Cycle Length Evaluation in Persistent Atrial Fibrillation Using Kernel Density Estimation to Identify Transient and Stable Rapid Atrial Activity.

PURPOSE: Left atrial (LA) rapid AF activity has been shown to co-localise with areas of successful atrial fibrillation termination by catheter ablation. We describe a technique that identifies rapid and regular activity. METHODS: Eight-second AF electrograms were recorded from LA regions during ablation for psAF. Local activation was annotated manually on bipolar signals and where these were of poor quality, we inspected unipolar signals. Dominant cycle length (DCL) was calculated from annotation pairs representing a single activation interval, using a probability density function (PDF) with kernel density estimation. Cumulative annotation duration compared to total segment length defined electrogram quality. DCL results were compared to dominant frequency (DF) and averaging. RESULTS: In total 507 8 s AF segments were analysed from 7 patients. Spearman's correlation coefficient was 0.758 between independent annotators (P < 0.001), 0.837-0.94 between 8 s and ≥ 4 s segments (P < 0.001), 0.541 between DCL and DF (P < 0.001), and 0.79 between DCL and averaging (P < 0.001). Poorer segment organization gave greater errors between DCL and DF. CONCLUSION: DCL identifies rapid atrial activity that may represent psAF drivers. This study uses DCL as a tool to evaluate the dynamic, patient specific properties of psAF by identifying rapid and regular activity. If automated, this technique could rapidly identify areas for ablation in psAF.

Evaluation of new Forcefield technology: reducing platelet adhesion and cell coverage of pyrolytic carbon surfaces.

INTRODUCTION: Platelet adhesion and activation are a significant source of clinical complications. Preventing foreign surface-platelet interaction may improve biocompatibility of implantable medical devices. This study evaluated efficacy of novel technique for electrically modifying surface of conductive biomaterial and attaching blood components to prevent thrombogenesis. Specifically, this new surface modification technology, Forcefield (ATS Medical, Inc, Minneapolis, Minn), was designed to prevent platelet adhesion on pyrolytic carbon. A modulated low-voltage current is directly applied to pyrolytic carbon surfaces to stimulate adherence of a layer of charged proteins from circulating blood components that is resistive to platelet deposition. METHODS: Feasibility of Forcefield technology was tested in line with cardiopulmonary bypass circuit in patients undergoing standard cardiac surgery (n = 6). Forcefield treatment was applied to segment of pyrolytic carbon with 15 minutes (n = 3) and 30 minutes (n = 3) of electrically stimulated exposure time, and resulting segments were compared with untreated pyrolytic carbon segment. Platelet adhesion confluence was then quantified by scanning electron microscopy. RESULTS: Confluence of the Forcefield-treated pyrolytic carbon segments (3.3% ± 2.2%) was significantly reduced relative to untreated pyrolytic carbon control segments (81.7% ± 24%, P < .001). There were no discernible differences in cell confluence with Forcefield-treated segments as function of exposure time (15 or 30 minutes). CONCLUSIONS: Forcefield technology may enable modification of pyrolytic carbon surfaces to prevent platelet adhesion and thrombogenesis of implanted medical devices, including heart valves, stents, catheters, and ventricular assist devices, and may eliminate the need for anticoagulant and antiplatelet therapies.

Utilization of acoustic signatures to identify HeartMate XVE device end-of-life.

BACKGROUND: As outcomes for destination therapy continue to improve, many patients are requiring left ventricular assist device (LVAD) exchange due to end-of-life of their LVAD. Current techniques to identify and diagnose device end-of-life issues usually require invasive testing or off-site filter dust analysis. In this study we assess a non-invasive technique using acoustic signals generated from the HeartMate XVE LVAD to potentially identify impending device end-of-life issues. METHODS: Nine patients were prospectively followed after implantation of the HeartMate XVE LVAD as destination therapy between May 2004 and July 2006. Acoustic signals were collected using an aquatic hydrophone system interfaced with a data acquisition system and a standard laptop computer. Data were collected at pre-set intervals. All data/acoustic signals were prospectively interpreted by a blinded independent reviewer skilled at interpreting acoustic signals. Acoustic data suggesting possible device failure were then correlated with clinical findings and LVAD examination at the time of device removal. RESULTS: All patients survived long enough to develop signs of impending device end-of-life. Four of 9 (44%) patients developed inflow valve incompetence, 4 (44%) were identified as having significant bearing wear, and 1 (12%) had both. All acoustically identified device issues were confirmed by standard clinical examinations and testing (echocardiography, angiography, laboratory tests and filter dust analysis). The acoustic findings were subsequently confirmed at time of device exchange. All patients ultimately had their device successfully exchanged and have continued to live with their new apparatus. CONCLUSIONS: Acoustic signal monitoring can successfully identify HeartMate XVE device end-of-life. This new method provides a low-cost, reproducible, non-invasive technique that may be used to identify possible impending device failure.

Mouse lysozyme-M knockout mice reveal how the self-determinant hierarchy shapes the T cell repertoire against this circulating self antigen in wild-type mice.

We have studied T cell tolerance to defined determinants within ML-M using wild-type (WT; ML-M(+/+)) and LysMcre (ML-M(-/-)) C3H (H-2(k)) mice to determine the relative contribution of ML-M-derived epitopes vs those from other self Ags in selection of the ML-M-specific T cell repertoire. ML-M was totally nonimmunogenic in WT mice, but was rendered immunogenic in LysMcre mice. Most of the response to ML-M in LysMcre mice was directed to the immunodominant determinant region 105-119. This determinant is spontaneously displayed (without adding exogenous ML-M) by macrophages of WT, but not LysMcre, mice and is stimulatory for peptide 105-119 (p105-119)-primed T cells. Moreover, neonatal tolerization of LysMcre mice with p105-119 or ML-M abrogated the T cell response to subsequent challenge with ML-M or p105-119. Furthermore, p95-109 and p110-125 of ML-M were immunogenic in LysMcre mice, but not in WT mice, thereby representing subdominant, tolerance-inducing epitopes of ML-M. As expected, the T cell repertoire to cryptic ML determinants in WT mice was also intact in LysMcre mice. Furthermore, the pattern of response to the related homologue of ML-M, hen eggwhite lysozyme, was similar in these two groups of mice. Thus, several codominant T cell determinants within ML-M contribute significantly to tolerance induction, and the anti-cryptic T cell repertoire to ML-M was positively selected on non-ML-M self ligands. These results reveal that the induction of self tolerance to a multideterminant protein follows the quantitative hierarchy of self-determinant expression and are of relevance in understanding the pathogenesis of autoimmunity.