The IC-D score for predicting prophylactic cardioverter-defibrillator implantation following acute myocardial infarction.

BACKGROUND: A reduced left ventricular ejection fraction (LVEF) ≤35% ≥6 weeks following an acute myocardial infarction (MI) may indicate prophylactic implantation of a cardioverter-defibrillator (ICD). We sought to find predictors of absence of significant left ventricular (LV) remodeling post-MI. METHODS: All consecutive patients hospitalized for acute MI with an LVEF ≤35% at discharge in our institution from 2010 were retrospectively included. Patients were assigned to two groups according to the persistence of an LVEF ≤35% (ICD+) or a recovery >35% (ICD-). Logistic regression was performed to build a predictive score, which was then externally validated. RESULTS: Among a total of 1533 consecutive MI patients, 150 met inclusion criteria, 53 (35%) in the ICD+ group and 97 in the ICD group. After multivariable analyses, an LVEF ≤25% at discharge (adjusted OR 6.23 [2.47 to 17.0], p < .0001) and a CPK peak at the MI acute phase >4600 UI/L (adjusted OR 9.99 [4.27 to 25.3], p < .0001) both independently predicted non-recovery at 6 weeks. The IC-D (Increased Cpk-LV Dysfunction) score predicted persistent LVEF ≤35% with areas under curve of 0.83 and 0.73, in the study population and in a multicenter validation cohort of 150 patients, respectively (p < .0001). CONCLUSIONS: The association of a severely reduced LVEF and a major release of myocardial necrosis biomarkers at the acute phase of MI predict unfavorable remodeling, and prophylactic ICD implantation.

Evaluation of left atrial linear ablation using contiguous and optimized radiofrequency lesions: the ALINE study.

Aims: Achieving block across linear lesions is challenging. We prospectively evaluated radiofrequency (RF) linear ablation at the roof and mitral isthmus (MI) using point-by-point contiguous and optimized RF lesions. Methods and results: Forty-one consecutive patients with symptomatic persistent AF underwent stepwise contact force (CF)-guided catheter ablation during ongoing AF. A single linear set of RF lesions was delivered at the roof and posterior MI according to the 'Atrial LINEar' (ALINE) criteria, i.e. point-by-point RF delivery (up to 35 W) respecting strict criteria of contiguity (inter-lesion distance ≤ 6 mm) and indirect lesion depth assessment (ablation index ≥550). We assessed the incidence of bidirectional block across both lines only after restoration of sinus rhythm. After a median RF time of 7 min [interquartile range (IQR) 5-9], first-pass block across roof lines was observed in 38 of 41 (93%) patients. Final bidirectional roof block was achieved in 40 of 41 (98%) patients. First-pass block was observed in 8 of 35 (23%) MI lines, after a median RF time of 8 min (IQR 7-12). Additional endo- and epicardial (54% of patients) RF applications resulted in final bidirectional MI block in 28 of 35 (80%) patients. During a median follow-up of 396 (IQR 310-442) days, 12 patients underwent repeat procedures, with conduction recovery in 4 of 12 and 5 of 10 previously blocked roof lines and MI lines, respectively. No complications occurred. Conclusion: Anatomical linear ablation using contiguous and optimized RF lesions results in a high rate of first-pass block at the roof but not at the MI. Due to its complex 3D architecture, the MI frequently requires additional endo- and epicardial RF lesions to be blocked.

Contribution of exome sequencing for genetic diagnostic in arrhythmogenic right ventricular cardiomyopathy/dysplasia.

BACKGROUND: Arrhythmogenic Right Ventricular Cardiomyopathy/Dysplasia (ARVC/D) is an inherited cardiomyopathy mainly caused by heterozygous desmosomal gene mutations, the major gene being PKP2. The genetic cause remains unknown in ~50% of probands with routine desmosomal gene screening. The aim of this study was to assess the diagnostic accuracy of whole exome sequencing (WES) in ARVC/D with negative genetic testing. METHODS: WES was performed in 22 patients, all without a mutation identified in desmosomal genes. Putative pathogenic variants were screened in 96 candidate genes associated with other cardiomyopathies/channelopathies. The sequencing coverage depth of PKP2, DSP, DSG2, DSC2, JUP and TMEM43 exons was compared to the mean coverage distribution to detect large insertions/deletions. All suspected deletions were verified by real-time qPCR, Multiplex-Ligation-dependent-Probe-Amplification (MLPA) and cGH-Array. MLPA was performed in 50 additional gene-negative probands. RESULTS: Coverage-depth analysis from the 22 WES data identified two large heterozygous PKP2 deletions: one from exon 1 to 14 and one restricted to exon 4, confirmed by qPCR and MLPA. MLPA identified 2 additional PKP2 deletions (exon 1-7 and exon 1-14) in 50 additional probands confirming a significant frequency of large PKP2 deletions (5.7%) in gene-negative ARVC/D. Putative pathogenic heterozygous variants in EYA4, RBM20, PSEN1, and COX15 were identified in 4 unrelated probands. CONCLUSION: A rather high frequency (5.7%) of large PKP2 deletions, undetectable by Sanger sequencing, was detected as the cause of ARVC/D. Coverage-depth analysis through next-generation sequencing appears accurate to detect large deletions at the same time than conventional putative mutations in desmosomal and cardiomyopathy-associated genes.

Is Mapping of Complex Fractionated Electrograms Obsolete?

Atrial fibrillation is the most common clinically encountered arrhythmia and catheter ablation has emerged as a viable treatment option in drug-refractory cases. Pulmonary vein isolation is widely regarded as the cornerstone for successful outcomes in paroxysmal AF given that the pulmonary veins are a frequent source of AF triggering. Ablation strategies for persistent AF are less well defined. Mapping and ablation of complex fractionated electrograms (CFAEs) is one strategy that has been proposed as a means of modifying the atrial substrate thought to be critical to the perpetuation of AF. Results of clinical studies have proved conflicting and there are now strong data to suggest that pulmonary vein isolation alone is associated with outcomes comparable to those of pulmonary vein isolation plus CFAE ablation. Several studies have demonstrated that the majority of CFAEs are passive phenomena and therefore not critical to the perpetuation of AF. Conventional mapping technologies (using a bipolar or circular mapping catheter) lack the spatiotemporal resolution to identify mechanisms of AF persistence. The development of wide-field mapping techniques allows simultaneous acquisition of activation data over large areas. This strategy has the potential to better identify regions critical to AF perpetuation, and preliminary data suggest that ablation outcomes are improved when guided by these techniques. While mapping and ablation of all CFAEs is almost certainly obsolete, better identification of regions responsible for AF persistence has the potential to improve outcomes in ablation of persistent AF.