Fluoroquinolone Use Preceding Visceral Artery Dissection: A Case Series.

Fluoroquinolones (FQ), commonly prescribed antibiotics, may trigger aortic and carotid dissections. We report three successive cases of visceral artery dissection: one patient with celiac trunk dissection and two with dissection of the superior mesenteric artery. These events occurred up to 4 months after 7 to 14 days of FQ treatment (2 cases of ofloxacin, 1 of norfloxacin). There was no other apparent cause of dissection. These dissections were isolated, apart from a minimal aortic dissection separate from the visceral arterial dissection in one case. A case series cannot certify the relationship between dissection and FQ, but it can be hypothesized. The association between fluoroquinolone use and higher occurrence of aneurysm and dissection remains discussed in aortic syndrome. The potential link between FQ and visceral artery dissection is even less described but should be reported in the absence of previous cases in the literature. The pathophysiological theory is the induction of overexpression of some matrix metalloproteinases and a decrease of their inhibitors, provoking a dysregulation in collagen synthesis and degradation of the extracellular matrix.

Role of the advanced nurse practitioner within the vascular team: A qualitative study of vascular physicians and nurses.

Objective: To assess the perception of Advanced Nurse Practitioners (ANP) by physicians and nurses in vascular medicine. As the status of ANP in France was recently enacted by law in 2018, we aimed to investigate physicians and nurses working with patients suffering from Peripheral Artery Disease (PAD) to gather their opinions and draw the cooperation outlines these practitioners could have with an ANP. Methods: A qualitative study based on in-depth interviews was conducted among healthcare practitioners taking care of patients with PAD: 10 physicians working either in a private practice settings or hospital settings or both, and eight nurses working within a hospital inpatients vascular unit. Verbatim responses were extracted and coded according to a continuous thematization method. Results: Three main features emerged from participants' responses. Vascular medicine has a specific organization with a significant lack of time and staff to fulfill the mission regarding patients' severity of illness. Second, the ANP is wanted to fill part of this gap. The expected benefits include a smoother care pathway and increased capacity for cardiovascular education and prevention, especially during consultations. Lastly, some clarification is required to integrate such new practitioners within vascular teams already in place. Conclusion: Advanced nurse practitioners could be the missing link in a "Vascular team" by creating a continuum in the care of patients with PAD, ensuring clinical assessment, nursing supervision, adverse event screening, and renewing drug prescriptions with the required adaptations while ensuring essential part of therapeutic education adapted to each patient.

Occurrence of Major Local Lower Limb Events in Type 2 Diabetic Patients with Lower Extremity Arterial Disease: Impact of Metformin.

BACKGROUNDS: Patients with type 2 diabetes mellitus (T2DM) are particularly at risk of developing major adverse cardiovascular events (MACE) and peripheral artery disease (PAD) due to an acceleration of the atherosclerotic process linked to hyperglycemia and inflammation with a greater risk of local complications. We aimed to identify the predictive factors for major adverse limb events (MALE) in T2DM patients with PAD to manage modifiable factors at an early stage. METHODS: This is a prospective study in which T2DM patients with PAD were included from November 2017 to May 2018 and followed over 12 months. The predictive factors for the onset of MALE, MACE, and death from all causes have been identified. RESULTS: A total of 100 patients were included; 37% of the patients developed a MALE. After multivariate analysis, metformin was associated with a decrease of MALE (odds ratio (OR) = 0.26; 95% confidence interval (CI) [0.10; 0.68]; P = 0.007), and a history of the treatment of intravenous iloprost was associated with an increased risk of MALE (OR = 5.70; 95% CI [1.31; 31.93]; P = 0.029). Regular physical activity was associated with a decreased risk of MACE (OR = 0.07; 95% CI [0; 0.44]; P = 0.021). A history of stroke and a history of venous thromboembolism were associated with an increased all-cause mortality risk with OR = 3.68; 95% CI [1.17; 11.5]; P = 0.025 and OR = 3.78; 95% CI [1.16; 12.3]; P = 0.027. CONCLUSIONS: Metformin is protective against local complications in people with diabetes with PAD and should be prescribed to diabetic patients with PAD at an early stage.

Aortic thrombosis as a dramatic vascular complication in COVID-19 disease.

OBJECTIVE: To report clinical outcomes of COVID-19 related acute aortic thrombosis (AAT). METHODS: Consecutive COVID-19 patients presenting with AAT between April 2020 and August 2021 were included retrospectively. Clinical and radiological data were prospectively collected. RESULTS: Ten patients (men, 90%; mean age, 64 ± 2 years) were included. At the time of AAT diagnosis, four patients were in intensive care unit. Median time between diagnosis of COVID-19 and AAT was 5 days [IQR 0-8.5]. Clinical presentation was acute lower limb ischaemia (n=9) and mesenteric ischaemia (n=2). Thrombus localization was the abdominal aorta (n=5), the thoracic aorta (n=2) or both (n=3), with the following embolic sites: lower limbs (n=9), renal arteries (n=3), superior mesenteric artery (n=2), splenic artery (n=1), cerebral arteries (n=1). Revascularization was performed in 9 patients, using open (n=6), endovascular (n=2) or hybrid techniques (n=1). Three patients required reinterventions. The 30-day mortality was 30%. Three major amputations were performed in two patients, resulting in a free-amputation survival rate of 50% after a median follow-up of 3,5 months [IQR 2-4.1]. CONCLUSION: AAT is a rare and devastating complication of COVID-19 disease, responsible for high mortality and amputation rates.

