Successful caudal vena cava and pulmonary vein isolation in healthy horses using 3D electro-anatomical mapping and a contact force-guided ablation system.

BACKGROUND: Recently, treatment of equine atrial tachycardia by three-dimensional electro-anatomical mapping (3D EAM) and radiofrequency catheter ablation (RFCA) has been described. Myocardial sleeves in the caudal vena cava and pulmonary veins are a potential trigger for initiation and perpetuation of atrial tachycardia and atrial fibrillation in the horse. Isolation of these myocardial sleeves by RFCA may be an effective treatment for these arrhythmias. OBJECTIVES: To describe the feasibility of 3D EAM and RFCA to isolate caudal vena cava and pulmonary veins in adult horses using 3D mapping and a contact force (CF)-guided ablation system. STUDY DESIGN: In vivo experiments. METHODS: 3D EAM and RFCA was performed in five horses without cardiovascular disease under general anaesthesia, using the CF-guided system CARTO®3. Point-by-point RFCA aimed for isolation of caudal vena cava and pulmonary veins. Radiofrequency energy was delivered in power-controlled mode with a target power of 45 W, CF between 10 and 15 g and 30 mL/min irrigation rate, until an ablation-index of 450-500 was reached. RESULTS: In the right atrium, myocardial sleeves of the caudal vena cava were isolated (n = 5). In the left atrium, isolation of ostium II (n = 3), ostium III (n = 1) and ostium I, II and III en bloc (n = 1) was performed. Successful isolation was confirmed by entrance and exit block. MAIN LIMITATIONS: Horses were euthanised at the end of the procedure, so long term effects such as potential reconnection of isolated veins could not be studied. CONCLUSIONS: This is the first description of 3D EAM and RFCA with CARTO®3 in horses, thereby showing the technical feasibility and successful caudal vena cava and pulmonary vein isolation. CF measurement allowed monitoring of catheter-tissue contact, resulting in efficient acute lesion creation as confirmed by entrance and exit block. This is a promising treatment for cardiac arrhythmias in horses.

Three-dimensional electro-anatomical mapping and radiofrequency ablation as a novel treatment for atrioventricular accessory pathway in a horse: A case report.

We describe the diagnosis and treatment of an atrioventricular accessory pathway (AP) in a horse using 3-dimensional electro-anatomical mapping (3D EAM) and radiofrequency catheter ablation (RFCA). During routine evaluation of the horse, intermittent ventricular pre-excitation was identified on the ECG, characterized by a short PQ interval and abnormal QRS morphology. A right cranial location of the AP was suspected from the 12-lead ECG and vectorcardiography. After precise localization of the AP using 3D EAM, ablation was performed and AP conduction was eliminated. Immediately after recovery from anesthesia an occasional pre-excited complex still was observed, but a 24-hour ECG and an ECG during exercise 1 and 6 weeks after the procedure showed complete disappearance of pre-excitation. This case shows the feasibility of 3D EAM and RFCA to identify and treat an AP in horses.

Detection of the origin of atrial tachycardia by 3D electro-anatomical mapping and treatment by radiofrequency catheter ablation in horses.

BACKGROUND: Atrial tachycardia (AT) can be treated by medical or electrical cardioversion but the recurrence rate is high. Three-dimensional electro-anatomical mapping, recently described in horses, might be used to map AT to identify a focal source or reentry mechanism and to guide treatment by radiofrequency ablation. OBJECTIVES: To describe the feasibility of 3D electro-anatomical mapping and radiofrequency catheter ablation to characterize and treat sustained AT in horses. ANIMALS: Nine horses with sustained AT. METHODS: Records from horses with sustained AT referred for radiofrequency ablation at Ghent University were reviewed. RESULTS: The AT was drug resistant in 4 out of 9 horses. In 8 out of 9 horses, AT originated from a localized macro-reentrant circuit (n = 5) or a focal source (n = 3) located at the transition between the right atrium and the caudal vena cava. In these 8 horses, local radiofrequency catheter ablation resulted in the termination of AT. At follow-up, 6 out of 8 horses remained free of recurrence. CONCLUSIONS AND CLINICAL IMPORTANCE: Differentiation between focal and macro-reentrant AT in horses is possible using 3D electro-anatomical mapping. In this study, the source of right atrial AT in horses was safely treated by radiofrequency catheter ablation.

