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1.
Europace ; 25(11)2023 11 02.
Article in English | MEDLINE | ID: mdl-37816150

ABSTRACT

AIMS: Patients with systemic right ventricles are at high risk of sudden cardiac death. Arrhythmia is a significant risk factor. Routine Holter monitoring is opportunistic with poor adherence. The aim of this study was to determine if continuous rhythm monitoring with an implantable loop recorder (ILR) could allow early detection of clinically important arrhythmias. METHODS AND RESULTS: Implantable loop recorder implantation was offered to patients with atrial switch repair for transposition of the great arteries. Recordings were made with symptoms or, automatically for pauses, significant bradycardia or tachycardia and reviewed by the multi-disciplinary team. Twenty-four out of 36 eligible patients underwent ILR implantation with no complication. Forty-two per cent had preserved ventricular function, 75% were NYHA functional class I, 88% had low sudden cardiac death risk, 33% had previous intra-atrial re-entrant tachycardia (IART), and none had known conduction disease. Eighteen out of 24 (75%) patients made 52 recordings (52% automated) over 39.5 months (1.6-72.5). Thirty-two out of 52 (62%) recordings in 15/24 (63%) of the cohort were clinically significant and included sinus node disease (two patients), atrioventricular block (two patients), IART (seven patients), and IART with sinus node disease or atrioventricular block (four patients). Implantable loop recorder recordings prompted medication change in 11 patients [beta-blockers (n = 9), anti-coagulation (n = 5), and stopping anti-coagulation (n = 1)] and device therapy recommendation in seven patients [five pacemakers (three: atrioventricular block) and two defibrillators]. Two patients declined intervention; one suffered an arrhythmic death. Intra-atrial re-entrant tachycardia and clinically relevant conduction disease were detected in patients irrespective of sudden cardiac death risk. CONCLUSION: Continuous monitoring with an ILR in patients with systemic right ventricle following atrial switch detects clinically relevant arrhythmias that impact decision-making. In this cohort, clinically relevant arrhythmias did not correlate with sudden cardiac death risk.


Subject(s)
Atrial Fibrillation , Atrioventricular Block , Tachycardia, Supraventricular , Transposition of Great Vessels , Humans , Heart Ventricles/surgery , Atrial Fibrillation/complications , Atrioventricular Block/complications , Sick Sinus Syndrome/complications , Transposition of Great Vessels/complications , Tachycardia , Electrocardiography, Ambulatory , Tachycardia, Supraventricular/therapy , Death, Sudden, Cardiac/etiology , Death, Sudden, Cardiac/prevention & control
2.
J Cardiovasc Electrophysiol ; 31(11): 3061-3063, 2020 11.
Article in English | MEDLINE | ID: mdl-32889746

ABSTRACT

We describe a 47-year-old woman with ischemic ventricular tachycardia (VT) with repetitive implantable cardioverter-defibrillator shocks, requiring ablation. Preprocedural computed tomography (CT) demonstrated a single anatomical channel on the inferior-basal infarcted area between less than a 3-mm wall-thinning area and the mitral annulus, which suggested the circuit of two VTs observed. In addition, distribution of less than 2 mm and less than 3 mm wall-thinning area can explain the mechanism of the variation of the QRS morphology and S-QRS interval during entrainment. Ablation in this region resulted in no VT inducibility and the absence of any VTs for 2 years. CT wall thinning data may allow us to understand the mechanism and circuit of VT and aid VT ablation procedures.


Subject(s)
Catheter Ablation , Defibrillators, Implantable , Tachycardia, Ventricular , Female , Humans , Middle Aged , Tachycardia, Ventricular/diagnostic imaging , Tachycardia, Ventricular/etiology , Tachycardia, Ventricular/surgery , Tomography , Tomography, X-Ray Computed
3.
J Cardiovasc Electrophysiol ; 31(7): 1640-1648, 2020 07.
Article in English | MEDLINE | ID: mdl-32437007

ABSTRACT

BACKGROUND: No study to date has used high-density mapping to investigate the relationship between prior radiofrequency (RF) lesions for persistent atrial fibrillation (PsAF) ablation and subsequent atrial tachycardias (ATs). METHODS: From 41 consecutive patients who underwent AT ablation at a second procedure using an ultrahigh-density mapping system, 22 patients (38 ATs) were included as they also had complete maps with a multipolar catheter and three-dimensional (3D) mapping system at the time of the first PsAF ablation procedure. We, therefore, compared voltage maps from the first AF ablation procedure to those from the subsequent AT ablation procedure, as well as the lesion sets used for AF ablation vs the activation patterns in AT during the second procedure. RESULTS: In the 38 ATs, 211 of 285 analyzed atrial areas displayed low voltage area (LVA) (74%). Eighteen percent (38/211) existed before the index ablation for AF while 82% (173/211) were newly identified as LVA during the second procedure. Ninety-nine percent (172/173) of the newly developed LVA colocalized with RF lesions delivered for PsAF. Of the 38 ATs, 89.5% (34/38) AT circuits were associated with newly developed LVA due to RF lesions whilst 10.5% (4/38) AT circuits were associated with pre-existing LVA observed at the index procedure. No AT circuit was completely independent from index RF lesions in this series. CONCLUSIONS: Analysis of detailed 3D electroanatomical mapping demonstrates that most ATs after PsAF ablation are involving LVAs due to index RF lesions.


