Epicardial phrenic nerve displacement during catheter ablation of atrial and ventricular arrhythmias: procedural experience and outcomes.

BACKGROUND Arrhythmia origin in close proximity to the phrenic nerve (PN) can hinder successful catheter ablation. We describe our approach with epicardial PN displacement in such instances. METHODS AND RESULTS PN displacement via percutaneous pericardial access was attempted in 13 patients (age 49±16 years, 9 females) with either atrial tachycardia (6 patients) or atrial fibrillation triggered from a superior vena cava focus (1 patient) adjacent to the right PN or epicardial ventricular tachycardia origin adjacent to the left PN (6 patients). An epicardially placed steerable sheath/4 mm-catheter combination (5 patients) or a vascular or an esophageal balloon (8 patients) was ultimately successful. Balloon placement was often difficult requiring manipulation via a steerable sheath. In 2 ventricular tachycardia cases, absence of PN capture was achieved only once the balloon was directly over the ablation catheter. In 3 atrial tachycardia patients, PN displacement was not possible with a balloon; however, a steerable sheath/catheter combination was ultimately successful. PN displacement allowed acute abolishment of all targeted arrhythmias. No PN injury occurred acutely or in follow up. Two patients developed acute complications (pleuro-pericardial fistula 1 and pericardial bleeding 1). Survival free of target arrhythmia was achieved in all atrial tachycardia patients; however, a nontargeted ventricular tachycardia recurred in 1 patient at a median of 13 months' follow up. CONCLUSIONS Arrhythmias originating in close proximity to the PN can be targeted successfully with PN displacement with an epicardially placed steerable sheath/catheter combination, or balloon, but this strategy can be difficult to implement. Better tools for phrenic nerve protection are desirable.

Immunization with a circumsporozoite epitope fused to Bordetella pertussis adenylate cyclase in conjunction with cytotoxic T-lymphocyte-associated antigen 4 blockade confers protection against Plasmodium berghei liver-stage malaria

The adenylate cyclase toxoid (ACT) of Bordetella pertussis is capable of delivering its N-terminal catalytic domain into the cytosol of CD11b-expressing professional antigen-presenting cells such as myeloid dendritic cells. This allows delivery of CD8+ T-cell epitopes to the major histocompatibility complex (MHC) class I presentation pathway. Recombinant detoxified ACT containing an epitope of the Plasmodium berghei circumsporozoite protein (CSP), indeed, induced a specific CD8+ T-cell response in immunized mice after a single application, as detected by MHC multimer staining and gamma interferon (IFN-gamma) ELISPOT assay. This CSP-specific response could be significantly enhanced by prime-boost immunization with recombinant ACT in combination with anti-CTLA-4 during the boost immunization. This increased response was accompanied by complete protection in a number of mice after a challenge with P. berghei sporozoites. Transient blockade of CTLA-4 may overcome negative regulation and hence provide a strategy to enhance the efficacy of a vaccine by amplifying the number of responding T cells.