Durable Physiological Changes and Decreased Syncope Burden 12 Months After Unifocal Right-Sided Ablation Under Computed Tomographic Guidance in Patients With Neurally Mediated Syncope or Functional Sinus Node Dysfunction.

[Figure: see text].

Three dimensional ultra-high-density electro-anatomical cardiac mapping in horses: methodology.

BACKGROUND: Ultra-high-density cardiac mapping allows very accurate characterisation of atrial and ventricular electrophysiology and activation timing. OBJECTIVE: To describe the technique and evaluate the feasibility of magnetic electro-anatomical mapping of the equine heart. STUDY DESIGN: In vivo experimental method development. METHODS: A mapping system using an 8.5F bidirectional deflectable catheter with a deployable mini-basket (3-22 mm) containing 64 electrodes divided over eight splines was evaluated. Based upon predefined beat acceptance criteria, the system automatically acquires endocardial electrograms and catheter location information. Electro-anatomical maps were acquired from four horses in sinus rhythm under general anaesthesia. RESULTS: All endocardial areas within each chamber could be reached. Access to the left atrium required the use of a deflectable sheath. With the exception of the left atrial map of horse 1, all four chambers in all four horses could be mapped. Optimisation of the beat acceptance criteria led to a reduction in manual correction of the automatically accepted beats from 13.1% in the first horse to 0.4% of the beats in the last horse. MAIN LIMITATIONS: Only a limited number of horses were included in the study. CONCLUSION: Ultra-high-density 3D electro-anatomical mapping is feasible in adult horses and is a promising tool for electrophysiological research and characterisation of complex arrhythmias.

Treatment patterns in anticoagulant therapy in patients with newly diagnosed atrial fibrillation in Belgium: results from the GARFIELD-AF registry.

Background: AF, anticoagulation, NOACs, changing patterns of prescription. Methods: We describe baseline data and treatment patterns of patients recruited in Belgium in the Global Anticoagulant Registry in the FIELD-Atrial Fibrillation (GARFIELD-AF). Recruitment began when novel oral anticoagulants (NOACs) were introduced and provides a unique picture of changing treatment patterns over time. 1713 patients with a new (≤6 weeks duration) diagnosis of non-valvular atrial fibrillation (NVAF) and at least one investigator-defined stroke risk factor were recruited between May 2012 and August 2016, and will be prospectively followed for at least 2 years. Results: Overall, anticoagulant use in Belgium was higher than in the rest of Europe: 80.1% of patients received an anticoagulant ± antiplatelet (AP) therapy (14.5% on vitamin K antagonists; 65.6% on NOAC), 10.7% AP therapy and 9.3% no antithrombotic therapy. Over time, we observed an increase in anticoagulant use and a decrease in AP use for stroke prevention. NOAC use in Belgium was the highest of Europe at the study start, with many countries catching up later. In high stroke risk patients (CHA2DS2-VASc ≥2), anticoagulants were used in 84.3%, leaving 15.7% unprotected. In low risk patients (CHA2DS2-VASc 0-1) anticoagulants were overused (58.7%). Factor Xa inhibitors were used more frequently than direct thrombin inhibitors. Conclusion: Guideline adherence on stroke prevention was higher in Belgium than in the rest of Europe, and increased over time. NOAC use in Belgium was the highest of Europe at the study start, with many countries catching up later. Possible reasons are discussed. Clinical Trial Registration: http://www.clinicaltrials.gov . Unique identifier: NCT01090362.

Isolation of pulmonary veins using a thermoreactive implantable device with external energy transfer: Evaluation in a porcine model.