Subject(s)
Atrial Fibrillation , Catheter Ablation , Tachycardia, Supraventricular , Atrial Fibrillation/diagnosis , Atrial Fibrillation/surgery , Catheter Ablation/adverse effects , Electrophysiologic Techniques, Cardiac , Humans , Tachycardia, Supraventricular/diagnosis , Tachycardia, Supraventricular/surgery , Treatment Outcome
4.
Europace ; 22(8): 1252-1260, 2020 08 01.
Article in English | MEDLINE | ID: mdl-32594180

ABSTRACT

AIMS: We hypothesized that an epicardial approach using ethanol infusion in the vein of Marshall (EIVOM) may improve the result of ablation for perimitral flutter (PMF). METHODS AND RESULTS: We studied 103 consecutive patients with PMF undergoing high-resolution mapping. The first 71 were treated with radiofrequency (RF) ablation alone (RF-group), and the next 32 underwent EIVOM followed by RF on the endocardial and epicardial mitral isthmus (EIVOM/RF-group). Contact force was not measured during ablation. Acute and 1-year outcomes were compared. Flutter termination rates were similar between the RF-group (63/71, 88.7%) and EIVOM/RF-group (31/32, 96.8%, P = 0.27). Atrial tachycardia (AT) terminated with EIVOM alone in 22/32 (68.6%) in the EIVOM/RF-group. Bidirectional block of mitral isthmus was always achieved in the EIVOM/RF-group, but significantly less frequently achieved in the RF-group (62/71, 87.3%; P = 0.05). Median RF duration for AT termination/conversion was shorter [0 (0-6) s in the EIVOM/RF-group than 312 (55-610) s in the RF-group, P < 0.0001], as well as for mitral isthmus block in the EIVOM/RF-group [246 (0-663) s] than in the RF-group [900 (525-1310) s, P < 0.0001]. Pericardial effusion was observed in 1/32 (3.2%) in EIVOM/RF-group and 5/71 (7.0%) in RF-group (P = 0.66); two in RF-group required drainage and one of them developed subsequent ischaemic stroke. One-year follow-up demonstrated fewer recurrences in the EIVOM/RF-group [6/32 (18.8%)] than in the RF-group [29/71 (40.8%), P = 0.04]. By multivariate analysis, only EIVOM was significantly associated with less AT recurrence (hazard ratio = 0.35, P = 0.018). CONCLUSION: Ethanol infusion in the vein of Marshall may reduce RF duration required for PMF termination as well as for mitral isthmus block without severe complications, and the mid-term outcome may be improved by this approach.


Subject(s)
Atrial Fibrillation , Atrial Flutter , Brain Ischemia , Catheter Ablation , Stroke , Atrial Fibrillation/surgery , Atrial Flutter/diagnosis , Atrial Flutter/drug therapy , Atrial Flutter/surgery , Ethanol , Humans , Treatment Outcome
5.
J Cardiovasc Electrophysiol ; 30(1): 47-57, 2019 01.
Article in English | MEDLINE | ID: mdl-30288830

ABSTRACT

BACKGROUND: Ablation strategies have been developed to improve outcomes in patients with persistent atrial fibrillation (PsAF). However, the impact of atrial fibrillation (AF) termination on late AF recurrence is not well known. The aim of our study was to evaluate the impact of AF termination to atrial tachycardia (AT) or sinus rhythm (SR) during catheter ablation on late AF recurrence after the 3-month blanking period. METHODS AND RESULTS: We prospectively recruited 140 patients (mean age: 58.5 ± 12.3 years old, 74.3% males) with uninterrupted PsAF of a mean duration of 3.7 months. Pulmonary vein antral isolation (PVAI) was the first ablation step, and if AF did not terminate (to SR or AT), we ablated low-voltage areas less than 0.4 mV with specific electrogram characteristics. We successfully converted AF to AT or SR in 56 patients (40%) during PVAI (n = 24) or low-voltage ablation ( n = 32). The remaining 84 patients (60%) were electrically cardioverted to SR at the end of the procedure. One hundred patients (71.4%) maintained SR after a single procedure during a mean follow-up of 21.1 ± 0.8 months. Of the 56 patients with AF termination, 46 (82.1%) had no recurrence, while in the group of 84 patients without AF termination, 54 patients (64.3%) remained in SR ( P < 0.02). CONCLUSION: Ablation of PVAI and specific electrograms in low-voltage areas less than 0.4 mV can lead to encouraging outcomes with a low recurrence rate as well as a lower need for redo procedures.


