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Supplemental Digital Content is available in the text., Background: Brugada syndrome (BrS) is characterized by the type 1 Brugada ECG pattern. Pathogenic rare variants in SCN5A (mutations) are identified in 20% of BrS families in whom incomplete penetrance and genotype-negative phenotype-positive individuals are observed. E1784K-SCN5A is the most common SCN5A mutation identified. We determined the association of a BrS genetic risk score (BrS-GRS) and SCN5A mutation type on BrS phenotype in BrS families with SCN5A mutations. Methods: Subjects with a spontaneous type 1 pattern or positive/negative drug challenge from cohorts harboring SCN5A mutations were recruited from 16 centers (n=312). Single nucleotide polymorphisms previously associated with BrS at genome-wide significance were studied in both cohorts: rs11708996, rs10428132, and rs9388451. An additive linear genetic model for the BrS-GRS was assumed (6 single nucleotide polymorphism risk alleles). Results: In the total population (n=312), BrS-GRS ≥4 risk alleles yielded an odds ratio of 4.15 for BrS phenotype ([95% CI, 1.45–11.85]; P=0.0078). Among SCN5A-positive individuals (n=258), BrS-GRS ≥4 risk alleles yielded an odds ratio of 2.35 ([95% CI, 0.89–6.22]; P=0.0846). In SCN5A-negative relatives (n=54), BrS-GRS ≥4 alleles yielded an odds ratio of 22.29 ([95% CI, 1.84–269.30]; P=0.0146). Among E1784K-SCN5A positive family members (n=79), hosting ≥4 risk alleles gave an odds ratio=5.12 ([95% CI, 1.93–13.62]; P=0.0011). Conclusions: Common genetic variation is associated with variable expressivity of BrS phenotype in SCN5A families, explaining in part incomplete penetrance and genotype-negative phenotype-positive individuals. SCN5A mutation genotype and a BrS-GRS associate with BrS phenotype, but the strength of association varies according to presence of a SCN5A mutation and severity of loss of function.

Background Hypertrophic cardiomyopathy (HCM) remains the commonest cause of sudden cardiac death among young athletes. Differentiating between physiologically adaptive left ventricular (LV) hypertrophy observed in athletes' hearts and pathological HCM remains challenging. By quantifying the diffusion of water molecules, diffusion tensor imaging (DTI) MRI allows voxelwise characterization of myocardial microstructure. Purpose To explore microstructural differences between healthy volunteers, athletes, and HCM patients using DTI. Study Type Prospective cohort. Population Twenty healthy volunteers, 20 athletes, and 20 HCM patients. Field Strength/Sequence 3T/DTI spin echo. Assessment In‐house MatLab software was used to derive mean diffusivity (MD) and fractional anisotropy (FA) as markers of amplitude and anisotropy of the diffusion of water molecules, and secondary eigenvector angles (E2A)—reflecting the orientations of laminar sheetlets. Statistical Tests Independent samples t‐tests were used to detect statistical significance between any two cohorts. Analysis of variance was utilized for detecting the statistical difference between the three cohorts. Statistical tests were two‐tailed. A result was considered statistically significant at P ≤ 0.05. Results DTI markers were significantly different between HCM, athletes, and volunteers. HCM patients had significantly higher global MD and E2A, and significantly lower FA than athletes and volunteers. (MDHCM = 1.52 ± 0.06 × 10−3 mm2/s, MDAthletes = 1.49 ± 0.03 × 10−3 mm2/s, MDvolunteers = 1.47 ± 0.02 × 10−3 mm2/s, P

