow-Up.

OBJECTIVES: The purpose of this study was to analyze course of defibrillation threshold (DFT) with growth. BACKGROUND: Data on regular DFT testing after extracardiac implantable cardioverter-defibrillator (ICD) placement in infants and small children is still limited. METHODS: An extracardiac ICD was placed in 23 pediatric patients (median age 6.1 years; median body weight 21 kg, median length 120 cm). The defibrillator lead was tunneled pleurally, and the device was placed as "active can" in the right upper abdomen or in a horizontal position between the diaphragm and the pericardium, respectively. DFT was verified intraoperatively, 3 months later, and every 12 months thereafter. The aim was to achieve DFT <15 J allowing ICD programming with a double safety margin above DFT. RESULTS: In all 23 patients, an intraoperative DFT <15 J could be accomplished. Serial DFT testing showed an increase from a median DFT of 10 J intraoperatively to 15 J after 1 year. During mean follow-up of 2.0 years, a significant correlation between DFT and body length, but not body weight, was observed. In 4 of 23 (17%) patients, surgical revision was required because of a DFT increase >20 J during regular DFT testing. No complications regarding DFT testing were noted. CONCLUSIONS: After extracardiac ICD placement in infants and small children, DFT increase related to body length was evident during mid-term follow-up. Routine serial DFT testing was a safe procedure and identified a significant DFT increase in 4 of 23 patients. Serial DFT testing during follow-up in these patients is recommended.

Arrhythmias in congenital heart disease: a position paper of the European Heart Rhythm Association (EHRA), Association for European Paediatric and Congenital Cardiology (AEPC), and the European Society of Cardiology (ESC) Working Group on Grown-up Congenital heart disease, endorsed by HRS, PACES, APHRS, and SOLAECE.

The population of patients with congenital heart disease (CHD) is continuously increasing with more and more patients reaching adulthood. A significant portion of these young adults will suffer from arrhythmias due to the underlying congenital heart defect itself or as a sequela of interventional or surgical treatment. The medical community will encounter an increasing challenge as even most of the individuals with complex congenital heart defects nowadays become young adults. Within the past 20 years, management of patients with arrhythmias has gained remarkable progress including pharmacological treatment, catheter ablation, and device therapy. Catheter ablation in patients with CHD has paralleled the advances of this technology in pediatric and adult patients with structurally normal hearts. Growing experience and introduction of new techniques like the 3D mapping systems into clinical practice have been particularly beneficial for this growing population of patients with abnormal cardiac anatomy and physiology. Finally, device therapies allowing maintanence of chronotropic competence and AV conduction, improving haemodynamics by cardiac resynchronization, and preventing sudden death are increasingly used. For pharmacological therapy, ablation procedures, and device therapy decision making requires a deep understanding of the individual pathological anatomy and physiology as well as detailed knowledge on natural history and long-term prognosis of our patients. Composing expert opinions from cardiology and paediatric cardiology as well as from non-invasive and invasive electrophysiology this position paper was designed to state the art in management of young individuals with congenital heart defects and arrhythmias.

Long-Term Follow-Up After Catheter Ablation of Atrioventricular Nodal Reentrant Tachycardia in Children.

BACKGROUND: Catheter ablation of the slow conducting pathway (SP) is treatment of choice for atrioventricular nodal reentrant tachycardia (AVNRT). Although there are abundant data on AVNRT ablation in adult patients, little is known about the long-term results ≥3 years after AVNRT ablation in pediatric patients. METHODS AND RESULTS: Follow-up data from 241 patients aged ≤18 years who had undergone successful AVNRT ablation were analyzed. Median age at ablation had been 12.5 years, and median follow-up was 5.9 years. Radiofrequency current had been used in 168 patients (70%), whereas cryoenergy had been used in 73 patients (30%). Procedural end point of AVNRT ablation had been either SP ablation (no residual dual atrioventricular nodal physiology) or SP modulation (residual SP conduction allowing for a maximum of one atrial echo beat). After the initial AVNRT ablation, calculated freedom from AVNRT was 96% at 1 year, 94% at 3 years, 93% at 5 years, and 89% at 8 years. Age, sex, body weight, the choice of ablation energy, and the procedural end point of AVNRT ablation did not impact freedom from AVNRT. Six of 22 AVNRT recurrences (27%) occurred ≥5 years after ablation. No late complications including atrioventricular block were noted. CONCLUSIONS: Cumulatively, catheter ablation of AVNRT continued to be effective in >90% of our pediatric patients during the long-term course. A significant part of recurrences occurred >5 years post ablation. Body weight, energy source, and the end point of ablation had no impact on long-term results. No adverse sequelae were noted.

Radiofrequency Catheter Ablation of Accessory Atrioventricular Pathways in Infants and Toddlers ≤ 15 kg.

