Critically ill patients with infective endocarditis, neurological complications and indication for cardiac surgery: a multicenter propensity-adjusted study.

BACKGROUND: The benefit-risk balance and optimal timing of surgery for severe infective endocarditis (IE) with ischemic or hemorrhagic strokes is unknown. The study aim was to compare the neurological outcome between patients receiving surgery or not. METHODS: In a prospective register-based multicenter ICU study, patients were included if they met the following criteria: (i) left-sided IE with an indication for heart surgery; (ii) with cerebral complications documented by cerebral imaging before cardiac surgery; (iii) with Sequential Organ Failure Assessment score ≥ 3. Exclusion criteria were isolated right-sided IE, in-hospital acquired IE and patients with cerebral complications only after cardiac surgery. In the primary analysis, the prognostic value of surgery in term of disability at 6 month was assessed by using a propensity score-adjusted logistic regression. RESULTS: 192 patients were included including ischemic stroke (74.5%) and hemorrhagic lesion (15.6%): 67 (35%) had medical treatment and 125 (65%) cardiac surgery. In the propensity score-adjusted logistic regression, a favorable 6-month neurological outcome was associated with surgery (odds ratio 13.8 (95% CI 6.2-33.7). The 1-year mortality was strongly reduced with surgery in the fixed-effect propensity-adjusted Cox model (hazard ratio 0.18; 95% CI 0.11-0.27; p < 0.001). These effects remained whether the patients received delayed surgery (n = 62/125) or not and whether they were deeply comatose (Glasgow Coma Scale ≤ 10) or not. CONCLUSIONS: In critically ill IE patients with an indication for surgery and previous cerebral events, a better propensity-adjusted neurological outcome was associated with surgery compared with medical treatment.

In vitro characterization of rare anti-αIIbß3 isoantibodies produced by patients with Glanzmann thrombasthenia that severely block fibrinogen binding and generate procoagulant platelets via complement activation.

Background: Glanzmann thrombasthenia (GT) is a rare bleeding disorder caused by inherited defects of the platelet αIIbß3 integrin. Platelet transfusions can be followed by an immune response that can block integrin function by interfering with fibrinogen binding. Objectives: In this study, we aimed to determine the prevalence of such isoantibodies and better characterize their pathogenic properties. Methods: Twelve patients with GT were evaluated for anti-αIIbß3 isoantibodies. Sera from patients with GT with or without anti-αIIbß3 isoantibodies were then used to study their in vitro effect on platelets from healthy donors. We used several approaches (IgG purification, immunofluorescence staining, and inhibition of signaling pathways) to characterize the pathogenic properties of the anti-αIIbß3 isoantibodies. Results: Only 2 samples were able to severely block integrin function. We observed that these 2 sera caused a reduction in platelet size similar to that observed when platelets become procoagulant. Mixing healthy donor platelets with patients' sera or purified IgGs led to microvesiculation, phosphatidylserine exposure, and induction of calcium influx. This was associated with an increase in procoagulant platelets. Pore formation and calcium entry were associated with complement activation, leading to the constitution of a membrane attack complex (MAC) with enhanced complement protein C5b-9 formation. This process was inhibited by the complement 5 inhibitor eculizumab and reduced by polyvalent human immunoglobulins. Conclusion: Our data suggest that complement activation induced by rare blocking anti-αIIbß3 isoantibodies may lead to the formation of a MAC with subsequent pore formation, resulting in calcium influx and procoagulant platelet phenotype.

A single F153Sß3 mutation causes constitutive integrin αIIbß3 activation in a variant form of Glanzmann thrombasthenia.

