LMNA-related heart disease was associated with a high incidence of phenotypic progression and adverse arrhythmic and nonarrhythmic events over long-term follow-up. The index cardiac phenotype did not predict adverse events. Genetic diagnosis and subsequent follow-up, including anticipatory planning for therapies to prevent sudden death and manage HF, is warranted.

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OBJECTIVES This study sought to assess the relationship between fibrosis and re-entrant activity in persistent atrial fibrillation (AF). BACKGROUND The mechanisms involved in sustaining re-entrant activity during AF are poorly understood. METHODS Forty-one patients with persistent AF (age 56 ± 12 years; 6 women) were evaluated. High-resolution electrocardiographic imaging (ECGI) was performed during AF by using a 252-chest electrode array, and phase mapping was applied to locate re-entrant activity. Sites of high re-entrant activity were defined as re-entrant regions. Late gadolinium-enhanced (LGE) cardiac magnetic resonance (CMR) was performed at 1.25 × 1.25 × 2.5 mm resolution to characterize atrial fibrosis and measure atrial volumes. The relationship between LGE burden and the number of re-entrant regions was analyzed. Local LGE density was computed and characterized at re-entrant sites. All patients underwent catheter ablation targeting re-entrant regions, the procedural endpoint being AF termination. Clinical, CMR, and ECGI predictors of acute procedural success were then analyzed. RESULTS Left atrial (LA) LGE burden was 22.1 ± 5.9% of the wall, and LA volume was 74 ± 21 ml/m2. The number of re-entrant regions was 4.3 ± 1.7 per patient. LA LGE imaging was significantly associated with the number of re-entrant regions (R = 0.52, p = 0.001), LA volume (R = 0.62, p < 0.0001), and AF duration (R = 0.54, p = 0.0007). Regional analysis demonstrated a clustering of re-entrant activity at LGE borders. Areas with high re-entrant activity showed higher local LGE density as compared with the remaining atrial areas (p < 0.0001). Failure to achieve AF termination during ablation was associated with higher LA LGE burden (p < 0.001), higher number of re-entrant regions (p < 0.001), and longer AF duration (p = 0.008). CONCLUSIONS The number of re-entrant regions during AF relates to the extent of LGE on CMR, with the location of these regions clustering to LGE areas. These characteristics affect procedural outcomes of ablation.

Background: An accurate estimation of the risk of life-threatening (LT) ventricular tachyarrhythmia (VTA) in patients with LMNA mutations is crucial to select candidates for implantable cardioverter defibrillator (ICD) implantation. Methods: We included 839 adult patients with LMNA mutations, including 660 from a French nationwide registry in the development sample, and 179 from other countries, referred to 5 tertiary centers for cardiomyopathies, in the validation sample. LTVTA was defined as a) sudden cardiac death or b) ICD-treated or hemodynamically unstable VTA. The prognostic model was derived using Fine-Gray's regression model. The net reclassification was compared with current clinical practice guidelines. The results are presented as means (standard deviation) or medians [interquartile range]. Results: We included 444 patients 40.6 (14.1) years of age in the derivation sample and 145 patients 38.2 (15.0) years in the validation sample, of whom 86 (19.3%) and 34 (23.4%) suffered LTVTA over 3.6 [1.0-7.2] and 5.1 [2.0-9.3] years of follow-up, respectively. Predictors of LTVTA in the derivation sample were: male sex, non-missense LMNA mutation, 1st degree and higher atrioventricular block, non-sustained ventricular tachycardia, and left ventricular ejection fraction. In the derivation sample, C-index (95% CI) of the model was 0.776 (0.711-0.842) and calibration slope 0.827. In the external validation sample, the C-index was 0.800 (0.642-0.959) and calibration slope 1.082 (95% CI, 0.643-1.522). A 5-year estimated risk threshold ≥7% predicted 96.2% of LTVTA and net reclassified 28.8% of patients with LTVTA compared with the guidelines-based approach. Conclusions: Compared to the current standard of care, this risk prediction model for LTVTA in laminopathies facilitated significantly the choice of ICD candidates. Clinical Trial Registration: URL: https://www.clinicaltrials.gov. Unique Identifier: NCT03058185.