IntroductionElectrical coupling index (ECI) and contact force (CF) have been developed to aid lesion formation during catheter ablation. ECI measures tissue impedance and capacitance whilst CF measures direct contact. The aim was to determine whether the presence of catheter / tissue interaction information, such as ECI and CF, reduce time to achieve bidirectional cavotricuspid isthmus block during atrial flutter (AFL) ablation.MethodsPatients with paroxysmal or persistent AFL were randomised to CF visible (range 5-40g), CF not visible, ECI visible (change of 12%) or ECI not visible. Follow-up occurred at 3 and 6 months and included a 7 day ECG recording. The primary endpoint was time to bidirectional cavotricuspid isthmus block.Results114 patients were randomised, 16 were excluded. Time to bidirectional block was significantly shorter when ECI was visible (median 30.0 mins (IQR 31) to median 10.5mins (IQR 12) p 0.023) versus ECI not visible. There was a trend towards a shorter time to bidirectional block when CF was visible. Higher force was applied when CF was visible (median 9.03g (IQR 7.4) vs. 11.3g (5.5) p 0.017). There was no difference in the acute recurrence of conduction between groups. The complication rate was 2%, AFL recurrence was 1.1% and at 6 month follow-up, 12% had atrial fibrillation.ConclusionThe use of tissue contact information during AFL ablation was associated with reduced time taken to achieve bidirectional block when ECI was visible. Contact force data improved contact when visible with a trend towards a reduction in the procedural endpoint. ClinicalTrials.gov trial identifier: NCT02490033.

This report describes a patient presenting with a narrow complex tachycardia in the context of prior myocardial infarction and impaired ventricular function. Electrophysiological studies confirmed ventricular tachycardia and activation and entrainment mapping demonstrated a critical isthmus within an area of scar involving the His-Purkinje system accounting for the narrow QRS morphology. This very rare case shares some similarities with upper septal ventricular tachycardia seen in patients with structurally normal hearts, but to our knowledge has not been seen previously in patients with ischemic heart disease.

BACKGROUND: Catheter ablation is an effective treatment for symptomatic individuals with atrial fibrillation (AF) but is associated with a risk of periprocedual stroke. Recent data suggest that this risk may be abolished if catheter ablation is performed with uninterrupted warfarin (UW). We sought to compare the incidence, severity and timing of periprocedural stroke between 2 periprocedural anticoagulation protocols: bridging low-molecular-weight heparin (LMWH) and UW. METHODS AND RESULTS: Periprocedural stroke (≤14 days) was assessed in 2,855 ablations performed in 1,813 patients. Thromboembolic stroke occurred in 11/1,653 (0.7%) procedures with bridging LMWH and in 5/1,202 (0.4%) procedures on UW (P = 0.5). Four of the 5 strokes (80%) on UW occurred despite a therapeutic INR and a mean activated clotting time of ≥300 seconds and 4/5 strokes (80%) occurred in patients with a CHADS2 score of 0. Eleven of 16 (69%) strokes overall occurred within 24 hours of the procedure. All 4 strokes resulting in major neurological deficit occurred in the LMWH group. Major bleeding complications occurred in 6.0% of patients in the bridging LMWH group compared to 4.0% in the UW group (P = 0.02). CONCLUSIONS: In contrast to existing data, periprocedural stroke still occurs despite therapeutic anticoagulation throughout the operative period. The optimal strategy to protect patients against thromboembolic stroke remains unclear.

A 29-year-old male was referred in 1985 for further arrhythmia management after repeated cardioversion for broad complex tachycardia that was unresponsive to numerous antiarrhythmic agents. The cause of his arrhythmia was considered a complication of viral myocarditis. His baseline ECG and echocardiogram were normal. Two different clinical tachycardias were documented during his admission, both with left bundle morphology and inferior axis, but varying cycle length (370 ms and 240 ms) and patterns of transition in the precordial leads. Invasive electrophysiological assessment demonstrated ventricular tachycardia (VT) originating in the right ventricular outflow tract and because of the risks of direct current ablation, surgical intervention was advised. At surgery, on visual inspection the right ventricular outflow tract was yellowish-grey in color and poorly contractile, and a 7×4cm section was removed, histological examination of which showed increased fibrosis. He remained well for many years controlled on dofetilide, but in 2009 he experienced a further episode of VT (Figure 1A) and after cardioversion his 12-lead ECG showed T-wave inversion to V5 with epsilon waves in leads V1 through V3. On cardiac MRI the right ventricle was dilated (115 mls/m2) with reduced function (ejection fraction 34%) but no aneurysms or free wall dyskinesia. On review of previous ECGs (Figure 2) there were no abnormalities of either …