This report identifies a novel variant form of the inherited bleeding disorder Glanzmann thrombasthenia, exhibiting only mild bleeding in a physically active individual. The platelets cannot aggregate ex vivo with physiologic agonists of activation, although microfluidic analysis with whole blood displays moderate ex vivo platelet adhesion and aggregation consistent with mild bleeding. Immunocytometry shows reduced expression of αIIbß3 on quiescent platelets that spontaneously bind/store fibrinogen, and activation-dependent antibodies (ligand-induced binding site-319.4 and PAC-1) report ß3 extension suggesting an intrinsic activation phenotype. Genetic analysis reveals a single F153Sß3 substitution within the ßI-domain from a heterozygous T556C nucleotide substitution of ITGB3 exon 4 in conjunction with a previously reported IVS5(+1)G>A splice site mutation with undetectable platelet messenger RNA accounting for hemizygous expression of S153ß3. F153 is completely conserved among ß3 of several species and all human ß-integrin subunits suggesting that it may play a vital role in integrin structure/function. Mutagenesis of αIIb-F153Sß3 also displays reduced levels of a constitutively activated αIIb-S153ß3 on HEK293T cells. The overall structural analysis suggests that a bulky aromatic, nonpolar amino acid (F,W)153ß3 is critical for maintaining the resting conformation of α2- and α1-helices of the ßI-domain because small amino acid substitutions (S,A) facilitate an unhindered inward movement of the α2- and α1-helices of the ßI-domain toward the constitutively active αIIbß3 conformation, while a bulky aromatic, polar amino acid (Y) hinders such movements and restrains αIIbß3 activation. The data collectively demonstrate that disruption of F153ß3 can significantly alter normal integrin/platelet function, although reduced expression of αIIb-S153ß3 may be compensated by a hyperactive conformation that promotes viable hemostasis.

Brain imaging determinants of functional prognosis after severe endocarditis: a multicenter observational study.

OBJECTIVE: We developed a detailed imaging phenotype of the cerebral complications in critically ill patients with infective endocarditis (IE) and determine whether any specific imaging pattern could impact prognostic information. METHODS: One hundred ninety-two patients admitted to the intensive care units of seven tertiary centers with severe, definite left IE and neurological complications were included. All underwent cerebral imaging few days after admission to define the types of lesions, their volumes, and their locations using voxel-based lesion-symptom mapping (VLSM). We employed uni- and multi-variate logistic regression analyses to explore the associations among imaging features and other prognostic variables and the 6-month modified Rankin Scale (mRS) score. RESULTS: Ischemic lesions were the most common lesions (75%; mean volume, 15.3 ± 33 mL) followed by microbleeds (50%; mean number, 4 ± 7.5), subarachnoidal hemorrhages (20%), hemorrhagic strokes (16%; mean volume, 14.6 ± 21 mL), and hemorrhagic transformations (10%; mean volume, 5.6 ± 11 mL). The volume of hemorrhagic transformations, the severity of leukopathy, and the compromises of certain locations on the motor pathway from the VLSM were associated with a poor 6-month mRS score on univariate analyses. However, upon multivariate analyses, no such specific imaging pattern independently predicted the mRS; this was instead influenced principally by age (OR = 1.03 [1.004-1.06]) and cardiac surgery status (OR = 0.06 [0.02-0.16]) in the entire cohort, and by age (OR = 1.04 [1.01-1.08]) and Staphylococcus aureus status (OR = 2.86 [1.19-6.89]) in operated patients. CONCLUSIONS: In a cohort of severely ill IE patients with neurological complications, no specific imaging pattern could be highlighted as a reliable predictor of prognosis.

Effect of electrode size and spacing on electrograms: Optimized electrode configuration for near-field electrogram characterization.

BACKGROUND: Detailed effects of electrode size on electrograms (EGMs) have not been systematically examined. OBJECTIVES: We aimed to elucidate the effect of electrode size on EGMs and investigate an optimal configuration of electrode size and interelectrode spacing for gap detection and far-field reduction. METHODS: This study included 8 sheep in which probes with different electrode size and interelectrode spacing were epicardially placed on healthy, fatty, and lesion tissues for measurements. Between 3 electrode sizes (0.1 mm/0.2 mm/0.5 mm) with 3 mm spacing. As indices of capability in gap detection and far-field reduction, in different electrode sizes (0.1 mm/0.2 mm/0.5 mm) and interelectrode spacing (0.1 mm/0.2 mm/0.3 mm/0.5 mm/3 mm) and the optimized electrode size and interelectrode spacing were determined. Compared between PentaRay and the optimal probe determined in study 2. RESULTS: Study 1 demonstrated that unipolar voltage and the duration of EGMs increased as the electrode size increased in any tissue (P < .001). Bipolar EGMs had the same tendency in healthy/fat tissues, but not in lesions. Study 2 showed that significantly higher gap to lesion volume ratio and healthy to fat tissue voltage ratio were provided by a smaller electrode (0.2 mm or 0.3 mm electrode) and smaller spacing (0.1 mm spacing), but 0.3 mm electrode/0.1 mm spacing provided a larger bipolar voltage (P < .05). Study 3 demonstrated that 0.3 mm electrode/0.1 mm spacing provided less deflection with more discrete EGMs (P < .0001) with longer and more reproducible AF cycle length (P < .0001) compared to PentaRay. CONCLUSION: Electrode size affects both unipolar and bipolar EGMs. Catheters with microelectrodes and very small interelectrode spacing may be superior in gap detection and far-field reduction. Importantly, this electrode configuration could dramatically reduce artifactual complex fractionated atrial electrograms and may open a new era for AF mapping.