Subject(s)
Atrial Fibrillation/surgery , Catheter Ablation , Electrophysiologic Techniques, Cardiac , Pulmonary Veins/surgery , Action Potentials , Aged , Atrial Fibrillation/diagnosis , Atrial Fibrillation/physiopathology , Catheter Ablation/adverse effects , Female , Heart Rate , Humans , Male , Middle Aged , Predictive Value of Tests , Prospective Studies , Pulmonary Veins/physiopathology , Recurrence , Risk Factors , Time Factors , Treatment Outcome
6.
J Cardiovasc Electrophysiol ; 30(2): 195-204, 2019 02.
Article in English | MEDLINE | ID: mdl-30288836

ABSTRACT

BACKGROUND: The relationship between the local electrograms (EGMs) and wall thickness (WT) heterogeneity within infarct scars has not been thoroughly described. The relationship between WT and voltages and substrates for ventricular tachycardia (VT) was examined. METHODS: In 12 consecutive patients with myocardial infarction and VT, WT, defined by a multidetector computed tomography, and voltage were compared. In multicomponent EGMs, amplitudes of both far- and near-field components were manually measured, and the performance of the three-dimensional-mapping system automatic voltage measurement was assessed. RESULTS: Of 15 748 points acquired, 2677 points within 5 mm of the endocardial surface were analyzed. In total, 909 (34.0%) multicomponent EGMs were identified; 785 (86.4%) and 883 (97.1%) were distributed in the WT less than 4 and 5 mm, respectively. Far-field EGM voltages increased linearly from 0.14 mV (0.08-0.28 mV) in the WT: 0 to 1 mm to 0.70 mV (0.43-2.62 mV) in the WT: 4 to 5 mm (ρ = 0.430; P < 0.001), and a significant difference was demonstrated between any two WT-groups (P ≤ 0.001). In contrast, near-field EGM voltages varied from 0.27 mV (0.11-0.44 mV) in the WT: 0 to 1 mm to 0.29 mV (0.17-0.53 mV) in the WT: 4 to 5 mm with a poorer correlation (ρ = 0.062, P = 0.04). The proportion of points where the system automatically measured the voltage on near-field EGMs increased from less than 10% in areas of WT: 4 to 5 mm to 50% in areas less than 2 mm. Of 21 VTs observed, seven hemodynamically stable VTs were mapped and terminated in WT: 1 to 4 mm area. CONCLUSIONS: Although far-field voltages gradually increase with the WT, near-field does not. The three-dimensional-mapping system preferentially annotates the near-field components in thinner areas (center of the scar) and the far-field component in thicker areas when building a voltage map. Critical sites of VT are distributed in WT: 1 to 4 mm areas.


Subject(s)
Action Potentials , Cicatrix/diagnostic imaging , Electrophysiologic Techniques, Cardiac , Heart Ventricles/diagnostic imaging , Multidetector Computed Tomography , Myocardial Infarction/diagnostic imaging , Tachycardia, Ventricular/diagnosis , Adult , Aged , Aged, 80 and over , Catheter Ablation , Cicatrix/complications , Cicatrix/physiopathology , Female , Heart Ventricles/physiopathology , Heart Ventricles/surgery , Humans , Male , Middle Aged , Myocardial Infarction/complications , Myocardial Infarction/physiopathology , Predictive Value of Tests , Risk Assessment , Risk Factors , Tachycardia, Ventricular/etiology , Tachycardia, Ventricular/physiopathology , Tachycardia, Ventricular/surgery
7.
J Cardiovasc Electrophysiol ; 30(9): 1443-1451, 2019 09.
Article in English | MEDLINE | ID: mdl-31187516