Background— Restoring sinus rhythm in patients with heart failure (HF) and atrial fibrillation (AF) may improve left ventricular (LV) function and HF symptoms. We sought to compare the effect of a catheter ablation strategy with that of a medical rate control strategy in patients with persistent AF and HF. Methods and Results— Patients with persistent AF, symptomatic HF, and LV ejection fraction P =0.015). Ablation was associated with better peak oxygen consumption (22±6 versus 18±6 mL/kg per minute; P =0.014) and Minnesota living with HF questionnaire score (24±22 versus 47±22; P =0.001) compared with rate control. Conclusions— Catheter ablation is effective in restoring sinus rhythm in selected patients with persistent AF and HF, and can improve LV function, functional capacity, and HF symptoms compared with rate control. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT01411371

Aims: Measurement of circulating biomarkers of fibrosis may have a role in selecting patients and treatment strategy for catheter ablation. Pro-collagen type III N-terminal pro-peptide (PIIINP), C-telopeptide of type I collagen (ICTP), fibroblast growth factor 23 (FGF-23), and galectin 3 (gal-3) have all been suggested as possible biomarkers for this indication, but studies assessing whether peripheral levels reflect intra-cardiac levels are scarce.Methods and results: We studied 93 patients undergoing ablation for paroxysmal atrial fibrillation (AF) (n = 63) or non-paroxysmal AF (n = 30). Femoral venous, left and right atrial, and coronary sinus blood were analysed using ELISA to determine biomarker levels. Levels were compared with control patients (n = 36) and baseline characteristics, including left atrial voltage mapping data. C-telopeptide of type I collagen levels were higher in AF than in non-AF patients (P = 0.007). Peripheral ICTP levels were higher than all intra-cardiac levels (P Conclusions: Atrial fibrillation patients have higher levels of circulating ICTP than matched non-AF controls. In AF ablation patients, intra-cardiac sampling of FGF-23 or PIIINP gives no further information over peripheral sampling. For gal-3 and ICTP, intra-cardiac sampling may be necessary to assess their association with intra-cardiac processes. None of the biomarkers is related to fibrosis assessed by left atrial voltage.

Athletes who train regularly can develop left ventricular (LV) hypertrophy, which can be difficult to differentiate from hypertrophic cardiomyopathy (HCM), the leading cause of sudden cardiac death in young athletes. Current guidelines advise that patients with HCM should avoid competitive sport

The early repolarization (ER) pattern on the 12-lead electrocardiogram is characterized by J point elevation in the inferior and/or lateral leads. The ER pattern is associated with an increased risk of ventricular arrhythmias and sudden cardiac death (SCD). Based on studies in animal models and genetic studies, it has been proposed that J point elevation in ER is a manifestation of augmented dispersion of repolarization which creates a substrate for ventricular arrhythmia. A competing theory regarding early repolarization syndrome (ERS) proposes that the syndrome arises as a consequence of abnormal depolarization. In recent years, multiple clinical studies have described the characteristics of ER patients with VF in more detail. The majority of these studies have provided evidence to support basic science observations. However, not all clinical observations correlate with basic science findings. This review will provide an overview of basic science and genetic research in ER and correlate basic science evidence with the clinical phenotype.

Aims In patients undergoing epicardial catheter ablation of ventricular tachycardia (VT), current guidelines recommend obtaining pericardial access prior to heparinization to minimize bleeding complications. Consequently, access is obtained before endocardial mapping (leading to unnecessary punctures) or during an additional procedure. We present our experience of obtaining pericardial access during the index procedure in heparinized patients. Methods and results Patients undergoing catheter ablation of VT in whom pericardial access was performed after heparinization were included. Clinical and procedural data and complications were recorded. Electrocardiograms (ECGs) were analysed for published criteria suggesting an epicardial ablation target and compared with patients (matched for substrate) undergoing successful endocardial ablation. Seventeen patients (13 males, age 58 ± 16 years, 8 (47%) ischaemic) were evaluated. Pericardial access was achieved in 16 (94%), including 2 patients with prior epicardial ablation. The mean activated clotting time was 273 ± 36 s. No bleeding complications occurred. In three patients, inadvertent puncture of the right ventricle caused no adverse consequences. An epicardial ablation target was found in nine of which three (33%) had ECG criteria, suggesting an epicardial circuit. In comparison 5 of 17 patients undergoing successful endocardial ablation had at least one ECG criterion suggesting an epicardial ablation target. Conclusion Obtaining pericardial access for epicardial catheter ablation for VT appears to be safe in heparinized patients. Electrocardiogram criteria suggesting an epicardial ablation target lack the sensitivity and specificity accurately to predict which patients might need epicardial ablation. Performing pericardial access in heparinized patients therefore may reduce unnecessary punctures and reduce the number of additional procedures in some patients.

