Initial experience of the High-Density Grid catheter in patients undergoing catheter ablation for atrial fibrillation

Purpose

A significant proportion of patients undergoing catheter ablation for atrial fibrillation (AF) experience arrhythmia recurrence. This is mostly due to pulmonary vein reconnection (PVR). Whether mapping using High-Density Wave (HDW) technology is superior to standard bipolar (SB) configuration at detecting PVR is unknown. We aimed to evaluate the efficacy of HDW technology compared to SB mapping in identifying PVR.

Methods

High-Density (HD) multipolar Grid catheters were used to create left atrial geometries and voltage maps in 36 patients undergoing catheter ablation for AF (either due to recurrence of an atrial arrhythmia from previous AF ablation or de novo AF ablation). Nineteen SB maps were also created and compared. Ablation was performed until pulmonary vein isolation was achieved.

Results

Median time of mapping with HDW was 22.3 [IQR: 8.2] min. The number of points collected with HDW (13299.6±1362.8 vs 6952.8±841.9, p<0.001) and used (2337.3±158.0 vs 1727.5±163.8, p<0.001) was significantly higher compared to SB. Moreover, HDW was able to identify more sleeves (16 for right and 8 for left veins), where these were confirmed electrically silent by SB, with significantly increased PVR sleeve size as identified by HDW (p<0.001 for both right and left veins). Importantly, with the use of HDW, the ablation strategy changed in 23 patients (64% of targeted veins) with a significantly increased number of lesions required as compared to SB for right (p=0.005) and left veins (p=0.003).

Conclusion

HDW technology is superior to SB in detecting pulmonary vein reconnections. This could potentially result into a significant change in ablation strategy and possibly to increased success rate following pulmonary vein isolation.

     

Impact of multiple cardiovascular risk factors on femoral artery intima-media thickness in asymptomatic young adults (the Bogalusa Heart Study)

Femoral artery intima-media thickness (IMT), like carotid IMT, is a surrogate indicator of atherosclerotic coronary and peripheral vascular diseases in middle-aged and older adults. Although risk factors for coronary artery disease are also associated with increased IMT, especially as measured in carotid arteries, there is a paucity of information with respect to the femoral artery in this regard in the asymptomatic, younger adult population. This study examined the impact of multiple risk factors on the common femoral artery IMT as measured by B-mode ultrasonography in 1,080 black and white subjects aged 24 to 43 years (71% white and 43% men) enrolled in the Bogalusa Heart Study. Femoral IMT showed gender difference (men more than women, p = 0.001), but no racial difference. In a multivariate model, systolic blood pressure, age, male gender, cigarette smoking, and total cholesterol/high-density lipoprotein cholesterol ratios related independently, in that order, to IMT. Mean IMT increased with an increasing number of risk factors defined as values above the age-, race-, and gender-specific 75th percentile of systolic blood pressure, waist circumference, total cholesterol/high-density lipoprotein cholesterol ratio, and insulin along with smoking status (p for trend = 0.003), with respective mean IMT values of 0.66, 0.69, 0.73, and 0.79 mm for 0, 1 to 2, 3, and 4 to 5 risk factors. The odds ratio for patients with >/=3 risk factors versus no risk factors having IMT in the top fifth percentile was 4.7 (p = 0.01). The observed adverse trend of increasing femoral IMT with an increasing number of risk factors in free-living, asymptomatic young subjects underscores the need for multiple risk factors profiling in early life. Further, ultrasonography of the femoral artery in conjunction with multiple risk factor profiling can be helpful in risk stratification.     