Accessory atrioventricular pathways (AP) are the most common substrate for paroxysmal supraventricular tachycardia in infants and small children. Up-to-date data on AP ablation in infants and small children are limited. The aim of the present study was to gain additional insight into radiofrequency (RF) catheter ablation of AP in infants and toddlers focusing on efficacy and safety in patients with a body weight of ≤ 15 kg. Since 10/2002, RF ablation of AP was performed in 281 children in our institution. Indications, procedural data as well as success and complication rates in children with a body weight ≤ 15 kg (n = 22) were compared with children > 15 kg (n = 259). Prevalence of structural heart anomalies was significantly higher among children ≤ 15 kg (27 vs. 5.7 %; p = 0.001). Procedure duration (median 262 vs. 177 min; p = 0.001) and fluoroscopy time (median 20.6 vs. 14.0 min; p = 0.007) were significantly longer among patients ≤ 15 kg. Procedural success rate did not differ significantly between the two groups (82 vs. 90 %). More RF lesions were required for AP ablation in the smaller patients (median 12 vs. 7; p = 0.019). Major complication rate was significantly higher in children ≤ 15 kg (9 vs. 1.1 %; p = 0.05) with femoral vessel occlusion being the only major adverse event in patients ≤ 15 kg. Catheter ablation of AP in children was effective irrespective of body weight. In children ≤ 15 kg, however, procedures were more challenging and time-consuming. Complication rate and number of RF lesions in smaller children were higher when compared to older children.

Catheter Ablation of Pediatric Focal Atrial Tachycardia: Ten-Year Experience Using Modern Mapping Systems.

Experience of catheter ablation of pediatric focal atrial tachycardia (FAT) is still limited. There are data which were gathered prior to the introduction of modern 3D mapping and navigation systems into the clinical routine. Accordingly, procedures were associated with significant fluoroscopy and low success rates. The aim of this study was to present clinical and electrophysiological details of catheter ablation of pediatric FAT using modern mapping systems. Since March 2003, 17 consecutive patients <20 years underwent electrophysiological study (EPS) for FAT using the NavX(®) system (n = 7), the non-contact mapping system (n = 6) or the LocaLisa(®) system (n = 4), respectively. Radiofrequency was the primary energy source; cryoablation was performed in selected patients with a focus close to the AV node. In 16 patients, a total number of 19 atrial foci (right-sided n = 13, left-sided n = 6) could be targeted. In the remaining patient, FAT was not present/inducible during EPS. On an intention-to-treat basis, acute success was achieved in 14/16 patients (87.5 %) with a median number of 11 (1-31) energy applications. Ablation was unsuccessful in two patients due to an epicardial location of a right atrial focus (n = 1) and a focus close to the His bundle (n = 1), respectively. Median procedure time was 210 (84-332) min, and median fluoroscopy time was 13.1 (4.5-22.5) min. In pediatric patients with FAT, 3D mapping and catheter ablation provided improved clinical quality of care. Catheter ablation may be considered early in the course of treatment of this tachyarrhythmia in symptomatic patients.

Catheter ablation of pediatric AV nodal reentrant tachycardia: results in small children.

BACKGROUND: AV nodal reentrant tachycardia (AVNRT) is commonly encountered in pediatric patients. Definite treatment can be achieved by catheter ablation. The purpose of the study was to evaluate the efficacy and safety of AVNRT ablation focusing on children with a body weight ≤25 kg. PATIENTS AND RESULTS: Catheter ablation of AVNRT was attempted in 253 patients. Median age was 12.5 years; median body weight was 48.7 kg. 25 (9.9 %) children had a body weight ≤25 kg. Congenital heart disease was present in 6 patients (2.4 %). Procedural success was achieved in 98 % using radiofrequency, in 100 % using cryoenergy alone, and in 94 % using both energy sources. In patients with a body weight ≤25 kg, success was achieved in 96 %. In patients ≤25 kg, fluoroscopy and procedure duration did not differ from those >25 kg. The rate of major complications was significantly higher in the patients ≤25 kg (12 vs. 2.2 %, p = 0.04). Permanent AV block after RF ablation occurred in 2 patients with congenital heart disease and one infant with a body weight of 8.7 kg. CONCLUSIONS: Catheter ablation of AVNRT in children and adolescents was safe and effective. Infants and small children with a body weight ≤25 kg had a higher prevalence of serious complications. This should alert physicians in decision making toward catheter ablation in these patients. In patients with congenital heart disease and different anatomy of the cardiac conduction system, operators must be aware of an increased risk for AV block.

Melody transcatheter valve: Histopathology and clinical implications of nine explanted devices.