Sex differences in the origin of Purkinje ectopy-initiated idiopathic ventricular fibrillation.

BACKGROUND: Purkinje ectopics (PurkEs) are major triggers of idiopathic ventricular fibrillation (VF). Identifying clinical factors associated with specific PurkE characteristics could yield insights into the mechanisms of Purkinje-mediated arrhythmogenicity. OBJECTIVE: The purpose of this study was to examine the associations of clinical, environmental, and genetic factors with PurkE origin in patients with PurkE-initiated idiopathic VF. METHODS: Consecutive patients with PurkE-initiated idiopathic VF from 4 arrhythmia referral centers were included. We evaluated demographic characteristics, medical history, clinical circumstances associated with index VF events, and electrophysiological characteristics of PurkEs. An electrophysiology study was performed in most patients to confirm the Purkinje origin. RESULTS: Eighty-three patients were included (mean age 38 ± 14 years; 44 [53%] women), of whom 32 had a history of syncope. Forty-four patients had VF at rest. PurkEs originated from the right ventricle (RV) in 41 patients (49%), from the left ventricle (LV) in 36 (44%), and from both ventricles in 6 (7%). Seasonal and circadian distributions of VF episodes were similar according to PurkE origin. The clinical characteristics of patients with RV vs LV PurkE origins were similar, except for sex. RV PurkEs were more frequent in men than in women (76% vs 24%), whereas LV and biventricular PurkEs were more frequent in women (81% vs 19% and 83% vs 17%, respectively) (P < .0001). CONCLUSION: PurkEs triggering idiopathic VF originate dominantly from the RV in men and from the LV or both ventricles in women, adding to other sex-related arrhythmias such as Brugada syndrome or long QT syndrome. Sex-based factors influencing Purkinje arrhythmogenicity warrant investigation.

Local abnormal ventricular activity detection in scar-related VT: Microelectrode versus conventional bipolar electrode.

BACKGROUND: Conventional bipolar electrodes (CBE) may be suboptimal to detect local abnormal ventricular activities (LAVAs). Microelectrodes (ME) may improve the detection of LAVAs. This study sought to elucidate the detectability of LAVAs using ME compared with CBE in patients with scar-related ventricular tachycardia (VT). METHODS: We included consecutive patients with structural heart disease who underwent radiofrequency catheter ablation for scar-related VT using either of the following catheters equipped with ME: QDOTTM or IntellaTip MIFITM. Detection field of LAVA potentials were classified as three types: Type 1 (both CBE and ME detected LAVA), Type 2 (CBE did not detect LAVA while ME did), and Type 3 (CBE detected LAVA while ME did not). RESULTS: In 16 patients (68 ± 16 years; 14 males), 260 LAVAs electrograms (QDOT = 72; MIFI = 188) were analyzed. Type 1, type 2, and type 3 detections were 70.8% (QDOT, 69.4%; MIFI, 71.3%), 20.0% (QDOT, 23.6%; MIFI, 18.6%) and 9.2% (QDOT, 6.9%; MIFI, 10.1%), respectively. The LAVAs amplitudes detected by ME were higher than those detected by CBE in both catheters (QDOT: ME 0.79 ± 0.50 mV vs. CBE 0.41 ± 0.42 mV, p = .001; MIFI: ME 0.73 ± 0.64 mV vs. CBE 0.38 ± 0.36 mV, p < .001). CONCLUSIONS: ME allow to identify 20% of LAVAs missed by CBE. ME showed higher amplitude LAVAs than CBE. However, 9.2% of LAVAs can still be missed by ME.

Mid-Term Outcomes Following Percutaneous Pulmonary Valve Implantation Using the "Folded Melody Valve" Technique.

