No abstract

WHAT THIS PAPER ADDSThe current strategies to reduce intimal hyperplasia (IH) rely principally on local drug delivery, in an endovascular approach. The oral angiotensin converting enzyme inhibitor (ACEi) zofenopril has additional effects to other non-sulfyhydrated ACEi to prevent intimal hyperplasia and re-stenosis. Given the number of patients treated with ACEi worldwide, these findings call for further prospective clinical trials to test the benefits of sulfhydrated ACEi over classic ACEi for the prevention of re-stenosis in hypertensive patients.Objective: Hypertension is a major risk factor for intimal hyperplasia (IH) and re-stenosis following vascular and endovascular interventions. Preclinical studies suggest that hydrogen sulphide (H 2 S), an endogenous gasotransmitter, limits re-stenosis. While there is no clinically available pure H 2 S releasing compound, the sulfhydryl containing angiotensin converting enzyme inhibitor zofenopril is a source of H 2 S. Here, it was hypothesised that zofenopril, due to H 2 S release, would be superior to other non-sulfhydryl containing angiotensin converting enzyme inhibitors (ACEi) in reducing intimal hyperplasia. Methods: Spontaneously hypertensive male Cx40 deleted mice (Cx40 e/e ) or wild type (WT) littermates were randomly treated with enalapril 20 mg or zofenopril 30 mg. Discarded human vein segments and primary human smooth muscle cells (SMCs) were treated with the active compound enalaprilat or zofenoprilat. IH was evaluated in mice 28 days after focal carotid artery stenosis surgery and in human vein segments cultured for seven days ex vivo. Human primary smooth muscle cell (SMC) proliferation and migration were studied in vitro.Results: Compared with control animals (intima/media thickness 2.3 AE 0.33 mm), enalapril reduced IH in Cx40 e/e hypertensive mice by 30% (1.7 AE 0.35 mm; p ¼ .037), while zofenopril abrogated IH (0.4 AE 0.16 mm; p < .002 vs. control and p > .99 vs. sham operated Cx40 e/e mice). In WT normotensive mice, enalapril had no effect (0.9665 AE 0.2 mm in control vs. 1.140 AE 0.27 mm; p > .99), while zofenopril also abrogated IH (0.1623 AE 0.07 mm; p < .008 vs. control and p > .99 vs. sham operated WT mice). Zofenoprilat, but not enalaprilat, also prevented IH in human vein segments ex vivo. The effect of zofenopril on carotid and SMCs correlated with reduced SMC proliferation and migration. Zofenoprilat inhibited the mitogen activated protein kinase and mammalian target of rapamycin pathways in SMCs and human vein segments. Conclusion: Zofenopril provides extra beneficial effects compared with non-sulfhydryl ACEi in reducing SMC proliferation and re-stenosis, even in normotensive animals. These findings may hold broad clinical implications for patients suffering from vascular occlusive diseases and hypertension.

No abstract

WHAT THIS STUDY ADDS Recent long-term results of arterial allografts used for distal bypasses in the setting of chronic ischaemia are lacking. This study confirms that the use of modern cryopreserved arterial allografts allows for an excellent limb salvage rate, at the cost of a relatively high re-intervention rate. This material should be considered as a valuable alternative to prosthetic material when no venous material is available. Objective/Background: In critical limb ischaemia (CLI), current guidelines recommend revascularisation whenever possible, preferentially through endovascular means. However, in the case of long occlusions or failed endovascular attempts, distal bypasses still have a place. Single segment great saphenous vein (GSV), which provides the best conduit, is often not available and currently there is no consensus about the best alternative graft. Methods: From January 2006 to December 2015, 42 cryopreserved arterial allografts were used for a distal bypass. Autologous GSVs or alternative autologous conduits were unavailable for all patients. The patients were observed for survival, limb salvage, and allograft patency. The results were analysed with KaplaneMeier graphs. Results: Estimates of secondary patency at one, two and five years were 81%, 73%, and 57%, respectively. Estimates of primary patency rates at one, two and five years were 60%, 56%, and 26%, respectively. Estimates of limb salvage rates at one, two and five years were 89%, 89%, and 82%, respectively. Estimates of survival rates at one, two and five years were 92%, 76% and 34%, respectively. At 30 days, major amputations and major adverse cardiac events were one and zero, respectively. Six major amputations occurred during the long-term follow up. Conclusion: Despite a low primary patency rate at two years, the secondary patency of arterial allografts is acceptable for distal bypasses. This suggests that cryopreserved arterial allografts are a suitable alternative for limb saving distal bypasses in the absence of venous conduits, improving limb salvage rates and, possibly, quality of life.

No abstract

No abstract

Background The COVID-19 pandemic has led to widespread postponement and cancelation of elective vascular surgeries in Switzerland. The consequences of these decisions are poorly understood. Patients and methods In this observational, retrospective, single-center cohort study, we describe the impact of COVID-19 pandemic containment strategies on patients with lower extremity peripheral arterial disease (PAD) referred during the period March 11 th -May 11 th , 2020, compared to the same time frames in 2018-2019. Patients admitted for acute limb ischemia (ALI) or chronic PAD and undergoing urgent or elective vascular surgery or primary amputation were included. Patients’ characteristics, indications for admission, and surgical features were analyzed. The occurrence of 30-day outcomes was assessed, including length of stay, rates of major adverse cardiovascular events (MACE) and major adverse limb events (MALE), and procedural and hemodynamic success. Results Overall, 166 patients were included. Fewer subjects per 10-day period were operated in 2020 compared to 2018-2019 (6.7 vs. 10.5, respectively; p < 0.001). The former had higher rates of chronic obstructive pulmonary disease (COPD) (25% vs. 11.1%; p = 0.029), and ASA score (3.13 vs. 2.90; p = 0.015). The percentage of patients with ALI in 2020 was about double that of the same period in 2018-2019 (47.5% vs. 24.6%; p = 0.006). Overall, the types of surgery were similar between 2020 and 2018-2019, while palliative care and primary amputations occurred only in 2020 (5 out 40 cases). The rate of post-operative MACE was significantly higher in 2020 (10% vs. 2.4%; p = 0.037). Conclusions During the first state of emergency for COVID-19 pandemic in 2020, less regular medical follow-up and hindered hospital access could have resulted in more acute and advanced clinical presentations of patients with PAD undergoing surgery. Guidelines are needed to provide appropriate care to this vulnerable population and avoid a large-scale disaster.

No abstract