Background— Lamin A/C ( LMNA ) cardiomyopathy is a genetic disease with a proclivity for ventricular arrhythmias. We describe the multicenter experience with percutaneous catheter ablation of sustained monomorphic ventricular tachycardia (VT) in LMNA cardiomyopathy. Methods and Results— Twenty-five consecutive LMNA mutation patients from 4 centers were included (mean age, 55±9 years; ejection fraction, 34±12%; VT storm in 36%). Complete atrioventricular block was present in 11 patients; 3 patients were on mechanical circulatory support for severe heart failure. A median of 3 VTs were inducible per patient; in 82%, mapping was consistent with origin from scar in the basal left ventricle, particularly the septum, but also basal inferior wall and subaortic mitral continuity. After multiple procedures (median 2/patient; transcoronary alcohol in 6 and surgical cryoablation in 2 patients), acute success (noninducibility of any VT) was achieved in only 25% of patients. Partial success (inducibility of a nonclinical VT only: 50%) and failure (persistent inducibility of clinical VT: 12.5%) was attributed to intramural septal substrate in 13 of 18 patients (72%). Complications occurred in 25% of patients. After a median follow-up of 7 months after the last procedure, 91% experienced ≥1 VT recurrence, 44% received or were awaiting mechanical circulatory support or transplant for end-stage heart failure, and 26% died. Conclusions— Catheter ablation of VT associated with LMNA cardiomyopathy is associated with poor outcomes including high rate of arrhythmia recurrence, progression to end-stage heart failure, and high mortality. Basal septal scar and intramural VT origin makes VT ablation challenging in this population.

Multipolar mapping catheters with small electrodes provide more accurate and higher density maps, with a higher sensitivity to near-field signals. Agreement between PR and NAV is low.

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Background— During the past years, many innovations have been introduced to facilitate catheter ablation of post–myocardial infarction ventricular tachycardia. However, the predictors of outcome after ablation were not thoroughly studied. Methods and Results— From 2009 to 2013, consecutive patients referred for post–myocardial infarction ventricular tachycardia ablation were included. The end point of the procedure was complete elimination of local abnormal ventricular activities (LAVA) and ventricular tachycardia (VT) noninducibility. The predictors of outcome with primary end point of VT recurrence were assessed. A total of 125 patients were included (age: 64±11 years; 7 women) for 142 procedures. The left ventricle was accessed via transseptal, retrograde aortic, and epicardial approaches in 87%, 33%, and 37% of patients, respectively. Three-dimensional electroanatomical mapping system was used in 70%, multipolar catheter in 51%, and real-time image integration in 38% (from magnetic resonance imaging in 39% and multidetector computed tomography in 93%) of patients. Before ablation, VT was inducible in 75%, and endocardial/epicardial LAVA were present in 88%/75%. After ablation, complete LAVA elimination was achieved in 60%, and VT noninducibility in 83%. During a median follow-up of 850 days (interquartile range, 439–1707), VT recurrence was observed in 36%. Multivariable analysis identified 3 independent outcome predictors: the ability to achieve complete LAVA elimination ( R 2 =0.29; P <0.0001; risk ratio=0.52 [0.38–0.70]), the use of real-time image integration ( R 2 =0.21; P =0.0006; risk ratio=0.49 [0.33–0.74]), and the use of multipolar catheters ( R 2 =0.08; P =0.05; risk ratio=0.75 [0.56–1.00]). Conclusions— Achievement of complete LAVA elimination and use of scar integration from imaging and multipolar catheters to focus high-density mapping are independent predictors of VT-free survival after catheter ablation for post–myocardial infarction ventricular tachycardia.