Mechanical atherothrombectomy improves endothelial function through plaque burden reduction in PAD.

Background: Endothelial dysfunction defines outcomes and serves as a surrogate parameter for the progression of cardiovascular disease. For symptomatic peripheral artery disease (PAD) endovascular treatment is the primary revascularization strategy, which affects endothelial function. Interventional mechanical atherothrombectomy (MATH) provides advantages when treating complex atherosclerotic and thrombotic lesions. We now aimed to determine the impact and mechanisms of MATH on endothelial function. Patients and methods: Endothelial function was determined using flow-mediated dilation (FMD) before and after lower limb intervention with a six-month follow-up in the target and control vessel in 15 PAD MATH+DCB treated patients and compared to 15 non-Math controls. In a further cohort of 20 patients the impact of MATH and DCB on vascular structure and virtual histology was assessed through intravascular ultrasound (IVUS) and compared to DCB treatment alone. Results: Improved endothelial function after 6 months was observed in both groups for the target and nontarget vessel. When comparing the changes from baseline endothelial function, treatment with MATH+DCB was superior to DCB treatment in the target vessel. IVUS revealed a greater improvement in luminal area and plaque burden reduction after MATH treatment. Virtual histology disclosed MATH-associated changes in plaque composition evidenced by alterations in fibrous volume and reductions in superficial calcium. Conclusions: We demonstrate an improved endothelial function after MATH treatment as compared to DCB treatment. The improved vessel function is evidenced by MATH-related plaque burden reduction, improved luminal gain and a decrease in superficial calcification. Clinicaltrials.gov: NCT04092972.

The impact of percutaneous peripheral interventions on endothelial function.

Background: Treatment of symptomatic peripheral artery disease (PAD) through endovascular interventions is the primary revascularization strategy. Interventions restore perfusion but may cause severe injury to the vascular endothelium, which regulates vascular tone. Endothelial dysfunction is involved in the progression of cardiovascular disease, with higher incidences of vascular events. We aimed to determine the impact of percutaneous interventions on change in endothelial function. Patients and methods: Endothelial function was determined using flow-mediated dilation (FMD) before, the day after lower limb intervention with paclitaxel-coated balloons or stent guided interventions and after a six-month follow-up in the target limb, control limb and the systemic circulation in 42 PAD patients aged 70.2±9 years and 66% men. Additionally, macro- and microvascular function were assessed. Results: In PAD patients aged 70.2±9 years and 66% men, we observed an immediate enhancement of macro-, microvascular and endothelial function after endovascular treatment (FMD of superficial femoral artery (SFA) 3.7±0.2% to 4.1±0.1%, n=42, p=0.02), a sustained long-term improvement after 6-months (FMD SFA 3.7±0.2% to 4.2±0.1%, n=42, p=0.01), and moreover an improved systemic endothelial function (FMD brachial artery 4.3±0.1% to 4.7±0.2, n=42, p=0.01) following peripheral interventions. Subgroup analysis however revealed that following paclitaxel-based percutaneous intervention, the paclitaxel dosage applied was inversely related to the chronic improvement in local endothelial function (r=-0.6, n=22, p=0.005) without evidence for systemic effects (r=-0.25, p=0.27). Conclusions: We demonstrate an improved local and systemic endothelial function after treatment of atherosclerotic peripheral disease with a distinguished response after endovascular intervention with higher dosage of applied paclitaxel restraining the benefits. Further studies have to determine the optimal interventional strategy with respect to different treatment modalities to maintain vessel functions.