ABSTRACT

BACKGROUND: Ethanol infusion of the vein of Marshall (VOM) may be effective to treat Marshall bundle-related atrial tachycardia (MB-AT). However, methods and clinical results of ethanol infusion for MB-AT have been not established. OBJECTIVE: To assess the accessibility of the VOM and the success rate of ethanol infusion using a femoral approach for MB-AT. METHODS: A single-center observational study included consecutive patients who had MB-AT and in whom we attempted to treat MB-AT during AT by ethanol infusion. When the VOM was able to be cannulated following VOM venogram using a femoral approach, we systematically performed ethanol infusion with selective balloon occlusion of the VOM. We analyzed in detail the efficacy of ethanol infusion of VOM in patients who were in MB-AT during ethanol infusion. RESULTS: We enrolled 54 consecutive patients in whom we attempted to treat MB-AT by ethanol infusion. Of those, the VOM was accessible in 92.5% of patients (50 of 54). Of the 50 patients treated by ethanol infusion during MB-AT, AT was successfully terminated in 56% percent of the patients (28 of 50) by solo treatment of ethanol infusion without RF ablation. The remainder required additional RF application to terminate the MB-AT. A mean of 6.2 ± 2.8 mL of ethanol was infused resulting in the low-voltage area significantly larger than that before ethanol infusion (12.7 ± 8.3 vs 6.6 ± 5.3 cm2 , P < .001). CONCLUSION: The present study demonstrated that the VOM was highly accessible and MB-AT was amenable to treatment by ethanol infusion by using a femoral approach.


Subject(s)
Atrial Fibrillation/surgery , Catheter Ablation/adverse effects , Catheterization, Peripheral , Coronary Vessels/physiopathology , Ethanol/administration & dosage , Femoral Vein , Pericardium/physiopathology , Tachycardia, Supraventricular/therapy , Action Potentials , Aged , Atrial Fibrillation/diagnosis , Atrial Fibrillation/physiopathology , Catheterization, Peripheral/adverse effects , Coronary Vessels/diagnostic imaging , Ethanol/adverse effects , Female , Heart Rate , Humans , Infusions, Intravenous , Male , Middle Aged , Punctures , Tachycardia, Supraventricular/diagnosis , Tachycardia, Supraventricular/etiology , Tachycardia, Supraventricular/physiopathology , Treatment Outcome
8.
J Cardiovasc Electrophysiol ; 30(9): 1644-1651, 2019 09.
Article in English | MEDLINE | ID: mdl-31347223

ABSTRACT

BACKGROUND: Radiofrequency (RF) ablation is an established treatment for ventricular tachycardia (VT). However, the inability of current RF catheters to address deep or large substrate may explain most of the clinical failures. OBJECTIVES: The aim of this study is to assess the efficacy and safety of ablation in the left ventricle (LV) in sheep using a novel 8-Fr deflectable ablation catheter (Sphere-9; Affera, Inc) with a 9-mm expandable spherical monopolar irrigated RF tip vs a standard RF irrigated catheter (Biosense Webster, Diamond Bar, CA). The impact on tissue was assessed on local bipolar electrograms (from nine uniformly distributed mini surface electrodes and an internal central reference electrode), as well as on direct lesion measurement post mortem. METHODS AND RESULTS: Eleven sheep underwent LV endocardial ablation in healthy tissue using the Sphere-9 catheter (n = 6), or a conventional irrigated RF catheter (n = 5). Twenty lesions were created with the Sphere-9 (current limit: 2.7 A; temp. limit: 60°C; irrigation: 30 mL/min; and duration: 60-120 seconds). Local bipolar electrograms at the surface of the catheter disappeared during RF delivery in 17 of 20 (85%) lesions. The mean lesion volume was 1707 ± 771 mm 3 (length: 15.8 ± 3.3 mm; width: 11.6 ± 4.2 mm; and depth: 10.3 ± 2.9 mm). Twenty-five lesions were created with a standard RF irrigated catheter (power control 35 W; irrigation: 30 mL/min; duration: 60 seconds; volume 537 ± 398 mm 3 ; length: 8.2 ± 2.3 mm; width: 5.2 ± 1.8 mm; and depth: 5.5 ± 2.4 mm). The novel spherical RF catheter created significantly larger lesions ( P < .001 for measurements in all dimensions). There were no steam pops with the novel ablation catheter vs one with the conventional catheter. CONCLUSIONS: This novel spherical monopolar irrigated RF catheter creates lesions that are twice as large and deep as a standard irrigated RF catheter.


Subject(s)
Cardiac Catheterization/instrumentation , Cardiac Catheters , Catheter Ablation/instrumentation , Heart Ventricles/surgery , Therapeutic Irrigation/instrumentation , Action Potentials , Animals , Cardiac Catheterization/adverse effects , Catheter Ablation/adverse effects , Electrophysiologic Techniques, Cardiac , Equipment Design , Female , Heart Ventricles/pathology , Heart Ventricles/physiopathology , Humans , Models, Animal , Sheep, Domestic , Therapeutic Irrigation/adverse effects , Time Factors
9.
Europace ; 21(Supplement_1): i27-i33, 2019 Jan 01.
Article in English | MEDLINE | ID: mdl-30801128

ABSTRACT

Successful mapping and ablation of ventricular tachycardias remains a challenging clinical task. Whereas conventional entrainment and activation mapping was for many years the gold standard to identify reentrant circuits in ischaemic ventricular tachycardia ablation procedures, substrate mapping has become the cornerstone of ventricular tachycardia ablation. In the last decade, technology has dramatically improved. In parallel to high-density automated mapping, cardiac imaging and image integration tools are increasingly used to assess the structural ventricular tachycardia substrate. The aim of this review is to describe the technologies underlying these new mapping systems and to discuss their possible role in providing new insights into identification and visualization of reentrant tachycardia mechanisms.