BACKGROUND: The folded valve is a manual shortening of the Melody device, which has been validated as a valuable therapeutic option for the management of dysfunctional right ventricular outflow tracts needing a short valved stent. In this article, we aimed to evaluate, in a multicenter cohort, the mid-term outcomes of patients in whom a percutaneous pulmonary valve implantation was performed using the folded valve technique. METHODS: A 2012 to 2018 retrospective multicenter study was performed in 7 European institutions. All patients who benefit from percutaneous pulmonary valve implantation with a folded Melody valve were included. RESULTS: A total of 49 patients (median age, 19 years [range 4­56], 63% male) were included. The primary percutaneous pulmonary valve implantation indication was right ventricular outflow tract stenosis (n=19; 39%), patched native right ventricular outflow tracts were the most common substrate (n=15; 31%). The folded technique was mostly used in short right ventricular outflow tracts (n=28; 57%). Procedural success was 100%. After a median follow-up of 28 months (range, 4­80), folded Melody valve function was comparable to the immediate postimplantation period (mean transvalvular peak velocity=2.6±0.6 versus 2.4±0.6 m/s, P>0.1; only 2 patients had mild pulmonary regurgitation). Incidence rate of valve-related reinterventions was 2.1% per person per year (95% CI, 0.1%­3.9%). The probability of survival without valve-related reinterventions at 36 months was 90% (95% CI, 76%­100%). CONCLUSIONS: The folded Melody valve is a safe technique with favorable mid-term outcomes up to 6.5 years after implantation, comparable with the usual Melody valve implantation procedure. Complications and reinterventions rates were low, making this technique relevant in selected patients.

Marshall bundle elimination, Pulmonary vein isolation, and Line completion for ANatomical ablation of persistent atrial fibrillation (Marshall-PLAN): Prospective, single-center study.

BACKGROUND: Beyond pulmonary vein isolation (PVI), the optimal ablation strategy for persistent atrial fibrillation (AF) remains poorly defined. OBJECTIVE: The purpose of this study was to examine a novel comprehensive ablation strategy (Marshall bundle elimination, Pulmonary vein isolation, and Line completion for ANatomical ablation of persistent atrial fibrillation [Marshall-PLAN]) strictly based on anatomical considerations. METHODS: Left atrial (LA) sites were sequentially targeted as follows: (1) coronary sinus and vein of Marshall (CS-VOM) musculature; (2) PVI; and (3) anatomical isthmuses (mitral, roof, and cavotricuspid isthmus [CTI]). The primary endpoint was 12-month freedom from AF/atrial tachycardia (AT). RESULTS: Seventy-five consecutive patients were included (age 61 ± 9 years; 10 women; AF duration 9 ± 11 months; mean LA volume 197 ± 43 mL). VOM ethanol infusion was completed in 69 patients (92%). The full Marshall-PLAN lesion set (VOM, PVI, mitral, roof, and CTI with block) was successfully completed in 68 patients (91%). At 12 months, 54 of 75 patients (72%) were free from AF/AT after a single procedure (no antiarrhythmic drugs) in the overall cohort. In the subset of patients with a complete Marshall-PLAN lesion set (n = 68), the single procedure success rate was 79%. After 1 or 2 procedures, 67 of 75 patients (89%) remained free from AF/AT (no antiarrhythmic drugs). After 1 or 2 procedures, VOM ethanol infusion was complete in 72 of 75 patients (96%). CONCLUSION: A novel ablation strategy that systematically targets anatomical atrial structures (VOM ethanol infusion, PVI, and prespecified linear lesions) is feasible, safe, and associated with a high rate of freedom from arrhythmia recurrence at 12 months in patients with persistent AF.

Characterization of Complex Atrial Tachycardia in Patients With Previous Atrial Interventions Using High-Resolution Mapping.

