While risk scores are invaluable tools for adapted preventive strategies, a significant gap exists between predicted and actual event rates. Additional tools to further stratify the risk of patients at an individual level are biomarkers. A surrogate endpoint is a biomarker that is intended as a substitute for a clinical endpoint. In order to be considered as a surrogate endpoint of cardiovascular events, a biomarker should satisfy several criteria, such as proof of concept, prospective validation, incremental value, clinical utility, clinical outcomes, cost-effectiveness, ease of use, methodological consensus, and reference values. We scrutinized the role of peripheral (i.e. not related to coronary circulation) noninvasive vascular biomarkers for primary and secondary cardiovascular disease prevention. Most of the biomarkers examined fit within the concept of early vascular aging. Biomarkers that fulfill most of the criteria and, therefore, are close to being considered a clinical surrogate endpoint are carotid ultrasonography, ankle-brachial index and carotid-femoral pulse wave velocity; biomarkers that fulfill some, but not all of the criteria are brachial ankle pulse wave velocity, central haemodynamics/wave reflections and C-reactive protein; biomarkers that do no not at present fulfill essential criteria are flow-mediated dilation, endothelial peripheral arterial tonometry, oxidized LDL and dysfunctional HDL. Nevertheless, it is still unclear whether a specific vascular biomarker is overly superior. A prospective study in which all vascular biomarkers are measured is still lacking. In selected cases, the combined assessment of more than one biomarker may be required.

Purpose: To evaluate the safety and feasibility of treating calcified infrapopliteal stenoses using an intravascular lithotripsy (IVL) system. Methods: The Disrupt BTK study was a prospective, nonrandomized, multicenter, feasibility, and safety trial that enrolled 20 patients (mean age 79.0±9.6 years; 14 men) at 3 participating sites (ClinicalTrials.gov identifier NCT02911623). Fifteen patients had Rutherford category 5 ischemia, and all patients had moderate to severe below-the-knee arterial calcification. Patients were treated with the Shockwave Medical Peripheral IVL System and followed for 30 days. The primary safety endpoint was a composite of major adverse events through 30 days defined as death, myocardial infarction, need for emergency surgical revascularization of the target limb, or amputation of the target limb. The primary effectiveness outcome was acute reduction in the percent diameter stenosis. Results: IVL catheter delivery was successful in 19 patients. The composite of major adverse events at 30 days was 0%. The acute reduction in percent diameter stenosis of target lesions was 46.5%. All patients achieved residual diameter stenosis ≤50%. Vascular complications were minimal with only 1 type B dissection reported and 2 stents placed. None of the subjects experienced thrombus formation, abrupt closure, distal embolization, or perforation. There were no device-related complications. Conclusion: The early results of this pilot study demonstrated that calcified, stenotic infrapopliteal arteries can be safely and successfully treated with intravascular lithotripsy.

This study sought to evaluate the safety and effectiveness of a paclitaxel-coated drug-coated balloon (DCB) for the treatment of patients with de novo in-stent restenosis (ISR). Treatment of patients with ISR remains a challenge. Current strategies are plagued by high rates of recurrent restenosis and need for reintervention. The best intervention for ISR remains to be elucidated. The IN.PACT Global study is an independently adjudicated multicenter, prospective, single-arm study that enrolled 1,535 subjects with symptomatic atherosclerotic disease of the superficial femoral and/or popliteal arteries, including de novo ISR lesions. Patients enrolled in the pre-specified ISR imaging cohort were evaluated for vessel patency and reintervention within the 12-month follow-up period. A total of 131 subjects with 149 ISR lesions were included for analysis. The mean age of the cohort was 67.8 years. Mean lesion length was 17.17 ± 10.47 cm, including 34.0% total occlusions and 59.1% calcified lesions. The 12-month Kaplan-Meier estimate of primary patency was 88.7%. The rate of clinically driven target lesion revascularization (CD TLR) at 12 months was 7.3%. The primary safety outcome, a composite of freedom from device- and procedure-related mortality through 30 days and freedom from major target limb amputation and CD TLR within 12 months, was 92.7%. There were no major target limb amputations, no deaths, and a low (0.8%) thrombosis rate. Results from the ISR imaging cohort demonstrate high patency and a low rate of CD TLR at 12 months. These data confirm the safety and effectiveness of the IN.PACT Admiral DCB (Medtronic, Dublin, Ireland) in complex femoropopliteal lesions, including this challenging subset.