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AIMS Radiofrequency catheter ablation of atrial fibrillation (AF) is one of the most complex ablation procedures. Both patients and operators are exposed to scattered radiation. This study evaluated the safety and efficacy of intracardiac echo (ICE)-guided pulmonary vein isolation (PVI) without fluoroscopy. METHODS We retrospectively analyzed the data of 481 consecutive patients with paroxysmal AF undergoing radiofrequency PVI with the CARTO 3 system (Biosense Webster, Diamond Bar, CA, USA). ICE-guided PVI without fluoroscopy and without CT/MRI integration (Nonfluoro group) was performed for 245 patients, and conventional fluoroscopy-guided PVI (Fluoro group) was performed for 236 patients. The primary safety endpoint was the incidence of major adverse events. The primary efficacy endpoint was freedom from AF during follow-up. Secondary endpoints included procedure duration, fluoroscopy duration, and acute PVI rate. RESULTS Mean procedure times between groups were similar (108.8 ± 18.2 minutes in the Non-fluoro group vs 113.6 ± 26.8 minutes in the Fluoro group; P = not significant [NS]). Acute PVI was achieved in all patients, with mean radiofrequency application times of 43.4 ± 7.5 and 44.4 ± 10.7 minutes for the Nonfluoro and Fluoro groups, respectively (P = NS). The incidence of cardiac tamponade was 1.2% (3/245 patients) in the Nonfluoro group and 0.8% (2/236 patients) in the Fluoro group (P = NS). During 15.2 ± 4.1 months of follow-up, after a single procedure, AF recurrence was documented in 65 of 245 (26.5%) patients and 61 of 236 (25.8%) patients in the Nonfluoro and Fluoro groups, respectively (P = NS). CONCLUSIONS Nonfluoroscopic ICE-guided catheter ablation of AF without prior cardiac image integration or angiography is feasible and safe. PVI without fluoroscopy did not affect procedure duration or long-term efficacy.

Purpose Atrial fibrillation (AF) is the most common cardiac arrhythmia in clinical practice and is associated with considerable morbidity and mortality. Multiple genes and genetic loci affecting AF susceptibility have been identified using positional cloning and candidate gene approaches The extent to which such polymorphisms contribute to AF is unknown. The aim of this study was to determine the spectrum and prevalence of rare amino acid coding (AAC) variants in candidate AF genes in a cohort of unrelated AF patients from Kazakhstan. Methods We sequenced 96 candidate genes in 102 Kazakhstani patients with AF using customized targeted gene panel (Haloplex, Agilent Technologies). Variants detected were compared with variants observed in the Exome Sequencing Project (ESP) to identify very rare (minor allele frequency 0.04%) AAC variants. ACMG/AMP guidelines were applied for variant interpretation of clinical significance - pathogenic (P), possibly pathogenic (PP), variant of uncertain significance (VUS), possibly benign (PB), benign (B). The ClinVar, Varsome and HGMD databases were also used. Results Median age at AF onset was 47.0 years, and 31.3% had a family history of AF. Totally 456 variants were identified in 74 genes for the overall study group. Variants included one in/del variant, four splice-site variants and 451 single-nucleotide variants (SNV) within the coding exonic regions. 168 HGMD mutations (61 unique) were observed in 37 genes. Classification of 456 variants according to ACMG guidelines showed that 13(2.9%) variants were classified as pathogenic, 13(2.9%) - likely pathogenic, 145 (31.9%) - uncertain significance, 109 (23.8%) likely benign and 175 (38.4%) benign. 31 rare AAC variants were identified in 20 of 102 AF patients. Among them three pathogenic variants KCNQ1 c.477+1G>A, KCNJ2 R218Q and KCNE2 T10K C29A (PP) were identified. Conclusion Our study shows that individuals presenting with AF carry rare mutations and potentially pathogenetic sequence variants in classical cardiac risk genes in almost 20%. No very rare AAC variants were identified in 80% of AF patients. Potential reasons for the lack of very rare AAC variants include a complex pattern of inheritance, variants in as yet unidentified AF genes or in noncoding regions, and environmental factors.

Purpose Ventricular fibrillation (VF) and ventricular tachycardia (VT) are major causes of sudden cardiac death. In some cases clinical investigations fail to identify the underlying cause and the event is classified as idiopathic (iVT). Recent achievements in molecular genetics has unveiled the complex molecular basis of many cardiac conditions, paving the way for routine use of gene testing in clinical practice. In current practice, genetic testing can be used in a clinically affected patient to confirm diagnosis, or to formulate a differential diagnosis among overlapping phenotypes or between hereditary and acquired (nongenetic) forms of disease. We aimed to identify genetic variants potentially contributing to the life-threatening arrhythmias using targeted next-generation sequencing (NGS) approach in Kazakhstani patients with arrhythmias. Methods The study included 92 Kazakhstani patients (mean age of 31.2 years at the time of the VT event), diagnosed with iVT, VT and coronary heart disease (CHD), VT and dilated cardiomyopathy (DCM). We developed a targeted panel of 96 known cardiac disease genes, associated with cardiomyopathy and arrhythmia. Results We observed 168 mutations (61 distinct) listed in the Human Genome Mutation Database and another 256 rare/unique variants with elevated pathogenic potential. Also we analyzed observed mutations according to ACMG guidelines. The majority of VT/CHD patients carried known mutations and rare variants with high pathogenetic potential in the same genes and at a comparable frequency as observed for VT/DCM and iVT patients. The most abundant mutations observed for the CHD group locate to MYBPC3, DMD, LAMA2, MYH6 and GAA. A subset of patients originally diagnosed with iVT carry clinically-relevant variants in genes associated with cardiac channelopathies and cardiomyopathies. Conclusion Our study indicates that individuals presenting with VT either secondary to CHD, DCM or of idiopathic etiology carry multiple rare mutations and potentially pathogenic sequence variants in classical cardiac risk genes in a similar pattern and at a comparable frequency. Molecular genetic testing of patients with life-threatening ventricular arrhythmia with NGS identifies a molecular-genetic cause in a significant proportion of patients.

Introduction: Cardiac arrhythmias are the most common cause of mortality and sudden cardiac death worldwide. In the past decade, genetic factors underlying arrhythmogenic diseases have been revealed and given novel insights in to the understanding and treatment of arrhythmias predisposing one to sudden cardiac death.Material and methods: We conducted a pilot genetic screening of two patients with catecholaminergic polymorphic ventricular tachycardia (CPVT) and 14 patients with ventricular tachycardia (VT) for genetic variants in the human ryanodine receptor gene 2 (hRYR2). The most relevant 45 hot-spot exons of hRYR2 were amplified by polymerase chain reaction (PCR) and directly sequenced.Results: One novel mutation in a CPVT patient (c.A13892T; p.D4631V) and a novel mutation in a VT patient (c.G5428C; p.V1810L) were identified. Both variants are located at phylogenetically conserved positions and predicted pathogenesis. Three known synonymous SNPs (rs3765097, rs2253273, and TMP ESp1 237664067) were detected in the study group. No further variants within the target regions were detected in the study group.Conclusion: The results of study can be applied to risk asssessment for life-threatening arrhythmias and assist in development of appropriate strategies for prevention of sudden cardiac death. The implementation of these strategies would assist in the management of patients with genetically determined arrhythmias in Kazakhstan.

The case describes successful cryoablation of para-Hisian accessory pathway in adolescent.