OBJECTIVES: This study systematically evaluated mechanisms of atrial tachycardia (AT) by using ultra-high-resolution mapping in a large cohort of patients. BACKGROUND: An incomplete understanding of the mechanism of AT is a major determinant of ablation failure. METHODS: Consecutive patients with ≥1 AT (excluding cavotricuspid isthmus-dependent flutter) were included. Mapping was performed with a 64-pole mapping catheter. The AT mechanism was defined based on activation mapping and confirmed by entrainment in selected cases. RESULTS: A total of 132 patients were included (60 ± 12 years; 31 [23%] female; 111 [84%] previous atrial fibrillation [AF] ablation; 5 [4%] previous left atriotomy). One hundred four (94%) of the 111 post-AF ablation AT patients had substrate-based ablation during the index AF ablation. A total of 214 ATs were mapped, with complete definition of the AT mechanism in 206 (96%). A total of 129 (60%) had anatomic macro-re-entry (circuit diameter 44.2 ± 9.6 mm), 57 (27%) had scar-related localized re-entry (circuit diameter 25.8 ± 12.2 mm), and 20 (9%) had focal AT. Fifty-eight (45%) patients had multiple ATs (27 [20%] dual-loop re-entry; 60 [43%] sequential AT) with complex and highly variable transitions between AT circuits. A total of 116 (90%) of 129 macro-re-entrant ATs, 56 (98%) of 57 localized AT, and 20 (100%) of 20 focal ATs terminated after radiofrequency ablation. After a mean follow-up of 13 ± 9 months, 57 (46%) patients experienced recurrence of AT. CONCLUSIONS: Among patients with AT in the context of previous atrial interventions, particularly post-AF ablation patients, multiple complex AT circuits are common. Despite complete delineation of arrhythmia circuits using ultra-high-resolution mapping and high acute ablation success rates, long-term freedom from AT is modest.

Acute and mid-term outcome of ethanol infusion of vein of Marshall for the treatment of perimitral flutter.

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.

Electrogram morphology discriminators in implantable cardioverter defibrillators: A comparative evaluation.

BACKGROUND: Morphology algorithms are currently recommended as a standalone discriminator in single-chamber implantable cardioverter defibrillators (ICDs). However, these proprietary algorithms differ in both design and nominal programming. OBJECTIVE: To compare three different algorithms with nominal versus advanced programming in their ability to discriminate between ventricular (VT) and supraventricular tachycardia (SVT). METHODS: In nine European centers, VT and SVTs were collected from Abbott, Boston Scientific, and Medtronic dual- and triple-chamber ICDs via their respective remote monitoring portals. Percentage morphology matches were recorded for selected episodes which were classified as VT or SVT by means of atrioventricular comparison. The sensitivity and related specificity of each manufacturer discriminator was determined at various values of template match percentage from receiving operating characteristics (ROC) curve analysis. RESULTS: A total of 534 episodes were retained for the analysis. In ROC analyses, Abbott Far Field MD (area under the curve [AUC]: 0.91; P < .001) and Boston Scientific RhythmID (AUC: 0.95; P < .001) show higher AUC than Medtronic Wavelet (AUC: 0.81; P < .001) when tested for their ability to discriminate VT from SVT. At nominal % match threshold all devices provided high sensitivity in VT identification, (91%, 100%, and 90%, respectively, for Abbott, Boston Scientific, and Medtronic) but contrasted specificities in SVT discrimination (85%, 41%, and 62%, respectively). Abbott and Medtronic's nominal thresholds were similar to the optimal thresholds. Optimization of the % match threshold improved the Boston Scientific specificity to 79% without compromising the sensitivity. CONCLUSION: Proprietary morphology discriminators show important differences in their ability to discriminate SVT. How much this impact the overall discrimination process remains to be investigated.

Heart rate response during exercise predicts exercise tolerance in adults with transposition of the great arteries and atrial switch operation.

BACKGROUND: To assess the relationship between heart rate response and exercise tolerance in adults with systemic right ventricle (sRV) after atrial switch repair for Transposition of the Great Artery (TGA) in addition to other physiological parameters. METHODS: All patients with a sRV after atrial switch repair for TGA followed in our institution between June 2015 and April 2018 who underwent cardiopulmonary exercise testing (CPET) were analyzed. Cardiac imaging performed within a six-month time period of the CPET were also collected. Chronotropic incompetence was defined as the inability to achieve 80% of age-predicted maximal heart rate reserve (HRR) and <62% on a beta-blocker regimen. Patient characteristics were assessed according to tertiles of the percentage of predicted pVO2 (%ppVO2). RESULTS: We studied 70 patients (mean of age 32.4 ±â€¯7.6 years old, 51 males). Mean peak oxygen uptake was 21.5 ±â€¯5.8 mL/kg/min, corresponding to a %ppVO2 of 57 ±â€¯14.1% while mean VE/VCO2 slope was 37.1 ±â€¯8.2. There was a trend toward more exaggerated hyperventilation in patient with lower pVO2. Mean age-adjusted HRR was 68.5 ±â€¯19%. Chronotropic incompetence was observed in 65.7% and was correlated with %ppVO2 (r = 0.482; p < 0.001) as physical training evaluated with Ventilatory Anaerobic threshold (r = 0.571; p < 0.001), while no difference was found based on respiratory parameters. No echocardiographic or Magnetic Resonance Imaging parameters assessing sRV systolic function at rest were correlated with %ppVO2. CONCLUSIONS: Exercise limitation is related to the inability to increase cardiac output during exercise and is notably due to the degree of chronotropic incompetence.

