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Background LAA occlusion has a similar stroke prevention efficacy compared to anticoagulation treatment for non-valvular atrial fibrillation. Objective The objective of this study was to assess the feasibility and safety of a modified Occlutech® left atrial appendage (LAA) closure device in a canine model. Methods The device was implanted in 10 dogs (33±1kg) using fluoroscopy and transesophageal echocardiography (TEE) guidance. The modified Occlutech® LAA occlusion device was compared with the current version, the Watchman device, and the Amplazter cardiac plug (ACP). LAA occlusion and anchoring to the LAA were evaluated. All dogs were assessed using angiography, TEE, and a gross anatomy examination. Results The 10 LAA occlusion devices were to be implanted into 10 dogs (5 modified Occlutech devices, 3 current version of Occlutech devices, 1 Watchman, and 1 ACP). LAA implantation was not performed in one dog due to transeptal puncture failure. The three current version of Occlutech devices were embolized immediately after implantation, so three modified devices of the same size were implanted securely without embolization. The mean implant size was 20.1±2.0mm. The devices chosen were a mean of 23.3±10.6% larger than the measured landing zone diameters. Post-implant angiography and TEE revealed well-positioned devices without pericardial effusion or impingement on surrounding structures. Conclusions The results of this acute animal study suggested that a modified Occlutech® LAA occlusion device was feasible and had greater anchoring performance in canines. Additional large clinical studies are needed to evaluate safety and efficacy.

Aim: The sodium-glucose cotransporter 2 inhibitor (SGLT-2i) suggested a possible anti-atherosclerotic and cardioprotective effects beyond glucose lowering effect. However, further study is needed to prove underlying mechanisms of improve on cardiovascular outcomes by SGLT-2i. Therefore, we investigated possible underlying anti-atherosclerotic effect of SGLT-2i ‘Dapagliflozin’ with diabetic rabbit model by inducing atherosclerosis. Methods: Rabbit divided into two groups (each group/n=10); DA: Diabetic atherosclerosis, DAD: Diabetic atherosclerosis + Dapagliflozin. Dapagliflozin was given for a total of 8 weeks. Atherosclerotic plaques were induced with a high cholesterol (HC) diet and balloon inflation. In vivo intravascular imaging and histological assessment was performed. Results: From the histologic evaluation, atheromatous plaque and lipid accumulation were significantly less developed in the Diabetic atherosclerosis + Dapagliflozin group compared to the Diabetic atherosclerosis group. Significantly less macrophage infiltration and inflammatory proteins expression level was observed in the Diabetic atherosclerosis + Dapagliflozin group. The mRNA and protein level of pro-inflammatory markers such as HMGB1, TNF-α, iNOS, and RAGE were significantly lower in the Diabetic atherosclerosis + Dapagliflozin group. The polarization of M1 macrophages was also significantly lower in the Dapagliflozin treated group. The fibronectin and type IV collagen were less observed in the glomerulus of kidney in the Dapagliflozin treated group. The lipid droplet area and size in the liver of Dapagliflozin treated group was smaller and fewer than those in the non-treated group. Conclusion: These results suggest that dapagliflozin may prevent an acceleration atherosclerosis by reducing a vascular inflammation and modifying the macrophage polarization in diabetic animal model. This preliminary clinical observation demonstrates the therapeutic potential of dapagliflozin in diabetic patients with cardiovascular disease.

In-stent restenosis (ISR) often occurs after applying drug eluting stents to the blood vessels suffering from atherosclerosis or thrombosis. For treatment of ISR, drug eluting balloons (DEB) have been developed to deliver anti-proliferative drugs to the lesions with ISR. However, there are still limitations of DEB such as low drug delivery efficiency and drug loss to blood flow. Although most researches have focused on alteration of drug formulation for more efficient drug delivery, there are few studies that have attempted to understand and utilize the contact modality of DEB drug delivery. Here, we developed a linear micro-patterned DEB (LMDEB) that applied higher contact pressure to enhance drug stamping to vascular tissue. Ex vivo and in vivo studies confirmed that higher contact pressure from micro-patterns increased the amount of drug delivered to the deeper regions of vessel. Finite element method simulation also showed significant increase of contact pressure between endothelium and micro-patterns. Quantitative analysis by high performance liquid chromatography indicated that LMDEBs delivered 2.3 times higher amount of drug to vascular tissue in vivo than conventional DEBs. Finally, efficacy studies using both atherosclerotic and ISR models demonstrated superior patency of diseased vessels treated with LMDEB compared to those treated with DEB.

Objective: Both statin and angiotensin receptor blocker (ARB) are well known to prevent the progression of atherosclerosis. However, the additive effects of anti-atherosclerosis at early period are not fully investigated. Therefore, we tried to investigate whether an anti-atherosclerotic effect of statin and ARB could be synergistic and clarify its mechanisms. Methods: Atherosclerotic plaques were developed at 23 rabbits’ iliac arteries with a high cholesterol (HC) diet and balloon inflation. We applied with 5 different treatment for 4 weeks; group 1 [n=5, HC diet]; group 2 [n=3, a regular chow diet]; group 3 [n=5, HC diet and rosuvastatin (R, 10 mg/kg)]; and group 4 [n=5, HC diet and olmesartan (O, 20 mg/kg)]; group 5 [n=5, HC diet and R + O]. End of the period, optical coherence tomography (OCT) was performed to detect the plaque characteristics and all tissues were harvested for histological evaluation. Results: Histological analysis demonstrated that atherosclerotic plaque lesions (Intima/plaque ratio, %) were decreased in the combination group compared to the statin (p=0.001) or ARB group (p=0.17). The macrophage infiltration of RAM11 staining was not significantly different between combination and each treatment group (mean±SEM=31.8±4.8% (R+O) vs. 38.1±6.53% (R), p=0.35 or 35.1±2.9% (O), p=0.62). Relative area of macrophage M1 polarization (iNOS staining) was significantly lower in the combination group compared to ARB group (3.2±0.5% (R+O) vs. 4.6 ±0.4% (R), p=0.09 or 5.2±1.0% (O), p=0.03). M2 macrophage polarization (Arg-1 staining) revealed increase in the combination group compared to each treatment group (17.7±3.0% (R+O) vs. 7.9±0.7% (R), p=0.002 or 11.9±2.8% (O), p=0.05) Conclusion: The combination of statin and ARB appeared more beneficial effects to reduce plaque formation, which may be associated with modulation of macrophage subtype in early period.