BACKGROUND: Pulmonary vein isolation (PVI) is a well-established method for the treatment of symptomatic paroxysmal atrial fibrillation, but is only partly successful with a high rate of electrical reconnection. We introduce a novel technique in which PVI is accomplished by noninvasive heating of a dedicated thermoresponse implant inserted into the pulmonary veins (PV), demonstrated in a porcine model. METHODS: A self-expanding nitinol-based implant was positioned in the common inferior PV of 11 pigs, using a fluoroscopy-guided transatrial appendage approach. Ablation was performed through contactless energy transfer from a primary extracorporal coil to a secondary heat ring (HR) embedded in the proximal part of the implant. Electrophysiological conduction was assessed prior to and postablation, and at 3 months. Histological samples were obtained acutely (n  =  4) and after 3 months (n  =  7). RESULTS: In total, 13 PV implants were successfully positioned in the inferior PVs of 11 animals. Ablation was performed without injury of adjacent structures. PVI and bidirectional block was electrophysiologically confirmed in all cases immediately at the time of implantation and 3 months later in seven chronic animals in whom testing was repeated. Marked evidence of ablation around the proximal HR was evident at 3 months postprocedure, with scar tissue formation and only mild neointimal proliferation. CONCLUSIONS: Successful PVI can be obtained by external electromagnetic heat transfer to a novel pulmonary vein implant.

A preliminary study of pulmonary vein implant applicability and safety as a potential ablation platform in a follow-up study in pigs.

BACKGROUND: Recurrence of atrial fibrillation after an ablation procedure remains a major problem which emphasizes the need for improved pulmonary vein isolation techniques. AIMS: The aim of this study was to describe an implantation procedure of a pulmonary vein-stent which may possibly serve as an ablation technique in the future and to examine stent safety in a follow-up study in pigs. METHODS AND RESULTS: Eight pigs were catheterized and nine self-expanding nitinol stents were implanted through a transfemoral or transatrial approach into the antra of the pulmonary veins. After 3 months' follow-up, the animals were euthanized for further examination. During the follow-up phase, no complications were observed. Absence of thrombus formation or pulmonary vein wall dissection was noticed during anatomical and histological evaluation of the heart-lung packages. All implants were almost completely covered by neo-intima, of which thickness varied between 0.2 and 3.9 mm. CONCLUSIONS: Stents can safely be positioned and deployed into the antra of the pulmonary veins without any acute or long-term (3 months) adverse effects. In the future, these implants could function as a permanently implanted ablation device and provide new therapeutic strategies for pulmonary vein isolation in patients with atrial fibrillation.

A Preclinical Study of an Implanted Device in the Pulmonary Veins, Intended for the Treatment of Atrial Fibrillation in an Ovine Model.

BACKGROUND: Atrial fibrillation is the most frequent arrhythmia in adults of which the interventional cure is hampered by high recurrence rates. Recurrence after ablation is due to an incomplete isolation of the pulmonary veins. A new ablation technique was performed, in the antra of ovine pulmonary veins, by device implantation, which was heated through a wireless heat-generating system. METHODS AND RESULTS: Implants were placed transatrially in the pulmonary veins of sheep. Using a wireless heating system, the energy was afterward transferred through wires to the implanted device according to a defined protocol. The position of the implant and the applied lesions were macroscopically evaluated. Samples of the ablated tissue of the atrio-pulmonary vein junction were histologically and immunohistochemically examined. CONCLUSIONS: Six ablation procedures in four sheep were successfully performed without adverse cardiac reactions. Implantation of the device and the wireless heat generation was feasible. Sufficient heat was produced at the level of the antra of the pulmonary veins to create ablation lesions, which were histologically and immunohistochemically confirmed.

Usefulness of contrast-enhanced cardiac magnetic resonance in identifying the ventricular arrhythmia substrate and the approach needed for ablation.

AIMS: The endocardial vs. epicardial origin of ventricular arrhythmia (VA) can be inferred from detailed electrocardiogram (ECG) analysis. However, despite its clinical usefulness, ECG has limitations. Alternatively, scarred tissue sustaining VAs can be identified by contrast-enhanced cardiac magnetic resonance (ce-CMR). The objective of this study was to determine the clinical value of analysing the presence and distribution pattern of scarred tissue in the ventricles to identify the VA site of origin and the ablation approach required. METHODS AND RESULTS: A ce-CMR study was carried out before the index ablation procedure in a cohort of 80 patients with non-idiopathic VA. Hyper-enhancement (HE) in each ventricular segment was coded as absent, subendocardial, transmural, mid-myocardial, or epicardial. The endocardial or epicardial VA site of origin was also assigned according to the approach needed for ablation. The clinical VA was successfully ablated in 77 (96.3%) patients, all of them showing HE on ce-CMR. In segments with successful ablation of the clinical ventricular tachycardia, HE was absent in 3 (3.9%) patients, subendocardial in 19 (24.7%), transmural in 36 (46.7%), mid-myocardial in 8 (10.4%), and subepicardial in 11 (14.3%) patients. Epicardial ablation of the index VA was necessary in 3 (6.1%) ischaemic and 12 (42.9%) non-ischaemic patients. The presence of subepicardial HE in the successful ablation segment had 84.6% sensitivity and 100% specificity in predicting an epicardial origin of the VA. CONCLUSION: Contrast-enhanced cardiac magnetic resonance is helpful to localize the target ablation substrate of non-idiopathic VA and also to plan the approach needed, especially in non-ischaemic patients.