Plasma renin activity and insulin resistance in African American and white children: the Bogalusa Heart Study

Recent studies have suggested that the renin-angiotensin system is a feature of the insulin resistance syndrome. However, whether such a relationship occurs in childhood and in both African Americans and whites is not clear. We examined this issue in a sample of 264 African American and white children aged 7 to 16 years who participated in a cross-sectional survey of the Bogalusa Heart Study (n = 3,524). Children were selected using a stratified random sampling procedure based on race-, age-, and sex-specific percentiles of diastolic blood pressure. Whites had higher plasma renin activity than African Americans (7.1 +/- 3.6 ng/mL/h v 5.3 +/- 3.5 ng/mL/h, P < .01). Renin activity correlated with blood pressure (BP) (r = 0.21, P < .05) and insulin resistance index defined by post-glucose 1-h insulin X 1-h glucose (r = 0.19, P < .05) only in white children. Other components of insulin resistance syndrome (percent body fat, systolic blood pressure, high-density lipoprotein cholesterol, and triglycerides) showed no relation to renin in both races using univariate analyses. The distribution of insulin resistance index and renin activity among children with elevated BP (above 90th percentile) showed that the percentage of children with both high insulin resistance index and renin values was significantly greater in whites than in African Americans (45.6% v 23.3%, P < .05). A multivariate factor analysis of risk variables of insulin resistance syndrome resulted in clusters of BP/adiposity (factor 1), lipids/adiposity (factor 2), and insulin resistance/renin/adiposity (factor 3) in white children, with adiposity linking the three factors. However, a different pattern emerged in African American children for factor 2 and factor 3, and renin was not part of the cluster in any of the three factors. These observations suggest that renin may be a component of insulin resistance syndrome detectable in early life only in whites.     

Improved survival in steroid-refractory acute graft versus host disease after non-myeloablative allogeneic transplantation using a daclizumab-based strategy with comprehensive infection prophylaxis

Approximately 15% of patients undergoing non-myeloablative allogeneic haematopoietical cell transplantation (NMHCT) develop steroid-refractory acute-graft versus host disease (aGVHD), a usually fatal complication. We encountered 18 cases of steroid-refractory aGVHD in 146 patients, undergoing NMHCT from a related human leucocyte antigen-compatible donor following cyclophosphamide/fludarabine-based conditioning. Our initial cohort of steroid-refractory aGVHD patients treated with antithymocyte globulin (ATG) and mycophenolate mofetil (regimen-1: n = 6) had high GVHD-related mortality. Therefore, we investigated an alternative strategy for subsequent patients developing this complication (regimen-2: n = 12), consisting of daclizumab (alone or combined with infliximab/ATG) and targeted broad spectrum antibacterial and aspergillus prophylaxis in conjunction with rapid tapering of steroids to minimize opportunistic infections. In a retrospective analysis, patients receiving regimen-2 were significantly more likely to have complete resolution of GVHD compared with those receiving regimen-1 [12/12 (100%) vs. 1/6 (17%); P < 0.001]. When compared with those receiving regimen-1, regimen-2 patients also had a higher probability of survival at day 100 (100% vs. 50%) and day 200 (73% vs. 17%) post-transplant, and improved overall survival (median 453 d vs. 42 d from aGVHD onset; P < 0.0001). GVHD-related mortality was 89% for regimen-1 patients vs. 17% for regimen-2 patients (P < 0.0001). These data suggest that a co-ordinated approach using immunoregulatory monoclonal antibodies, pre-emptive antimicrobial therapy and judicious steroid withdrawal can dramatically improve outcome in steroid-refractory aGVHD.     

Green fluorescent protein expression in dendritic cells enhances their immunogenicity and elicits specific cytotoxic T-cell responses in humans