OBJECTIVES: We examined interventionally implanted valved Melody conduits after surgical explantation by means of histology and immunohistochemistry and matched these findings with clinical data in order to assess in vivo biocompatibility and to identify risk factors for graft failure. METHODS: 9 Melody valves had been implanted in 8 patients (pulmonary n = 7, tricuspid position n = 1). Indication for explantation included significant obstruction in 7 patients and valve insufficiency in 1 patient. 4 of 8 patients had suffered from endocarditis. Mean interval between implantation and explantation was 3.2 (1.8-5.2) years. All explants were worked up using a uniform protocol with fixation in formalin and embedding in methylmethacrylate. RESULTS: All but one valve of the explanted Melody grafts were thin and histologically intact without any pathological findings. Complete neo-endothelialization could be demonstrated by means of immunohistochemistry. All 4 Melody valves from patients with endocarditis showed dense granulocytic infiltrations, 3 of these showed thrombotic material within the valves. CONCLUSION: This report covers the first series of explanted Melody valves from humans applying a uniform protocol for histopathological examination. Good biocompatibility of the Melody valves could be demonstrated after a mid-term follow-up. Factors for graft failure included endocarditis, outgrowth, and residual stenosis. These findings may have significant implications for the implant procedure as well as care of the patients during long-term follow-up.

[Tachycardiac arrhythmia in children without congenital heart diseases]. / Tachykarde Herzrhythmusstörungen bei Kindern ohne angeborene Herzfehler.

Based on invasive electrophysiological studies and ablation procedures of tachycardias in children and adolescents, the understanding and knowledge of the different tachycardia substrates have significantly increased in recent years. This article describes the underlying pathophysiological mechanisms together with the expected changes in electrocardiogram (ECG) of the four most common types of supraventricular tachycardia in children and adolescents without congenital heart defects: atrioventricular reentrant tachycardia, atrioventricular nodal reentrant tachycardia, focal atrial tachycardia and permanent junctional reentrant tachycardia. Furthermore, idiopathic ventricular tachycardia is described. The incidence, clinical symptoms, natural course and prognosis of each particular tachycardia will be specified . The pharmacological and interventional treatment will be the focus of other reports in this issue. Finally, the current recommendations for the approach to asymptomatic children and adolescents with preexcitation are discussed according to the current guidelines.

Double cryoenergy application (freeze-thaw-freeze) at growing myocardium: lesion volume and effects on coronary arteries early after energy application. Implications for efficacy and safety in pediatric patients.

INTRODUCTION: Data on radiofrequency current application (RFA) at growing myocardium suggest that coronary artery stenosis may occur with a low incidence. Cryoenergy has emerged as an effective alternative to RFA. Although already used in clinical practice, experience with cryoenergy is low due to lack of data concerning effects of a modified double cryoenergy application, a freeze-thaw-freeze cycle, at growing myocardium. Purpose of the study was to assess lesion volume (efficacy) and risk of coronary artery damage (safety) early, 48 hours, after modified double cryoenergy application in a piglet model. METHODS AND RESULTS: In 5 piglets, following selective coronary angiography, two sequential cycles of cryoenergy were delivered at -75 °C for 4 minutes, interrupted by thawing for one minute, at the atrioventricular groove. Piglets were restudied after 48 hours by coronary angiography and intracoronary ultrasound (ICUS). Ablation lesions were examined morphologically and lesion volume was determined by 3-dimensional morphometric analysis. Lesion volume was 109.21 ± 39.61 mm(3) for atrial and 150.30 ± 53.21 mm(3) (P = 0.02) for ventricular lesions. Lesion depth was not significantly different for atrial, 3.07 ± 1.08 mm, versus ventricular lesions, 3.56 ± 1.3 mm. Cryoenergy induced minor coronary artery damage with medial and adventitial necrosis but a preserved intimal layer was present in 2/31 lesions, which had not been detected by coronary angiography or ICUS. CONCLUSION: Early after double cryoenergy application, subclinical minor changes of the coronary artery wall could be detected occasionally whereas the intimal layer remained intact. These findings may have implications on efficacy and safety when cryoenergy is applied for tachycardia substrates in pediatric patients.

Left cardiac sympathetic denervation for the management of life-threatening ventricular tachyarrhythmias in young patients with catecholaminergic polymorphic ventricular tachycardia and long QT syndrome.