The usefulness of the consensus clinical diagnostic criteria in Brugada syndrome.

BACKGROUND: Consensus statements were proposed for the diagnosis of Brugada syndrome (BS). The clinical diagnostic criteria were defined as documented ventricular fibrillation or ventricular tachycardia (VT), family history of sudden cardiac death at <45 years, diagnostic ECGs of family members, inducibility of VT during electrophysiological study, syncope or nocturnal agonal respiration. The clinical validation of these criteria is still missing. Methods and results 280 patients (41 ± 18 years, male: 168 pts) with diagnostic coved type I ECG were included. Consensus clinical diagnostic criteria were present in 244 (87%) patients (40 ± 18 y, 142 males). In 36 pts (13% of the 280 pts, 51 ± 12 years, 27 males) consensus clinical diagnostic criteria were not met. Nine patients (25%) presented with spontaneous type I ECG. Ten of the 36 patients (28%) had a history of atrial fibrillation and 13 (36%) had conduction disease on the baseline ECG. In 23 patients (64%) family screening was not performed. Two of the 36 patients had undocumented syncope during follow-up. Univariate analysis showed no significant difference in event free survival between patients with or without consensus clinical diagnostic criteria. CONCLUSIONS: In a significant number of patients with diagnostic ECG pattern the current diagnostic criteria for BS are not met. These patients have frequently spontaneous type I ECG and clinical signs of Brugada syndrome as paroxysmal atrial fibrillation or conduction disturbances. Our results suggest that in patients with a diagnostic type I ECG pattern the current clinical consensus diagnostic criteria have limited added diagnostic value.

Combined endocardial and epicardial catheter ablation in arrhythmogenic right ventricular dysplasia incorporating scar dechanneling technique.

BACKGROUND: Ventricular tachycardia (VT) ablation in patients with arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C) has a low success rate. A more extensive epicardial (Epi) arrhythmogenic substrate could explain the low efficacy. We report the results of combined endocardial (Endo) and Epi VT ablation and conducting channel (CC) elimination. METHODS AND RESULTS: Eleven consecutive patients with ARVD/C were included in the study. A high-density 3D Endo (321±93 sites mapped) and Epi (302±158 sites mapped) electroanatomical voltage map was obtained during sinus rhythm to define scar areas (<1.5 mV) and CCs inside the scars, between scars, or between the tricuspid annulus and a scar. The end point of the ablation procedure was the elimination of all identified CCs (scar dechanneling) and the abolition of all inducible VTs. The mean procedure and fluoroscopy time were 177±63 minutes and 20±8 minutes, respectively. Epi scar area was larger in all cases (26±18 versus 94±45 cm(2), P<0.01). The combined Endo and Epi VT ablation eliminated all clinical and induced VTs, and the addition of scar dechanneling resulted in noninducibility in all cases. Seven patients continued on sotalol. During a median follow-up of 11 months (6-24 months), only 1 (9%) patient had a VT recurrence. There was a single major bleeding event that did not preclude a successful procedure. CONCLUSIONS: Combined Endo and Epi mapping reveals a wider Epi VT substrate in patients with ARVD/C with clinical VTs. As a first-line therapy, combined Endo and Epi VT ablation incorporating scar dechanneling achieves a very good short- and midterm success rate.

The value of a family history of sudden death in patients with diagnostic type I Brugada ECG pattern.