OBJECTIVE: Green fluorescent protein (GFP) has been used to monitor and select cells transduced with vectors encoding other transgenes of interest. We investigated the immunogenic nature of GFP in humans and further explored whether this xenoprotein could be used as a functional adjuvant to enhance T-cell immunity to the melanoma tumor antigen MART1. METHODS: Peripheral blood lymphocytes from healthy donors were stimulated by autologous dendritic cells expressing GFP, then cloned by limiting dilution and tested for antigen specificity following coculture with GFP-expressing or GFP-negative targets. In a parallel experiment, lymphocytes from HLA A 0201+ healthy donors were stimulated with four different Melan-A/MART1(27-35) peptide-pulsed stimulators: 1) MART1 peptide-pulsed DCs, 2) MART1 peptide-pulsed DCs loaded with GFP protein, 3) MART1 peptide-pulsed GFP adenovirus-transduced DCs, and 4) MART1 peptide-pulsed null adenovirus-transduced DCs. The percentage of CD3+/CD8+ MART1 peptide-specific T cells was determined by intracellular cytokine staining for gamma-IFN. RESULTS: Multiple CD4+ and CD8+ T cell clones were expanded which secreted gamma-IFN and demonstrated high levels of cytotoxicity to GFP-expressing targets as assessed by ELISA and Cr51 release respectively. We next investigated the impact of GFP expression on DCs used to stimulate cytotoxic T cells specific for a tumor-associated peptide. The percentage of MART1- specific CD8+ T cells that were generated was higher when MART1-pulsed GFP adenovirus-transduced DCs were used as stimulators (28%) compared to MART1-pulsed DCs alone (11%, p = 0.01), MART1-pulsed null adenovirus-transduced DCs (11.7%, p = 0.02), or MART1-pulsed DCs loaded with GFP protein (12.2%). CONCLUSIONS: These findings further support GFP's immunogenicity and suggest this xenoprotein might further be used to enhance the expansion of tumor-specific T cells.     

Low density lipoprotein retention by aortic tissue. Contribution of extracellular matrix

We compared in vitro heparin binding activity and in vivo intravascular clearance and aortic uptake in rabbits of native, reductively methylated and heparin-complexed low density lipoprotein (LDL) in order to explore the extracellular matrix binding vs cellular metabolism of LDL. Reductively methylated LDL formed soluble and insoluble complexes with heparin which was comparable to native LDL. Reductive methylation of LDL produced only 30% reduction in aortic uptake vs 60% reduction in plasma clearance, reflecting the relatively smaller contribution of receptor-mediated pathway in aortic tissue vs whole animal. The intravascular clearance of native and heparin-complexed LDL remained essentially the same, indicating similarities in cellular metabolism of LDL in both cases. But the aortic uptake of the heparin bound LDL was 30% less than the native LDL, suggesting an inhibition in binding of heparin-complexed LDL to tissue proteoglycans. Saline extraction accounted for only part (53-66%) of the LDL preparations that were retained by the tissue while subsequent collagenase and elastase treatments extracted 3-5% and 17-22% of the materials respectively. These results favor the contribution of arterial extracellular matrix components to the retention of LDL.     

Serum lipoprotein profile in children from a biracial community: the Bogalusa Heart Study.

Serum lipoprotein profiles in 3182 children, ages 5-14 years, were studied in a biracial community as part of the Bogalusa Heart Study to describe the early natural history of atherosclerosis. White and black children showed similar mean levels of beta-lipoproteins. Pre-beta-lipoprotein levels, however, were significantly higher in white shildren, while significantly higher levels of alpha-lipoprotein were found in black children. Girls had generally higher levels of beta- and pre-beta-lipoprotein and lower levels of alpha-lipoprotein than boys, although the differences were not significant at each age group. With age there was little change in alpha-lipoprotein levels, a significant increase in pre-beta-lipoprotein levels and a slight but significant decrease between 11 and 14 years in beta-lipoprotein levels. The correlation of alpha-lipoprotein was negative with beta-lipoprotein and, to a greater extent, with pre-beta-lipoprotein. The above inverse relationships were significantly greater in white children than in black children, suggesting differences in lipoprotein profiles in the two groups. Lipoprotein values from a total community study are now available for comparison with the currently recommended upper normal limits for lipoproteins. Since only a very small percentage of children could be considered as hyperlipoproteinemic by those specific levels in this community, we suggest that distributions and percentiles be used to evaluate children for hyperlipoproteinemia.