Thromboembolism after electrical isolation of the left atrial appendage: a new indication for interventional closure?

AIMS: Left atrial appendage electrical isolation (LAAI) may improve the rhythm outcome in selected patients with atrial fibrillation (AF). Controversy exists if LAAI is associated with an increased rate of thromboembolic complications. We sought to assess the feasibility, efficacy, and safety of interventional left atrial appendage closure (LAAC) in comparison to oral anticoagulation (OAC) after electrical LAAI. METHODS AND RESULTS: Weeks after index LAAI using the cryoballoon or a linear maze like ablation strategy patients' left atrial appendage was invasively remapped. In case of persistent LAAI, LAAC was performed. Patients who refused invasive remapping continued OAC. The primary endpoint was composed of any stroke or systemic embolism (SE) and the occurrence of intracardiac thrombus. Secondary endpoints included stroke/SE, major bleeding, and all-cause death. Of 166 patients (51% female; mean age 70 ± 8 years; mean CHAD2S2VASc score 3.4 ± 1.8) after LAAI, 94 patients received LAAC (LAAC group) and 72 continued OAC (no LAAC). After LAAC, 83% of patients received dual antiplatelet therapy for 6 weeks and aspirin thereafter. During a mean follow-up of 778 ± 630 days, 5 and 11 primary endpoint events were observed in the LAAC and no LAAC group, respectively [hazard ratio (HR) 0.27, 95% confidence interval (CI) 0.10-0.75; P = 0.010]. The calculated annual thromboembolic event rates were 6.9% (no LAAC) and 2.3% (LAAC), respectively. Left atrial appendage closure significantly reduced the incidence of stroke and SE (HR 0.31, CI 0.1-0.98; P = 0.04). CONCLUSION: After electrical LAAI for rhythm control in AF patients, interventional LAAC was associated with fewer thromboembolic complications when compared with OAC.

Sugar-based collagen membrane cross-linking increases barrier capacity of membranes.

OBJECTIVES: This study examines the permeability and barrier capacity of a sugar cross-linked resorbable collagen membrane ex vivo and in vivo. MATERIALS AND METHODS: In an ex vivo study, injectable platelet-rich fibrin (i-PRF), a peripheral blood-derived human leukocyte-and-platelet-rich plasma was used to analyze membrane permeability. in vivo subcutaneous implantation in Wistar rats (n = 4 per time point and group) was used to investigate the barrier capacity of the membrane. The induced in vivo cellular reaction was evaluated at 3, 15, and 30 days and compared to sham OP (control) without biomaterial using histological, immunohistochemical, and histomorphometric methods. RESULTS: Ex vivo, the membrane was impenetrable to leukocytes, platelets, and fibrin from peripheral human blood concentrate (PRF). In vivo, the membrane maintained its structure and remained impervious to cells, connective tissue, and vessels over 30 days. CD-68-positive cell (macrophage) numbers significantly decreased from 3 to 15 days, while from day 15 onwards, the number of multinucleated giant cells (MNGCs) increased significantly. Correspondingly, a rise in implantation bed vascularization from 15 to 30 days was observed. However, no signs of degradation or material breakdown were observed at any time point. CONCLUSION: Ex vivo and in vivo results showed material impermeability to cellular infiltration of human and murine cells, which highlights the membrane capacity to serve as a barrier over 30 days. However, whether the induced MNGCs will lead to material degradation or encapsulation over the long term requires further investigation. CLINICAL RELEVANCE: The data presented are of great clinical interest, as they contribute to the ongoing discussion concerning to what extent an implanted material should be integrated versus serving only as a barrier membrane.

Reduction of the relative centrifugal force influences cell number and growth factor release within injectable PRF-based matrices.

Platelet rich fibrin (PRF) is a blood concentrate system obtained by centrifugation of peripheral blood. First PRF matrices exhibited solid fibrin scaffold, more recently liquid PRF-based matrix was developed by reducing the relative centrifugation force and time. The aim of this study was to systematically evaluate the influence of RCF (relative centrifugal force) on cell types and growth factor release within injectable PRF- in the range of 60-966 g using consistent centrifugation time. Numbers of cells was analyzed using automated cell counting (platelets, leukocytes, neutrophils, lymphocytes and monocytes) and histomorphometrically (CD 61, CD- 45, CD-15+, CD-68+, CD-3+ and CD-20). ELISA was utilized to quantify the concentration of growth factors and cytokines including PDGF-BB, TGF-ß1, EGF, VEGF and MMP-9. Leukocytes, neutrophils, monocytes and lymphocytes had significantly higher total cell numbers using lower RCF. Whereas, platelets in the low and medium RCF ranges both demonstrated significantly higher values when compared to the high RCF group. Histomorphometrical analysis showed a significantly high number of CD61+, CD-45+ and CD-15+ cells in the low RCF group whereas CD-68+, CD-3+ and CD-20+ demonstrated no statistically significant differences between all groups. Total growth factor release of PDGF-BB, TGF-ß1 and EGF had similar values using low and medium RCF, which were both significantly higher than those in the high RCF group. VEGF and MMP-9 were significantly higher in the low RCF group compared to high RCF. These findings support the LSCC (low speed centrifugation concept), which confirms that improved PRF-based matrices may be generated through RCF reduction. The enhanced regenerative potential of PRF-based matrices makes them a potential source to serve as a natural drug delivery system. However, further pre-clinical and clinical studies are required to evaluate the regeneration capacity of this system.