Background: Robotic catheter ablation aims to improve outcomes after ablation of atrial fibrillation (AF) through improved lesion quality. This study examined electrogram attenuation as a measure of efficacy in response to robotic (ROB) and manual (MAN) ablation. Methods: Patientswith paroxysmal AF undergoing ablation as part of an ongoing randomized controlled trial were studied (Clinical Trials Registration NCT01037296). Patients underwent pulmonary vein isolation using NavX (St. Jude Medical, St. Paul, MN, USA). Patients were randomized to MAN or ROB catheter ablation using a 3.5-mm irrigated-tip catheter with standardized ablation settings. Bipolar electrogram voltage was measured at 0, 5, 10, 20, and 30 seconds after ablation onset. Distance from ablation lesion to the left atrial surface on NavX were calculated. Results: Similar ablation energy was delivered in ROB and MAN groups, achieving comparable rates of PV isolation (100% vs 98%). The bipolar voltages of 4,434 electrograms from 303 ablation lesions (146 ROB, 157 MAN) were measured. At 30 seconds, signal attenuation was greater in the ROB group than MAN (mean 65 ± 4% vs 55 ± 4% of baseline voltage, P < 0.01). A total of 2,064 NavX ablation lesions were assessed (906 ROB and 1,158 MAN). ROB lesions were on average 0.52 mm further inside the geometry than MAN (P < 0.0001). Conclusions: Robotic ablation results in greater signal attenuation in man. This is achieved despite manual lesions being closer to the left atrial surface. Catheter stability and constant energy delivery may be key to achieving signal attenuation, rather than increased contact force. ©2012, The Authors. Journal compilation ©2012 Wiley Periodicals, Inc.

Aims To investigate the impact of variant pulmonary vein (PV) anatomy and the use of three-dimensional image integration (3D-II) on long-term efficacy of catheter ablation for atrial fibrillation (AF). Methods Consecutive procedures from 2002 to 2007 were analysed from a prospective database. All patients underwent wide area circumferential ablation, with linear lesions added and complex fractionated electrograms targeted for persistent AF. Imaging was segmented on Carto to assess PV anatomy. Results Three hundred and fifty patients underwent 1.9 ± 0.9 procedures. The mean age was 57 ± 11 years, 73% males, and 55% paroxysmal AF. Freedom from AF/atrial tachycardia was 42% for paroxysmal AF and 20% for persistent AF at 3.1 years after the first procedure, or 86 and 66%, respectively, at 2.5 years after the last procedure. The Kaplan–Meier analysis showed a trend towards improved single-procedure efficacy with 3D-II (8.9% difference, P = 0.087) and a reduction in the number of procedures per patient from 2.1 ± 1.1 to 1.8 ± 0.9 ( P < 0.0001). The use of 3D-II improved single-procedure efficacy with Carto (13.3% difference, P = 0.018), but not with Ensite NavX. Variant PV anatomy was identified in 28% and was associated with a lower single-procedure efficacy (10.0% difference, P = 0.024) but with no effect on final outcome. Multivariate analysis confirmed the impact of 3D-II [hazard ratio (HR) for recurrence of AF 0.67, P = 0.020] and variant PV anatomy (HR 1.37, P = 0.044). Conclusion The use of 3D-II improves single-procedure efficacy of PV isolation for AF. Variant PV anatomy was associated with a lower single-procedure success rate.

Novel technologies have been developed recently to assess contact between the ablation catheter and the underlying tissue in an attempt to improve safe and effective lesion delivery. The most recently developed technology is the SmartTouch™ catheter which is an open irrigated-tip catheter integrated within the CARTO 3 3D mapping system. In this review we consider the role of contact force technology, evaluate the published data and discuss the potential applications of this novel technology.

Atrial and ventricular tachyarrhythmia are often sustained by re-entrant propagation, and explained by deterministic models. A quantitative, stochastic description of self-termination provides an alternative to the current paradigm for re-entrant tachyarrhythmia - that of triggers and a substrate, modelled by parametrically heterogeneous deterministic partial differential equations Atrial and ventricular data was from recordings obtained during routine clinical monitoring and treatment, either noninvasively or invasively. Atrial and ventricular tachycardia are characterised by their initiation times and durations, re-presented as instantaneous rates, whose means estimate transition probabilities/s for onset and termination. These estimated probabilities range from 10−9 to 10−1/s.

