Heart rate variability as a predictor of successful catheter-guided pulmonary vein isolation for atrial fibrillation.

BACKGROUND: This retrospective observational study investigated the relationship between heart rate variability (HRV) and atrial fibrillation (AF) recurrence after pulmonary vein isolation (PVI) by cryoballoon or radiofrequency ablation (RF). METHODS: We enrolled 497 patients who underwent PVI using first-generation cryoballoon (CB1), second-generation cryoballoon (CB2), or RF. We analyzed HRV as a surrogate for modulation of the intrinsic autonomic nervous system using 24­h Holter recordings 1 or 2 days after the procedure and compared the recurrence and non-recurrence group with regard to ablation methods. Furthermore, we calculated recurrence-free survival (RFS) below/over HRV cut-off values for the whole study population and separately for each ablation method. RESULTS: All except one of the five time-based HRV parameters analyzed were significantly lower in the non-recurrence group than in the recurrence group after CB2. Only a trend toward lower HRV for the non-recurrence group was found after RF and no remarkable differences were detected after CB1. The HRV parameters below their calculated cut-off were associated with a significantly higher RFS rate 2 years after CB2. This also applied to root mean sum of squared distance (rMSSD) and the percentage of adjacent NN interval differences greater than 50 ms (pNN50) after RF. No differences were found regarding CB1. Concerning rMSSD, the sensitivity, specificity, and difference in RFS increased when using cut-offs that were calculated including only CB2 patients. Multivariate cox regression analysis showed that low rMSSD values could independently predict AF recurrence after adjusting for covariates (hazard ratio: 0.50; p < 0.001). CONCLUSION: Low values of rMSSD early after a PVI could independently predict AF recurrence, especially after CB2.

Factor VII-activating protease deficiency promotes neointima formation by enhancing leukocyte accumulation.

Essentials Factor VII-activating protease (FSAP) is a plasma protease involved in vascular processes. Neointima formation was investigated after vascular injury in FSAP-/- mice. The neointimal lesion size and the accumulation of macrophages were increased in FSAP-/- mice. This was due to an increased activity of the chemokine (C-C motif) ligand 2 (CCL2). SUMMARY: Background Factor VII-activating protease (FSAP) is a multifunctional circulating plasma serine protease involved in thrombosis and vascular remodeling processes. The Marburg I single-nucleotide polymorphism (MI-SNP) in the FSAP-coding gene is characterized by low proteolytic activity, and is associated with increased rates of stroke and carotid stenosis in humans. Objectives To determine whether neointima formation after vascular injury is increased in FSAP-/- mice. Methods and Results The neointimal lesion size and the proliferation of vascular smooth muscle cells (VSMCs) were significantly enhanced in FSAP-/- mice as compared with C57BL/6 control mice after wire-induced injury of the femoral artery. Accumulation of leukocytes and macrophages was increased within the lesions of FSAP-/- mice at day 3 and day 14. Quantitative zymography demonstrated enhanced activity of gelatinases/matrix metalloproteinase (MMP)-2 and MMP-9 within the neointimal lesions of FSAP-/- mice, and immunohistochemistry showed particular costaining of MMP-9 with accumulating leukocytes. Using intravital microscopy, we observed that FSAP deficiency promoted the intravascular adherence and the subsequent transmigration of leukocytes in vivo in response to chemokine ligand 2 (CCL2). CCL2 expression was increased in FSAP-/- monocytes but not in the vessel wall. There was no difference in the expression of platelet-derived growth factor (PDGF-BB). Conclusions FSAP deficiency causes an increase in CCL2 expression and CCL2-mediated infiltration of leukocytes into the injured vessel, thereby promoting SMC proliferation and migration by the activation of leukocyte-derived gelatinases. These results provide a possible explanation for the observed association of the loss-of-function MI-SNP with vascular proliferative diseases.

Quantitative CT imaging of the spatio-temporal distribution patterns of vasa vasorum in aortas of apoE-/-/LDL-/- double knockout mice.

OBJECTIVE: To investigate the distribution of vasa vasorum (VV) relative to advanced atherosclerotic lesions (calcified, fibrotic or hemorrhaged) along the aortic wall of apoE-/-/LDL-/- mice at the age of 25 and 80 weeks using high-resolution nano-CT. METHODS: Aortas from male apoE-/-/LDL-/- mice at the age of 25 weeks (n=4) and 80 weeks (n=7) were infused in situ with contrast agent and harvested for scanning with nano-CT. The spatial distribution of vasa vasorum [number and area/cross-section (mm2)] was compared to aortic luminal cross-sectional area and plaque cross-sectional area in the ascending aorta, aortic arch and descending aorta. Results were complemented with co-localized histology. RESULTS: The number and total luminal cross-sectional area of VV showed a significant decrease in the ascending aorta and aortic arch from 25 to 80 weeks but not in the descending aorta. The number and cross-sectional area of VV showed significant local differences depending on whether it was near a fibrotic, and hemorrhaged or calcified plaque in animals at the age of 80 weeks. Area of VV progressively increased along the aorta from least in the ascending aorta