Subject(s)
Cardiac Imaging Techniques , Catheter Ablation/methods , Electrophysiologic Techniques, Cardiac/methods , Heart Conduction System/anatomy & histology , Tachycardia, Ventricular/diagnosis , Tachycardia, Ventricular/surgery , Humans
10.
J Cardiovasc Electrophysiol ; 29(9): 1197-1206, 2018 09.
Article in English | MEDLINE | ID: mdl-29858882

ABSTRACT

INTRODUCTION: Successful catheter ablation is limited by both poor spatial resolution of abnormal local signals and inability to deliver an effective lesion due to poor tissue contact. We report first worldwide use of the Intellanav MiFi OI catheter (Boston Scientific), providing ultra-high density mapping and incorporating a "DirectSense" algorithm to measure local tissue impedance (LI). METHODS AND RESULTS: 31 patients (65±6 years, 20 male) underwent ablation. LI from the catheter, generator impedance (GI) and maximum electrogram amplitude were recorded in the blood pool, and in regions from healthy to dense scar before, during and after ablation. The catheter demonstrated clear nearfield signal where standard bipolar recordings included farfield signal. LI was lower in dense scar than either healthy tissue or blood pool, and demonstrated an exponential relationship with maximum electrogram amplitude. Maximum LI drop on ablation linearly correlated with initial LI. The median LI drop for successful lesions, resulting in lack of local tissue capture, was 16.0Ω (12.1-19.8 Ω) for LV and 14.6 Ω (10.0-18.3 Ω) for LA, which was larger than for unsuccessful lesions (LV: 9.4 Ω [5.4-15.6 Ω] P = 0.001; LA: 6.8 Ω [4.7-13.0 Ω], P = 0.049). LI percentage drop was also significantly larger for successful than unsuccessful lesions (LV: 17.1 Ω [14.0-19.6 Ω] vs. 10.6 Ω (7.1-16.5 Ω) P = 0.002; LA: 14.2 Ω [10.8-19.5 Ω] vs. 7.5Ω [5.1-11.0 Ω], P = 0.005). CONCLUSION: This novel catheter gives reproducible recordings of local impedance, which are dependent on scar level. Absolute LI drop, and also percentage drop, on ablation may give an indication of tissue contact and subsequent effective lesion formation.


Subject(s)
Atrial Fibrillation/physiopathology , Atrial Fibrillation/surgery , Catheter Ablation/methods , Electrocardiography/methods , Tachycardia, Ventricular/physiopathology , Tachycardia, Ventricular/surgery , Aged , Atrial Fibrillation/diagnosis , Electric Impedance/therapeutic use , Female , Humans , Male , Middle Aged , Tachycardia, Ventricular/diagnosis
11.
Article in English | MEDLINE | ID: mdl-29737045

ABSTRACT

Pacemaker-induced arrhythmias represent a very rare complication. Algorithm-induced ventricular tachycardias have been described but this report is the first to describe a ventricular fibrillation caused by transient undersensing of the ventricular lead during an abdominal ultrasound.

12.
J Cardiovasc Electrophysiol ; 28(12): 1393-1402, 2017 Dec.
Article in English | MEDLINE | ID: mdl-28884923

ABSTRACT

INTRODUCTION: We aimed to evaluate the extent of atrial fibrosis in paroxysmal atrial fibrillation (AF) and the correlation with ablation outcomes after pulmonary vein antral isolation (PVΑI) using a mapping system with high-resolution and high-spatial sampling. METHODS AND RESULTS: We prospectively enrolled 80 consecutive patients (45 males, median age 60.26 years) with symptomatic paroxysmal AF who were scheduled for PVAI. Prior to PVAI, high-density bipolar voltage mapping (median number of 2,485 points) was carried out during sinus rhythm in all patients. Criteria for an adequate left atrium (LA) shell were > 2,000 points. Each acquired point was classified according to the peak-to-peak bipolar voltage electrogram based on two criteria (criterion A: healthy > 0.8 mV, border zone: 0.4-0.8 mV and scarred: < 0.4 mV, criterion Β: healthy: > 0.5 mV, border zone: 0.25-0.5 mV and scarred: < 0.25 mV). The extent of low-voltage area < 0.4 mV significantly predicted atrial tachyarrhythmia recurrence after the blanking period (P = 0.002). In univariate analysis, the presence of LA voltage areas < 0.4 mV more than 10% of the total surface area was the only significant predictor of arrhythmia recurrence. The analysis based on window B cutoff values failed to demonstrate any predictors of arrhythmia recurrence. CONCLUSION: These data demonstrate that the existence of LA voltage areas < 0.4 mV more than 10% of the total LA surface area predicts arrhythmia recurrence following PVAI for paroxysmal AF.