A Glanzmann thrombasthenia family associated with a TUBB1-related macrothrombocytopenia.

BACKGROUND: Macrothrombocytopenia (MTP) is a rare but enigmatic complication of Glanzmann thrombasthenia (GT), an inherited bleeding disorder caused by the absence of platelet aggregation due to deficiencies of the αIIbß3 integrin. OBJECTIVES: We report a family with type I GT and a prolonged bleeding time but unusually associated with congenital mild thrombocytopenia and platelet size heterogeneity with giant forms. METHODS AND RESULTS: Sanger sequencing of DNA from the propositus identified 2 heterozygous ITGB3 gene mutations: p.P189S and p.C210S both of which prevent αIIbß3 expression and are causative of GT but without explaining the presence of enlarged platelets. High-throughput screening led to the detection of a predicted disease-causing heterozygous mutation in the TUBB1 gene: p.G146R, encoding ß1-tubulin, a component of the platelet cytoskeleton and a gene where mutations are a known cause of MTP. CONCLUSIONS: Family screening confirmed that this rare phenotype results from oligogenic inheritance while suggesting that the GT phenotype dominates clinically.

Post-Myocardial Infarction Scar With Fat Deposition Shows Specific Electrophysiological Properties and Worse Outcome After Ventricular Tachycardia Ablation.

Background Fat deposition (FD) is part of the healing process after myocardial infarction. The characteristics of FD and its impact on the outcome in patients undergoing ventricular tachycardia (VT) ablation have not been thoroughly studied. Methods and Results We studied consecutive patients undergoing post-myocardial infarction VT ablation with pre-procedural cardiac computed tomography. FD was defined as intra-myocardial attenuation ≤ -30 HU on computed tomography. Clinical, anatomical, and post-procedural outcome was assessed in the overall population. Electrophysiological characteristics were assessed is a subgroup of patients with high-density electro-anatomical maps. Sixty-nine patients were included (66±12 years). FD was detected in 44 (64%) patients. The presence of FD related to scar age (odds ratio [OR]: 1.14 per year; P=0.001) and scar extent (OR: 1.27 per segment; P=0.02). On electro-anatomical maps, FD was characterized by lower bipolar amplitude (P<0.001) and prolonged electrogram duration (P<0.001). Although the proportion of local abnormal ventricular activation was similar (P=0.22), local abnormal ventricular activation showed lower amplitude (P<0.001) and were more delayed (P<0.001) in scars with FD. After a mean follow-up of 26 months, patients with FD experienced a worse outcome including all-cause mortality and VT recurrence (70% versus 28%, P log rank=0.009). On multivariate analysis, FD (hazard ratio=2.69; 95% CI, 1.12-6.46; P=0.027) and left ventricular systolic dysfunction (hazard ratio=2.57; 95% CI, 1.13-5.85; P=0.024) were independent predictors of adverse outcomes. Conclusions FD in patients with post-myocardial infarction VT undergoing catheter ablation relates to scar age and size and may be a marker of adverse outcomes including all-cause mortality and VT recurrence.

Impact of Spacing and Orientation on the Scar Threshold With a High-Density Grid Catheter.