AIMS: We sought to investigate the value of a family history of sudden death (SD) in Brugada syndrome (BS). METHODS AND RESULTS: Two hundred and eighty consecutive patients (mean age: 41 ± 18 years, 168 males) with diagnostic type I Brugada ECG pattern were included. Sudden death occurred in 69 (43%) of 157 families. One hundred and ten SDs were analysed. During follow-up VF (ventricular fibrillation) or SD-free survival rate was not different between patients with or without a family history of SD of a first-degree relative, between patients with or without a family history of multiple SD of a first-degree relative at any age and between patients with or without a family history of SD in first-degree relatives ≤35 years. One patient had family history of SD of two first-degree relative ≤35 years with arrhythmic event during follow-up. In univariate analysis male gender (P = 0.01), aborted SD (P < 0.001), syncope (P = 0.04), spontaneous type I ECG (P < 0.001), and inducibility during electrophysiological (EP) study (P < 0.001) were associated with worse prognosis. The absence of syncope, aborted SD, spontaneous type I ECG, and inducibility during EP study was associated with a significantly better prognosis (P < 0.001). CONCLUSION: Family history of SD is not predictive for future arrhythmic events even if considering only SD in first-degree relatives or SD in first-degree relatives at a young age. The absence of syncope, aborted SD, spontaneous type I ECG, and inducibility during EP study is associated with a good five-year prognosis.

Number of electrocardiogram leads displaying the diagnostic coved-type pattern in Brugada syndrome: a diagnostic consensus criterion to be revised.

AIMS: According to the diagnostic consensus criteria, the electrocardiographic (ECG) diagnosis of Brugada syndrome requires coved-type > or =2 mm ST-segment elevation in >1 right precordial lead (RPL) V1-V3 in the presence or absence of a sodium-channel blocker. However, this consensus has not been evaluated. We aimed to assess the distribution of coved-type ST-segment elevation on RPLs in a large patient cohort to reevaluate the appropriateness of the diagnostic consensus criteria. METHODS AND RESULTS: We included 186 individuals with spontaneous and/or drug-induced ECGs of coved-type > or =2 mm ST-segment elevation in at least one RPL. A total of 376 ECGs were analysed for the number, distribution and maximal J-point elevation of diagnostic RPLs. Among all ECGs, 27 (7%) showed a coved-type pattern in 3 RPLs, 205 (55%) in 2 RPLs, and 144 (38%) in only 1 RPL. Leads V1 and V2 were diagnostic in 99% of all ECGs with two diagnostic RPLs. Lead V3 alone was not diagnostic in any ECG. Maximal J-point elevation was significantly higher in lead V2 than V1. Sixty case subjects (32%) had only ECGs with one RPL displaying a coved-type ST-segment elevation. There was no significant difference in clinical presentation and outcome compared with the 126 Brugada patients with ECGs displaying >1 diagnostic RPL. Major arrhythmic events occurred with the same rate (8%) in both groups during a follow-up >5 years. CONCLUSION: Lead V3 does not yield diagnostic information in Brugada syndrome. Individuals with ECGs displaying only one diagnostic RPL have a similar clinical profile and arrhythmic risk as Brugada patients with ECGs displaying >1 diagnostic RPL. Revision of the consensus criteria should be considered.

Genetic basis of ventricular arrhythmias.

Sudden cardiac death caused by malignant ventricular arrhythmias is the most important cause of death in the industrialized world. Most of these lethal arrhythmias occur in the setting of ischemic heart disease. A significant number of sudden deaths, especially in young individuals, are caused by inherited ventricular arrhythmic disorders, however. Genetically induced ventricular arrhythmias can be divided in two subgroups: the primary electrical disorders or channelopathies, and the secondary arrhythmogenic cardiomyopathies. This article focuses on the genetic background of these electrical disorders and the current knowledge of genotype-phenotype interactions.

Inferior and lateral electrocardiographic repolarization abnormalities in Brugada syndrome.