Catheter ablation is an effective treatment for symptomatic individuals with atrial fibrillation (AF) but is associated with a risk of periprocedual stroke. Recent data suggest that this risk may be abolished if catheter ablation is performed with uninterrupted warfarin (UW). We sought to compare the incidence, severity and timing of periprocedural stroke between 2 periprocedural anticoagulation protocols: bridging low-molecular-weight heparin (LMWH) and UW.Periprocedural stroke (≤14 days) was assessed in 2,855 ablations performed in 1,813 patients. Thromboembolic stroke occurred in 11/1,653 (0.7%) procedures with bridging LMWH and in 5/1,202 (0.4%) procedures on UW (P = 0.5). Four of the 5 strokes (80%) on UW occurred despite a therapeutic INR and a mean activated clotting time of ≥300 seconds and 4/5 strokes (80%) occurred in patients with a CHADS2 score of 0. Eleven of 16 (69%) strokes overall occurred within 24 hours of the procedure. All 4 strokes resulting in major neurological deficit occurred in the LMWH group. Major bleeding complications occurred in 6.0% of patients in the bridging LMWH group compared to 4.0% in the UW group (P = 0.02).In contrast to existing data, periprocedural stroke still occurs despite therapeutic anticoagulation throughout the operative period. The optimal strategy to protect patients against thromboembolic stroke remains unclear.

Robotic catheter ablation aims to improve outcomes after ablation of atrial fibrillation (AF) through improved lesion quality. This study examined electrogram attenuation as a measure of efficacy in response to robotic (ROB) and manual (MAN) ablation.Patients with paroxysmal AF undergoing ablation as part of an ongoing randomized controlled trial were studied (Clinical Trials Registration NCT01037296). Patients underwent pulmonary vein isolation using NavX (St. Jude Medical, St. Paul, MN, USA). Patients were randomized to MAN or ROB catheter ablation using a 3.5-mm irrigated-tip catheter with standardized ablation settings. Bipolar electrogram voltage was measured at 0, 5, 10, 20, and 30 seconds after ablation onset. Distance from ablation lesion to the left atrial surface on NavX were calculated.Similar ablation energy was delivered in ROB and MAN groups, achieving comparable rates of PV isolation (100% vs 98%). The bipolar voltages of 4,434 electrograms from 303 ablation lesions (146 ROB, 157 MAN) were measured. At 30 seconds, signal attenuation was greater in the ROB group than MAN (mean 65 ± 4% vs 55 ± 4% of baseline voltage, P0.01). A total of 2,064 NavX ablation lesions were assessed (906 ROB and 1,158 MAN). ROB lesions were on average 0.52 mm further inside the geometry than MAN (P0.0001).Robotic ablation results in greater signal attenuation in man. This is achieved despite manual lesions being closer to the left atrial surface. Catheter stability and constant energy delivery may be key to achieving signal attenuation, rather than increased contact force.

Background— Small selected cohort studies suggest that mutations in the cardiac myosin binding protein-C (MYBPC3) gene cause late-onset, clinically benign hypertrophic cardiomyopathy (HCM). The aim of this study was to test this hypothesis in a large series of families with HCM associated with MYBPC3 mutations. Methods and Results— The initial study population comprised 57 probands with 42 mutations (26 [61.9%] novel) in MYBPC3. Missense mutations (15, 45.6%) were the most frequent, and multiple mutations occurred in 4 (7.0%) probands. Another 110 mutation carriers were identified during familial evaluation; 38 were clinically affected with left ventricular hypertrophy ≥13 mm. Disease penetrance was, therefore, incomplete (56.9% in all mutation carriers, 34.5% in relatives), related to age (38.4% P P =0.03). In 9 families (25 individuals) with the R502W mutation, there was marked heterogeneity in age at diagnosis (5 to 80 years), pattern of hypertrophy (11 none, 9 asymmetrical, 3 concentric, 1 apical, 1 eccentric), and prognosis (premature sudden death in 2 individuals compared with survival to advanced age in 6 individuals). During follow up of 7.9+/−4.5 years, in 82 clinically affected individuals the annual risk of sudden death and all cause mortality was 0.46% and 0.93% per year, respectively. Conclusions— Disease expression in families with HCM related to MYBPC3 mutations shows marked heterogeneity with incomplete, age-related, and gender specific penetrance. Importantly, complex genetic status is observed and should be considered when mutation analysis and cascade screening is used in the evaluation of at risk family members.