Subject(s)
Atrial Fibrillation/diagnostic imaging , Atrial Fibrillation/physiopathology , Body Surface Potential Mapping/methods , Catheter Ablation/methods , Imaging, Three-Dimensional/methods , Aged , Atrial Fibrillation/surgery , Female , Follow-Up Studies , Humans , Male , Middle Aged , Predictive Value of Tests , Prospective Studies , Recurrence
13.
J Mol Cell Cardiol ; 85: 207-14, 2015 Aug.
Article in English | MEDLINE | ID: mdl-26073630

ABSTRACT

Genome-wide association studies (GWAS) have identified genetic variants in a number of chromosomal regions that are associated with atrial fibrillation (AF). The mechanisms underlying these associations are unknown, but are likely to involve effects of the risk haplotypes on expression of neighbouring genes. To investigate the association between genetic variants at AF-associated loci and expression of nearby candidate genes in human atrial tissue and peripheral blood. Right atrial appendage (RAA) samples were collected from 122 patients undergoing cardiac surgery, of these, 12 patients also had left atrial appendage samples taken. 22 patients had a history of AF. Peripheral blood samples were collected from 405 patients undergoing diagnostic cardiac catheterisation. In order to tag genetic variation at each of nine loci, a total of 367 single nucleotide polymorphisms (SNPs) were genotyped using the Sequenom platform. Total expression of 16 candidate genes in the nine AF-associated regions was measured by quantitative PCR. The relative expression of each allele of the candidate genes was measured on the Sequenom platform using one or more transcribed SNPs to distinguish between alleles in heterozygotes. We tested association between the SNPs of interest and gene expression using total gene expression (integrating cis and trans acting sources of variation), and allelic expression ratios (specific for cis acting influences), in atrial tissue and peripheral blood. We adjusted for multiple comparisons using a Bonferroni approach. In subsidiary analyses, we compared the expression of candidate genes between patients with and without a history of AF. Total expression of 15 transcripts of 14 genes and allelic expression ratio of 14 transcripts of 14 genes in genomic regions associated with AF were measured in right atrial appendage tissue. 8 of these transcripts were also expressed in peripheral blood. Risk alleles at AF-associated SNPs were associated in cis with an increased expression of PITX2a (2.01-fold, p=6.5×10(-4)); and with decreased expression of MYOZ1 (0.39 fold; p=5.5×10(-15)), CAV1 (0.89 fold; p=5.9×10(-8)), C9orf3 (0.91 fold; 1.5×10(-5)), and FANCC (0.94-fold; p=8.9×10(-8)) in right atrial appendage. Of these five genes, only CAV1 was expressed in peripheral blood; association between the same AF risk alleles and lower expression of CAV1 was confirmed (0.91 fold decrease; p=4.2×10(-5)). A history of AF was also associated with a decrease in expression of CAV1 in both right and left atria (0.84 and 0.85 fold, respectively; p=0.03), congruent with the magnitude of the effect of the risk SNP on expression, and independent of genotype. The analyses in peripheral blood showed association between AF risk SNPs and decreased expression of KCNN3 (0.85-fold; p=2.1×10(-4)); and increased expression of SYNE2 (1.12-fold; p=7.5×10(-24)); however, these associations were not detectable in atrial tissue. We identified novel cis-acting associations in atrial tissue between AF risk SNPs and increased expression of PITX2a/b; and decreased expression of CAV1 (an association also seen in peripheral blood), C9orf3 and FANCC. We also confirmed a previously described association between AF risk variants and MYOZ1 expression. Analyses of peripheral blood illustrated tissue-specificity of cardiac eQTLs and highlight the need for larger-scale genome-wide eQTL studies in cardiac tissue. Our results suggest novel aetiological roles for genes in four AF-associated genomic regions.


