Ablation of atrioventricular-nodal-reentrant- tachycardia in a patient with left-sided superior vena cava and dilated coronary sinus.

Atrioventricular (AV)-nodal-reentrant-tachycardia is a rare association in a patient with persistent left-sided superior vena cava and dilated coronary sinus. There are a few inherent difficulties in ablation in this condition, viz., difficulty in localization of good site for ablation and difficulty in stabilization of the ablation catheter at the designated site, making it difficult to produce transmural lesions and increasing risk of producing AV block. We hereby present a case highlighting the difficulties and possible solutions for them.

Atrial tachycardia from an unusual site-Left atrial appendage tachycardia: Challenges in ablation.

Left atrial appendage (LAA) tachycardia are rarely encountered in clinical practice (2.1% of focal atrial tachycardia). Out of these, the ones arising from the distal part of LAA are difficult to ablate due to higher risk of LAA perforation and thromboembolism. We hereby present a patient with LAA tachycardia mapped to the tip of LAA with the help of the CARTO system and ablated. This case highlights the inherent challenges faced in such a scenario.

DNA copy number aberrations in small-cell lung cancer reveal activation of the focal adhesion pathway.

Small-cell lung cancer (SCLC) is the most aggressive subtype of lung cancer in its clinical behavior, with a 5-year overall survival as low as 5%. Despite years of research in the field, molecular determinants of SCLC behavior are still poorly understood, and this deficiency has translated into an absence of specific diagnostics and targeted therapeutics. We hypothesized that tumor DNA copy number alterations would allow the identification of molecular pathways involved in SCLC progression. Array comparative genomic hybridization was performed on DNA extracted from 46 formalin-fixed paraffin-embedded SCLC tissue specimens. Genomic profiling of tumor and sex-matched control DNA allowed the identification of 70 regions of copy number gain and 55 regions of copy number loss. Using molecular pathway analysis, we found a strong enrichment in these regions of copy number alterations for 11 genes associated with the focal adhesion pathway. We verified these findings at the genomic, gene expression and protein level. Focal Adhesion Kinase (FAK), one of the central genes represented in this pathway, was commonly expressed in SCLC tumors and constitutively phosphorylated in SCLC cell lines. Those were poorly adherent to most substrates but not to laminin-322. Inhibition of FAK phosphorylation at Tyr(397) by a small-molecule inhibitor, PF-573,228, induced a dose-dependent decrease of adhesion and an increase of spreading in SCLC cell lines on laminin-322. Cells that tended to spread also showed a decrease in focal adhesions, as demonstrated by a decreased vinculin expression. These results support the concept that pathway analysis of genes in regions of copy number alterations may uncover molecular mechanisms of disease progression and demonstrate a new role of FAK and associated adhesion pathways in SCLC. Further investigations of FAK at the functional level may lead to a better understanding of SCLC progression and may have therapeutic implications.

Repeated fracture of pacemaker leads with migration into the pulmonary circulation and temporary pacemaker wire insertion via the azygous vein.

Repeated implantation of pacemaker in the same patient is a common occurrence because of the increased longevity of patients. However, repeated lead fracture in the same patient and migration of the pacemaker lead into the pulmonary circulation is rare. We describe a 56-year-old gentleman who had undergone pacemaker implantations thrice due to repeated lead fractures (thrice) and also had migration of the pacemaker lead into the pulmonary circulation. He also had an azygous vein which was noticed while placing the temporary pacemaker wire.