Hypertrophic cardiomyopathy (HCM) is caused by mutations in genes encoding sarcomere proteins. Mutations inMYL3, encoding the essential light chain of myosin, are rare and have been associated with sudden death. Both recessive and dominant patterns of inheritance have been suggested. We studied a large family with a 38-year-old asymptomatic HCM-affected male referred because of a murmur. The patient had HCM with left ventricular hypertrophy (max WT 21 mm), a resting left ventricular outflow gradient of 36 mm Hg, and left atrial dilation (54 mm). Genotyping revealed heterozygosity for a novel missense mutation, p.V79I, inMYL3. The mutation was not found in 300 controls, and the patient had no mutations in 10 sarcomere genes. Cascade screening revealed a further nine heterozygote mutation carriers, three of whom had ECG and/or echocardiographic abnormalities but did not fulfil diagnostic criteria for HCM. The penetrance, if we consider this borderline HCM the phenotype of the p.V79I mutation, was 40%, but the mean age of the nonpenetrant mutation carriers is 15, while the mean age of the penetrant mutation carriers is 47. The mutation affects a conserved valine replacing it with a larger isoleucine residue in the region of contact between the light chain and the myosin lever arm. In conclusion,MYL3mutations can present with low expressivity and late onset.

To investigate whether catheter ablation of atrial fibrillation (AF) reduces stroke rate or mortality.An international multicentre registry was compiled from seven centres in the U.K. and Australia for consecutive patients undergoing catheter ablation of AF. Long-term outcomes were compared with (1) a cohort with AF treated medically in the Euro Heart Survey, and (2) a hypothetical cohort without AF, age and gender matched to the general population. Analysis of stroke and death was carried out after the first procedure (including peri-procedural events) regardless of success, on an intention-to-treat basis.1273 patients, aged 58±11 years, 56% paroxysmal AF, CHADS(2) score 0.7±0.9, underwent 1.8±0.9 procedures. Major complications occurred in 5.4% of procedures, including stroke/TIA in 0.7%. Freedom from AF following the last procedure was 85% (76% off antiarrhythmic drugs) for paroxysmal AF, and 72% (60% off antiarrhythmic drugs) for persistent AF. During 3.1 (1.0-9.6) years from the first procedure, freedom from AF predicted stroke-free survival on multivariate analysis (HR=0.30, CI 0.16 to 0.55, p0.001). Rates of stroke and death were significantly lower in this cohort (both 0.5% per patient-year) compared with those treated medically in the Euro Heart Survey (2.8% and 5.3%, respectively; p0.0001). Rates of stroke and death were no different from those of the general population (0.4% and 1.0%, respectively).Restoration of sinus rhythm by catheter ablation of AF is associated with lower rates of stroke and death compared with patients treated medically.

AF Ablation on Uninterrupted Warfarin. Introduction: Catheter ablation for atrial fibrillation is an effective treatment for symptomatic patients who have failed drug therapy. Recent studies using intracardiac echocardiography have demonstrated that ablation can be performed safely on uninterrupted warfarin and may be superior to bridging low molecular weight heparin (LMWH). We sought to assess the safety of an uninterrupted warfarin protocol using a simplified ablation protocol in a prospective controlled study. Methods: Two anticoagulation regimes for patients undergoing catheter ablation for atrial fibrillation were evaluated—a bridging LMWH group and an uninterrupted warfarin group. Bleeding complications were compared between the 2 groups. Results: In total 198 patients were evaluated (109 bridging LMWH, 89 uninterrupted warfarin). The preprocedure INR in the LMWH group (mean age 60.6 years, 72% male) was 1.2 ± 0.3 compared to 2.3 ± 0.5 in the uninterrupted warfarin group (mean age 60.9 years, 69% male). The primary outcome (a composite of major and minor bleeding complications) was observed in 78% in the LMWH group compared to 56% in the warfarin group (P = 0.001), mainly due to increased pain at the venous access site (41% vs 16%, P = 0.001). Two patients undergoing ablation on warfarin required pericardiocentesis for cardiac tamponade. Drug costs were lower in the warfarin group ($64.77 ± 31.86 vs $20.76 ± 15.60, P = 0.005), but the overall cost of treatment per patient (including bed occupancy costs) was similar in the LMWH group compared to the warfarin group ($883.96 ± 278.78 vs $816.59 ± 182.72, P = 0.06). Conclusion: Catheter ablation for atrial fibrillation can be performed safely on uninterrupted warfarin without intracardiac echocardiography, with a reduced risk of bleeding complications. (J Cardiovasc Electrophysiol, Vol. 22, pp. 265-270, March 2011)