BACKGROUND: Multipolar catheters are increasingly used for high-density mapping. However, the threshold to define scar areas has not been well described for each configuration. We sought to elucidate the impact of bipolar spacing and orientation on the optimal threshold to match magnetic resonance imaging-defined scar. METHOD: The HD-Grid catheter uniquely allows for different spatially stable bipolar configurations to be tested. We analyzed the electrograms with settings of HD-16 (3 mm spacing in both along and across bipoles) and HD-32 (1 mm spacing in along bipoles and 3 mm spacing in across bipoles) and determined the optimal cutoff for scar detection in 6 infarcted sheep. RESULTS: From 456 total acquisition sites (mean 76±12 per case), 14 750 points with the HD-16 and 32286 points with the HD-32 configuration for bipolar electrograms were analyzed. For bipolar voltages, the optimal cutoff value to detect the magnetic resonance imaging-defined scar based on the Youden's Index, and the area under the receiver operating characteristic curve (AUROC) differed depending on the spacing and orientation of bipoles; across 0.84 mV (AUROC, 0.920; 95% CI, 0.911-0.928), along 0.76 mV (AUROC, 0.903; 95% CI, 0.893-0.912), north-east direction 0.95 mV (AUROC, 0.923; 95% CI, 0.913-0.932), and south-east direction, 0.87 mV (AUROC, 0.906; 95% CI, 0.895-0.917) in HD-16; and across 0.83 mV (AUROC, 0.917; 95% CI, 0.911-0.924), along 0.46 mV (AUROC, 0.890; 95% CI, 0.883-0.897), north-east direction 0.89 mV (AUROC, 0.923; 95% CI, 0.917-0.929), and south-east direction 0.83 mV (AUROC, 0.913; 95% CI, 0.906-0.920) in HD-32. Significant differences in AUROC were seen between HD-16 along versus across (P=0.002), HD-16 north-east direction versus south-east direction (P=0.01), HD-32 north-east direction versus south-east direction (P<0.0001), and HD-16 along versus HD-32 along (P=0.006). The AUROC was significantly larger (P<0.01) when only the best points on each given site were selected for analysis, compared with when all points were used. CONCLUSIONS: Spacing and orientation of bipoles impacts the accuracy of scar detection. Optimal threshold specific to each bipolar configuration should be determined. Selecting one best voltage point among multiple points projected on the same surface is also critical on the Ensite-system to increase the accuracy of scar-mapping.

Noninvasive Mapping and Electrocardiographic Imaging in Atrial and Ventricular Arrhythmias (CardioInsight).

Electrocardiographic imaging is a mapping technique aiming to noninvasively characterize cardiac electrical activity using signals collected from the torso to reconstruct epicardial potentials. Its efficacy has been demonstrated clinically, from mapping premature ventricular complexes and accessory pathways to of complex arrhythmias. Electrocardiographic imaging uses a standardized workflow. Signals should be checked manually to avoid automatic processing errors. Reentry is confirmed in the presence of local activation covering the arrhythmia cycle length. Focal breakthroughs demonstrate a QS pattern associated with centrifugal activation. Electrocardiographic imaging offers a unique opportunity to better understand the mechanism of cardiac arrhythmias and guide ablation.

Long-Term Follow-Up of Idiopathic Ventricular Fibrillation in a Pediatric Population: Clinical Characteristics, Management, and Complications.

Background The natural history and long-term outcome in pediatric patients with idiopathic ventricular fibrillation ( IVF ) are poorly characterized. We sought to define the clinical characteristics and long-term outcomes of a pediatric cohort with an initial diagnosis of IVF . Methods and Results Patients were included from an International Registry of IVF (consisting of 496 patients). Inclusion criteria were: (1) VF with no identifiable cause following comprehensive analysis for ischemic, electrical or structural heart disease and (2) age ≤16 years. These included 54 pediatric IVF cases (age 12.7±3.7 years, 59% male) among whom 28 (52%) had a previous history of syncope (median 2 syncopal episodes [interquartile range 1]). Thirty-six (67%) had VF in situations associated with high adrenergic tone. During a median 109±12 months of follow-up, 31 patients (57%) had recurrence of ventricular arrhythmias, mainly VF . Two patients developed phenotypic expression of an inherited arrhythmia syndrome during follow-up (hypertrophic cardiomyopathy and long QT syndrome, respectively). A total of 15 patients had positive genetic testing for inherited arrhythmia syndromes. Ten patients (18%) experienced device-related complications. Three patients (6%) died, 2 due to VF storm. Conclusions In pediatric patients with IVF , a minority develop a definite clinical phenotype during long-term follow-up. Recurrent VF is common in this patient group.