BACKGROUND: Repolarization abnormalities in the inferior-lateral leads in Brugada syndrome (BS) have not been systematically investigated. METHODS AND RESULTS: 280 patients (age, 41+/-18 years; 168 males) with BS were screened for inferior-lateral repolarization abnormalities. The repolarization abnormalities were classified either as early repolarization pattern or coved > or = 2-mm Brugada pattern and as spontaneous or class I antiarrhythmic drug (AAD) induced. Thirty-two patients (11%) had inferior-lateral spontaneous early repolarization pattern. These patients were less likely to be asymptomatic at first presentation (13 of 32 versus 156 of 248 patients, P=0.02), and spontaneous type I ECG was more frequent among them (38% versus 21%, P=0.05). The spontaneous early repolarization pattern occurred more frequently among patients with BS than in 283 family members not having BS (11% versus 6%, P=0.03). Class I AAD administration provoked inferior-lateral coved Brugada pattern in 13 patients with BS. These patients had longer baseline PR intervals (206+/-48 versus 172+/-31 ms, P<0.001) and class I AAD-induced QRS interval prolongation (108 to 178 versus 102 ms to 131 ms, P<0.001). In 3 patients, the class I AAD-provoked coved Brugada pattern was only present in the inferior leads. CONCLUSIONS: Inferior-lateral early repolarization pattern occurs spontaneously relatively frequently in BS. These patients have a more severe phenotype. Class I AAD administration provokes inferior-lateral coved Brugada pattern in 4.6% of patients. We report for the first time 3 patients in whom the class I AAD-provoked coved Brugada pattern was only observed in the inferior leads.

Leaving out control groups: an internal contrast analysis of gene expression profiles in atrial fibrillation patients--a systems biology approach to clinical categorization.

Atrial fibrillation (AF) is a frequent chronic dysrythmia with an incidence that increases with age (>40). Because of its medical and socio-economic impacts it is expected to become an increasing burden on most health care systems. AF is a multi-factorial disease for which the identification of subtypes is warranted. Novel approaches based on the broad concepts of systems biology may overcome the blurred notion of normal and pathological phenotype, which is inherent to high throughput molecular arrays analysis. Here we apply an internal contrast algorithm on AF patient data with an analytical focus on potential entry pathways into the disease. We used a RMA (Robust Multichip Average) normalized Affymetrix micro-array data set from 10 AF patients (geo_accession #GSE2240). Four series of probes were selected based on physiopathogenic links with AF entryways: apoptosis (remodeling), MAP kinase (cell remodeling), OXPHOS (ability to sustain hemodynamic workload) and glycolysis (ischemia). Annotated probe lists were polled with Bioconductor packages in R (version 2.7.1). Genetic profile contrasts were analysed with hierarchical clustering and principal component analysis. The analysis revealed distinct patient groups for all probe sets. A substantial part (54% till 67%) of the variance is explained in the first 2 principal components. Genes in PC1/2 with high discriminatory value were selected and analyzed in detail. We aim for reliable molecular stratification of AF. We show that stratification is possible based on physiologically relevant gene sets. Genes with high contrast value are likely to give pathophysiological insight into permanent AF subtypes.

Variability of the diagnostic ECG pattern in an ICD patient population with Brugada syndrome.

INTRODUCTION: The spontaneous presence of a coved-type ECG is considered as an important risk factor in Brugada syndrome. However, diagnosis making and risk stratification may be hampered by the dynamic nature of the ECG abnormalities. The objective of this study was to determine the variability and predictive value of the electrocardiogram in Brugada patients implanted with a cardioverter-defibrillator (ICD). METHODS AND RESULTS: We analyzed consecutive 12-lead ECGs from 89 ICD patients (44 +/- 14 years, 69 males) with Brugada syndrome. A total of 1,161 ECGs were included for analysis (13 +/- 8 ECGs/patient). Twenty-four percent of the ECGs/patient were coved-type I, 25% saddleback-type II or III, and 51% normal. Fifty-seven patients had a diagnostic coved-type ECG spontaneously (group A), 32 patients only after drug challenge (group B). In group A, 38% of the ECGs/patient were diagnostic, 25% saddleback-type, and 37% normal. Fifty-five group A patients (96%) had transient normalization and/or conversion to saddleback-type ECGs. During a mean follow-up of 48 +/- 35 months, 16 patients (18%) experienced appropriate shocks. All patients with appropriate shocks had spontaneous diagnostic ECGs. They tended to have more coved-type ECGs (36 vs 22%, respectively, P = 0.05) than patients without appropriate shocks. CONCLUSIONS: Analysis of serial ECG recordings in an ICD patient population shows that the Brugada-ECG pattern is highly variable over time. In patients with spontaneous coved-type ECG, only every third ECG is diagnostic and every third ECG normal. Patients with spontaneous coved-type ST-segment elevation have a high incidence of appropriate shocks. Spontaneous saddleback-type electrocardiograms are not helpful for risk stratification.