BACKGROUND: Left cardiac sympathetic denervation (LCSD) may be a therapeutic adjunct for young patients with catecholaminergic polymorphic ventricular tachycardia (CPVT) and long QT syndrome (LQTS) who are not fully protected by beta-blockade. OBJECTIVE: The objective of this analysis was to report our institutional experience with LSCD in young patients for the management of life-threatening ventricular arrhythmias in CPVT and LQTS. METHODS: Ten young patients with CPVT and LQTS underwent transaxillary LSCD at our institution. Mean age at surgery was 14.0 (range 3.9-42) years, mean body weight was 45.7 (range 15.5-90) kg. Five patients had the clinical diagnosis of CPVT, three were genotype positive for a mutation in the ryanodine-receptor-2-gene. Four of five LQTS patients were genotype positive. Indications for LCSD were recurrent syncope, symptomatic episodes of ventricular tachycardias and/or internal cardioverter-defibrillator (ICD) discharges, and aborted cardiac arrest despite high doses of beta-blockers. RESULTS: LCSD was performed via the transaxillary approach. No significant complications were observed. Two patients already had an ICD, 6 patients received an ICD at the same operation or shortly thereafter. Median length of follow-up after LCSD was 2.3 (range 0.6-3.9) years. After LCSD a marked reduction in arrhythmia burden and cardiac events was observed in all patients while medication was continued. None of the patients had any further ICD discharge for sustained VT. CONCLUSIONS: After LCSD, arrhythmia burden could significantly be reduced in all our young patients with CPVT and LQTS.

The diagnostic and therapeutic aspects of loss-of-function cardiac sodium channelopathies in children.

BACKGROUND: Loss-of-function sodium channelopathies manifest as a spectrum of diseases including Brugada syndrome (BrS) and cardiac conduction disease. OBJECTIVE: To analyze the diagnostic and therapeutic aspects of these disorders in children. METHODS: Patients aged ≤ 16 years with genetically confirmed loss-of-function sodium channelopathies (SCN5A mutation), presenting with cardiac symptoms, positive family history, and/or abnormal electrocardiogram (ECG), were included. Abnormal ECG consisted of type 1 BrS ECG and/or prolonged conduction intervals (PR interval/QRS duration > 98th percentile for age). RESULTS: Among the cohort (n = 33, age 6 ± 5 years, 58% male subjects, 30% probands), 14 (42%) patients were symptomatic, presenting with syncope (n = 5), palpitations (n = 1), supraventricular arrhythmias (n = 3), aborted cardiac arrest (n = 3), and sudden cardiac death (n = 2). Heart rate was 91 ± 26 beats/min, PR interval 168 ± 35 ms, QRS duration 112 ± 20 ms, and heart-rate corrected QT interval 409 ± 26 ms. Conduction intervals were prolonged in 28 (85%) patients; 6 of these patients also had spontaneous type 1 BrS ECG. Eight fever-associated events occurred in 6 patients; 2 of these were vaccination-related fever episodes. Treatment included aggressive antipyretics during fever in all patients; antiarrhythmic treatment included implantable cardioverter-defibrillator (n = 4), pacemaker (n = 2), and beta-blockers, either alone (n = 3) or in combination with device (n = 2). During follow-up (4 ± 4 years), 2 previously symptomatic patients had monomorphic ventricular tachycardia; there were no deaths. CONCLUSIONS: Diagnosis of loss-of-function sodium channelopathies in children relies on cardiac symptoms, family history, and ECG. Fever and vaccination are potential arrhythmia triggers; conduction delay is the commonest finding on ECG. Beta-blockers have a role in preventing tachycardia-induced arrhythmias; implantable cardioverter-defibrillator should probably be reserved for severe cases.

Value of dynamic substrate mapping to identify the critical diastolic pathway in postoperative ventricular reentrant tachycardias after surgical repair of tetralogy of fallot.

UNLABELLED: Characterization of the Critical Isthmus in VT in TOF. INTRODUCTION: The complexity of postoperative ventricular reentrant tachycardias may limit success of catheter ablation. The objective of this analysis was to compare the usefulness of dynamic substrate mapping (DSM) versus color-coded isopotential mapping of the noncontact mapping system for the identification of the critical diastolic pathway of postoperative ventricular reentrant tachycardias (VT) after surgical repair of tetralogy of Fallot (TOF). METHODS: Postoperative VT had been studied applying isopotential maps with the noncontact mapping system EnSite in 7 patients, and radiofrequency current lesion lines had been applied across the shortest isthmus to target during sinus rhythm. Data of the noncontact mapping system were reanalyzed applying the DSM algorithm. For DSM, a 2-Hz filter and color settings between 0 mV and 50% of peak negative voltage (PNV) with autofocus turned off were used. DSM was initially applied over the QRS complex duration during sinus rhythm. Abnormal myocardium was defined as <35-40% of PNV. DSM was subsequently applied to ventricular diastole during the final 33% of VT cycle length. Areas with >70% of PNV within this time frame were to identify the critical diastolic pathway. RESULTS: Applying DSM, the critical diastolic pathway of the VT was identified in all 7 patients that corresponded to the regions targeted for ablation. CONCLUSION: By focusing the time reference to electrical diastole, when the VT wavefront is moving through the low-voltage area, the region of greatest relative voltage could be highlighted, which corresponded to the diastolic pathway. (J Cardiovasc Electrophysiol, Vol. 23, pp. 930-937, September 2012).