Hypertrophic cardiomyopathy is primarily caused by mutations in genes encoding cardiac sarcomere proteins. Large screening studies identify mutations in 35-65% of the diagnosed patients and 15-30% of these are discovered within the MYBPC3 gene encoding the cardiac myosin binding protein C. The aim of this study is to determine whether intronic variation flanking the three micro-exons in MYBPC3 is disease-causing. Two hundred and fifty unrelated patients with hypertrophic cardiomyopathy were genotyped in MYBPC3, using automated single-strand conformation polymorphism, and sequenced for confirmation. Mutations located in the flanking introns of the MYBPC3 micro-exons were examined using in silico methods. Ectopic expression of mRNA in blood leukocytes in the respective patients was examined using reverse transcription-PCR. A total of seven mutations were discovered in the introns flanking the two micro-exons 10 and 14, but none were found in introns flanking exon 11. Functional studies together with co-segregation analysis indicate that four mutations are associated with HCM, in the respective patients. All four mutations result in premature termination codons, which suggests that haploinsufficiency is a pathogenic mechanism of this type of mutation. It is demonstrated that the use of in silico methods together with RNA studies on peripheral blood leukocytes is a useful tool to evaluate the potential effects of mutations on pre-mRNA splicing.

T1 mapping by cardiovascular magnetic resonance is a rapidly evolving method for the quantitative assessment of tissue characteristics in cardiac disease. The myocardial T1 time can be measured without contrast (native T1) or following the administration of intravenous gadolinium-based contrast agent (post-contrast T1). By combining both of these measures, the myocardial extracellular volume fraction can be approximated. This value has been validated histologically in various inherited cardiomyopathies. Due to overlapping phenotypes, the diagnosis of inherited cardiomyopathy can at times be challenging. In this article we discuss when T1 mapping may be a useful tool in the differential diagnosis of cardiomyopathy. We also present evidence of when T1 mapping provides incremental risk stratification over other biomarkers.

Introduction Idiopathic VF (IVF) maybe over diagnosed depending on which definition is used. The aim of this study was to investigate the incidence of IVF and the frequency with which patients are inappropriately labelled with IVF in a tertiary centre with a specialist inherited arrhythmia clinic. Methods Medical notes were retrospectively reviewed on all patients who had an ICD inserted between June 1994 and May 2012. All patients who had undergone a secondary prevention ICD for either ‘unknown’ or ‘idiopathic’ reasons selected. The electronic records and medical notes were reviewed to reveal whether in light of further testing a different diagnosis was given. IVF was defined as VF with no identifiable cause after full clinical investigation which included ECG, signal-averaged ECG, echo, exercise test (if physically able), ajmaline test, coronary angiogram and cardiac MRI. Results Of 2189 patients, 135 had a working diagnosis of IVF. Of these seven had limited clinical data and were excluded. Of the remaining 128 patients (98 M), only 28 (22%) had a confirmed diagnosis of IVF. 15 patients (12%) required further testing before all causes could be excluded resulting in a diagnosis of IVF (9 need an exercise test and 12 need an ajmaline test). The remaining 85 patients were found to have DCM or IHD 72 (56%), HCM 3 (2%), ARVC 4 (3%), LQTS 2 (1.5%), Brugada 2 (1.5%), 1 with cardiac sarcoidosis and 1 with Wolff Parkinson White syndrome. Of the 28 patients with confirmed IVF (mean age 43±13) and follow up ranging from 2–216 months, 16 (57%) had evidence of early repolarization (ER) on their ECG (J point notching/slurring in ≥2 leads). 8/28 (28%) IVF patients had at least 1 appropriate therapy during follow up and 1 patient required catheter ablation for recurrent VF. Conclusions IVF may be diagnosed prematurely which can result in a failure to screen family for inherited causes of VF. Appropriate therapy is common in these patients and there is a high prevalence of ER but because of its frequency in the general population this is not a useful screening marker.