Subject(s)
Aminopeptidases/metabolism , Atrial Fibrillation/genetics , Carrier Proteins/metabolism , Caveolin 1/metabolism , Fanconi Anemia Complementation Group C Protein/metabolism , Homeodomain Proteins/metabolism , Muscle Proteins/metabolism , Transcription Factors/metabolism , Aminopeptidases/genetics , Atrial Fibrillation/metabolism , Carrier Proteins/genetics , Caveolin 1/genetics , Fanconi Anemia Complementation Group C Protein/genetics , Gene Expression , Gene Expression Regulation , Genetic Predisposition to Disease , Genome-Wide Association Study , Heart Atria/metabolism , Homeodomain Proteins/genetics , Humans , Muscle Proteins/genetics , Polymorphism, Single Nucleotide , Quantitative Trait Loci , Risk Factors , Transcription Factors/genetics , Homeobox Protein PITX2
14.
BMC Genet ; 15: 136, 2014 Dec 24.
Article in English | MEDLINE | ID: mdl-25539802

ABSTRACT

BACKGROUND: The ZFHX3 gene, located in Chromosome 16q22.3, codes for a transcription factor which is widely expressed in human tissues. Genome-wide studies have identified associations between variants within the gene and Kawasaki disease and atrial fibrillation. ZFHX3 has two main transcripts that utilise different transcription start sites. We examined the association between genetic variants in the 16q22.3 region and expression of ZFHX3 to identify variants that regulate gene expression. RESULTS: We genotyped 65 single-nucleotide polymorphisms to tag genetic variation at the ZFHX3 locus in two cohorts, 451 British individuals recruited in the North East of England and 310 mixed-ancestry individuals recruited in South Africa. Allelic expression analysis revealed that the minor (A) allele of rs8060701, a variant in the first intron of ZFHX3, was associated with a 1.16-fold decrease in allelic expression of both transcripts together, (p = 4.87e-06). The minor (C) allele of a transcribed variant, rs10852515, in the second exon of ZFHX3 isoform A was independently associated with a 1.36-fold decrease in allelic expression of ZFHX3 A (p = 7.06e-31), but not overall ZFHX3 expression. However, analysis of total gene expression of ZFHX3 failed to detect an association with genotype at any variant. Differences in linkage disequilibrium between the two populations allowed fine-mapping of the locus to a 7 kb region overlapping exon 2 of ZFHX3 A. We did not find any association between ZFHX3 expression and any of the variants identified by genome wide association studies. CONCLUSIONS: ZFHX3 transcription is regulated in a transcript-specific fashion by independent cis-acting transcribed polymorphisms. Our results demonstrate the power of allelic expression analysis and trans-ethnic fine mapping to identify transcript-specific cis-acting regulatory elements.


Subject(s)
Homeodomain Proteins/genetics , Transcription, Genetic , Adolescent , Adult , Aged , Aged, 80 and over , Atrial Fibrillation/genetics , Chromosomes, Human, Pair 16/genetics , Female , Gene Frequency , Genetic Predisposition to Disease , Genome-Wide Association Study , Homeodomain Proteins/metabolism , Humans , Linkage Disequilibrium , Male , Middle Aged , Mucocutaneous Lymph Node Syndrome/genetics , Phenotype , Polymorphism, Single Nucleotide , Quantitative Trait Loci , RNA, Messenger/genetics , RNA, Messenger/metabolism , Transcription Initiation Site , Young Adult
15.
Eur Heart J Case Rep ; 8(2): ytae038, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38313326

ABSTRACT

Background: Myocardial abnormalities are sometimes overlooked in congenital heart disease (CHD). The co-existence of hypertrophic cardiomyopathy is so uncommon that it is assumed to be a coincidence rather than an association. Case summary: A 24-year-old gentleman, who was previously clinically well following a staged Fontan palliation for single-ventricle CHD, was transferred to our centre following an out-of-hospital cardiac arrest. He had return of spontaneous circulation after a period of cardiopulmonary resuscitation. Initial electrocardiogram showed sinus bradycardia. Computed tomography pulmonary angiography ruled out pulmonary embolism. Transthoracic echocardiography and cardiac magnetic resonance (CMR) demonstrated marked ventricular hypertrophy with no left ventricular outflow tract obstruction. Punctate areas of late gadolinium enhancement were noted in the basal septum, and T1 values were consistent with fibrosis. Cardiac catheterization demonstrated low Fontan pressures and normal coronaries. Ventricular tachycardia rapidly degenerating into ventricular fibrillation was induced during electrophysiological studies. Genetic testing demonstrated a pathogenic cardiac myosin-binding protein C variant consistent with co-existent hypertrophic cardiomyopathy. Bisoprolol was initiated and a subcutaneous implantable cardiac defibrillator implanted 4 weeks after his initial presentation. Two years on, he remains well with no therapies from his defibrillator. As well as Fontan surveillance, cascade testing, exercise prescription, and pre-conception counselling were addressed during follow-up. Discussion: In CHD, ventricular hypertrophy may relate to congenital or acquired systemic outflow tract obstruction. Contemporary CMR techniques combined with genetic testing can be useful in differentiating between hypertrophy caused by congenital anomaly vs. concurrent cardiomyopathies. Multidisciplinary expertise is critical for accurate diagnosis and optimal care.