A 53 year old Vietnamese man developed chest pain at rest and dialled the emergency services. The ambulance service identified ST elevation on 12 lead electrocardiography (ECG) and according to local protocol brought him direct to our cardiac centre with a suspected ST elevation myocardial infarction. On arrival he reported a three hour history of central chest pain without radiation or associated symptoms. He was a current smoker but had no other risk factors for coronary artery disease. Examination was unremarkable and an ECG was performed on arrival. In lead V1 there was 2 mm of coved J point elevation, with an inverted T wave. In V2 there was 4 mm of J point elevation, with a saddle shaped ST segment and an upright T wave. In V3 the J point, ST segment, and T wave were within normal limits. He underwent immediate coronary angiography, which showed mild atheroma in the left anterior descending artery, but no obstructive lesions, and transthoracic echocardiography showed normal cardiac structure with good biventricular function. Overnight he developed a productive cough associated with a fever. Serial ECGs were recorded while he was febrile and showed 3 mm of coved J point elevation in lead V1 and 5 mm of coved J point elevation in V2, with associated T wave inversion. On further questioning he admitted to a history of well tolerated intermittent palpitations of up to an hour’s duration. His father had died suddenly and unexpectedly by falling from a bridge, but …

Introduction Reports of the prevalence of left atrial appendage (LAA) thrombus among patients undergoing catheter ablation for atrial fibrillation (AF) vary and may depend on the anticoagulation regime used prior to the procedure. Methods We undertook transoesophageal echocardiograms (TOE) in 586 patients (age 59.9±0.4 years old, mean±SE, 64.5% male) undergoing catheter ablation for AF who were anti-coagulated on warfarin (international normalised ratio 2–3) for at least 3 consecutive weeks prior to procedure and maintained on warfarin for the procedure itself. Results LAA thrombus was identified in 3 patients from 586 (0.5%) despite all 3 having therapeutic INRs (2.2, 2.2 and 3.3 respectively). None of the remaining patients had a peri-procedural stroke. The three patients with LAA thrombus had CHADS 2 scores of ≥1 and CHA2DS2-VASc scores of ≥2. All three patients had impaired left ventricular systolic function (LVSF), and LAA emptying velocities of 2 (0.9±0.1 vs 0.7±0.001) and CHA2DS2-VASc scores (1.7±0.1 vs 1.4±0.1), and larger LA diameter (4.95±0.09 vs 4.38±0.05 cm, OR for LA >4.6 cm: 2.4, 95% CI 2.13 to 5.41), and were more likely to have impaired LVSF (OR: 2.66, 95% CI 1.52 to 4.66) compared to those with higher velocities on multivariate analysis. Conclusions The prevalence of LAA thrombus using our anticoagulation regime is extremely low. Providing patients have been therapeutically anti-coagulated, pre-operative TOE need only be performed in patients with a CHADS 2 score of ≥1/CHA2DS2-VASc score of ≥2 or when LA diameter is >4.6 cm. This criteria has the highest sensitivity (84%) for identifying LAA velocities of

Background Regional contractile dysfunction is a frequent finding in hypertrophic cardiomyopathy (HCM). We aimed to investigate the contribution of different tissue characteristics in HCM to regional contractile dysfunction. Methods We prospectively recruited 50 patients with HCM who underwent cardiovascular magnetic resonance (CMR) studies at 3.0 T including cine imaging, T1 mapping and late gadolinium enhancement (LGE) imaging. For each segment of the American Heart Association model segment thickness, native T1, extracellular volume (ECV), presence of LGE and regional strain (by feature tracking and tissue tagging) were assessed. The relationship of segmental function, hypertrophy and tissue characteristics were determined using a mixed effects model, with random intercept for each patient. Results Individually segment thickness, native T1, ECV and the presence of LGE all had significant associations with regional strain. The first multivariable model (segment thickness, LGE and ECV) demonstrated that all strain parameters were associated with segment thickness (P