16.
Heart Rhythm ; 2024 Jun 06.
Article in English | MEDLINE | ID: mdl-38848856

ABSTRACT

BACKGROUND: Recurrent ventricular tachycardia (VT) can be treated by substrate modification of the myocardial scar by catheter ablation during sinus rhythm without VT induction. Better defining this arrhythmic substrate could help improve outcome and reduce ablation burden. OBJECTIVE: The study aimed to limit ablation within postinfarction scar to conduction channels within the scar to reduce VT recurrence. METHODS: Patients undergoing catheter ablation for recurrent implantable cardioverter-defibrillator therapy for postinfarction VT were recruited at 5 centers. Left ventricular maps were collected on CARTO using a Pentaray catheter. Ripple mapping was used to categorize infarct scar potentials (SPs) by timing. Earliest SPs were ablated sequentially until there was loss of the terminal SPs without their direct ablation. The primary outcome measure was sustained VT episodes as documented by device interrogations at 1 year, which was compared with VT episodes in the year before ablation. RESULTS: The study recruited 50 patients (mean left ventricular ejection fraction, 33% ± 9%), and 37 patients (74%) met the channel ablation end point with successful loss of latest SPs without direct ablation. There were 16 recurrences during 1-year follow-up. There was a 90% reduction in VT burden from 30.2 ± 53.9 to 3.1 ± 7.5 (P < .01) per patient, with a concomitant 88% reduction in appropriate shocks from 2.1 ± 2.7 to 0.2 ± 0.9 (P < .01). There were 8 deaths during follow-up. Those who met the channel ablation end point had no significant difference in mortality, recurrence, or VT burden but had a significantly lower ablation burden of 25.7 ± 4.2 minutes vs 39.9 ± 6.1 minutes (P = .001). CONCLUSION: Scar channel ablation is feasible by ripple mapping and can be an alternative to more extensive substrate modification techniques.

17.
Heart Rhythm ; 21(5): 571-580, 2024 May.
Article in English | MEDLINE | ID: mdl-38286246

ABSTRACT

BACKGROUND: Three-dimensional (3D) mapping of the ventricular conduction system is challenging. OBJECTIVE: The purpose of this study was to use ripple mapping to distinguish conduction system activation to that of adjacent myocardium in order to characterize the conduction system in the postinfarct left ventricle (LV). METHODS: High-density mapping (PentaRay, CARTO) was performed during normal rhythm in patients undergoing ventricular tachycardia ablation. Ripple maps were viewed from the end of the P wave to QRS onset in 1-ms increments. Clusters of >3 ripple bars were interrogated for the presence of Purkinje potentials, which were tagged on the 3D geometry. Repeating this process allowed conduction system delineation. RESULTS: Maps were reviewed in 24 patients (mean 3112 ± 613 points). There were 150.9 ± 24.5 Purkinje potentials per map, at the left posterior fascicle (LPF) in 22 patients (92%) and at the left anterior fascicle (LAF) in 15 patients (63%). The LAF was shorter (41.4 vs 68.8 mm; P = .0005) and activated for a shorter duration (40.6 vs 64.9 ms; P = .002) than the LPF. Fourteen of 24 patients had left bundle branch block (LBBB), with 11 of 14 (78%) having Purkinje potential-associated breakout. There were fewer breakouts from the conduction system during LBBB (1.8 vs 3.4; 1.6 ± 0.6; P = .039) and an inverse correlation between breakout sites and QRS duration (P = .0035). CONCLUSION: We applied ripple mapping to present a detailed electroanatomic characterization of the conduction system in the postinfarct LV. Patients with broader QRS had fewer LV breakout sites from the conduction system. However, there was 3D mapping evidence of LV breakout from an intact conduction system in the majority of patients with LBBB.


Subject(s)
Catheter Ablation , Heart Conduction System , Heart Ventricles , Myocardial Infarction , Tachycardia, Ventricular , Humans , Male , Female , Heart Conduction System/physiopathology , Middle Aged , Heart Ventricles/physiopathology , Heart Ventricles/diagnostic imaging , Tachycardia, Ventricular/physiopathology , Tachycardia, Ventricular/diagnosis , Tachycardia, Ventricular/etiology , Catheter Ablation/methods , Myocardial Infarction/physiopathology , Myocardial Infarction/complications , Electrocardiography , Purkinje Fibers/physiopathology , Aged , Imaging, Three-Dimensional , Body Surface Potential Mapping/methods
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