Bioprosthetic Total Artificial Heart Implantation Does Not Induce Chronic Inflammation.

The Aeson total artificial heart (A-TAH) has been developed for patients at risk of death from biventricular failure. We aimed to assess the inflammatory status in nine subjects implanted with the A-TAH in kinetics over one year. Laboratory assessment of leukocyte counts, inflammatory cytokines assay, and peripheral blood mononuclear cell collection before and after A-TAH implantation. Leukocyte counts were not significantly modulated according to time after A-TAH implantation (coefficient of the linear mixed effect model with 95% CI, -0.05 (-0.71 to -0.61); p = 0.44). We explored inflammatory cytokine after A-TAH and did not observe, at any time, a modified profile compared to pre-implantation values (all p -values > 0.05). Finally, we compared the distribution of circulating immune cell subpopulations identified based on sequential expression patterns for multiple clusters of differentiation. None of the population explored had significant modulation during the 12-month follow-up (all p -values > 0.05). In conclusion, using a cytokine multiplex assay combined with a flow cytometry approach, we demonstrated the absence of inflammatory signals in peripheral blood over a period of 12 months following A-TAH implantation.

Women Specific Characteristics and 1-Year Outcome Among Patients Hospitalized for Peripheral Artery Disease: A Monocentric Cohort Analysis in a Tertiary Center.

Although women have lower age-standardized cardiovascular disease incidence, prevalence, and death-related rates than men, there are also reports indicating that women with cardiovascular disease receive less care, fewer investigations, and have poorer outcomes after a coronary event. The aims of this study were to compare the characteristics of men and women hospitalized for peripheral artery disease (PAD), their cardiovascular and limb outcomes, and their 1-year mortality. The study is a prospective registry collecting data about all consecutive patients hospitalized for PAD within the vascular department of the tertiary center Georges-Pompidou European Hospital (Paris, France). Patients were required to have one of three inclusion criteria: previous revascularization of the lower limb or any lower limb artery occlusion due to an atherosclerotic vascular disease or hemodynamic evidence of PAD. Exclusion criteria were patients with lower extremity arterial occlusion due to another cause. All patients were followed-up for at least 12 months after the initial hospitalization. Among the 235 patients included, there were 61 women (26%), older than men with a median age of 75.6 and 68.3 years, respectively. Main cardiovascular risk factors and comorbidities were similar for men and women except more former or current smokers [145 (83.4%) vs. 33 (54.1%)] and more history of coronary heart disease [42 (24.1%) vs. 7 (11.5%)] in men. Most patients [138 (58.8%)] had critical limb ischemia and 97 (41.3%) had claudication, with no difference for sex. After discharge, 218 patients received an antithrombotic therapy (93.2%), 195 a lipid-lowering drug (83.3%), 185 an angiotensin converting enzyme inhibitor or angiotensin-receptor blocker (78.9%), similarly between sex. At 1-year, overall mortality, major adverse cardiovascular events, major adverse limb events did not differ with 23 (13.2%), 11 (6.3%) and 32 (18.4%) in men, and 8 (13.1%), 3 (4.9%), 15 (24.6%) in women, respectively, despite the difference in age. Overall mortality, cardiovascular outcomes, limb revascularization or amputation did not differ between men and women, 1-year after hospitalization for PAD although the latter were older, less smoker and had less coronary artery disease. Due to the small size of this cohort, larger studies and future research are needed to better understand sex-specific mechanisms in the pathophysiology and natural history of PAD.

Gonadotropins as novel active partners in vascular diseases: Insight from angiogenic properties and thrombotic potential of endothelial colony-forming cells.

BACKGROUND: The impact of estrogen and testosterone on atherosclerotic cardiovascular disease is well known, but the role of the gonadotropins follicle-stimulating hormone (FSH), luteinizing hormone (LH), and prolactin (PRL) to some extent remain less studied. OBJECTIVES: To explore the angiogenic potential of gonadotropins on endothelial colony-forming cells (ECFCs). METHODS: We examined the effects of various doses of gonadotropins on ECFCs obtained from cord blood by assessing colony number, proliferation, migration, and sprouting ability. Moreover, we studied thrombin generation in ECFCs exposed to gonadotropins by performing a thrombin generation assay. Finally, we determined the levels of circulating gonadotropins in 30 men, to exclude the effect of estrogen, with lower extremity arterial disease (LEAD), in comparison with age- and sex-matched controls. RESULTS: Exposure to FSH, LH, or PRL resulted in an increase in ECFC migration but showed no effect on proliferation or ECFC commitment from cord blood mononuclear cells. Using a three-dimensional fibrin gel assay, we showed that ECFC sprouting was significantly enhanced by gonadotropins. Exposure to FSH also increased the thrombin generation of ECFCs exposed to FSH. Finally, FSH and LH levels in men with LEAD were higher than those in controls. CONCLUSION: Gonadotropins increase ECFC-related angiogenesis and may be involved in thrombin generation in cardiovascular disease. Gonadotropins may act as biomarkers; moreover, we hypothesize that gonadotropin-blocking strategies may be a novel interesting therapeutic approach in atherosclerotic cardiovascular disease.

Elevated Circulating Stem Cells Level is Observed One Month After Implantation of Carmat Bioprosthetic Total Artificial Heart.

The Aeson® total artificial heart (A-TAH) has been developed as a total heart replacement for patients at risk of death from biventricular failure. We previously described endothelialization of the hybrid membrane inside A-TAH probably at the origin of acquired hemocompatibility. We aimed to quantify vasculogenic stem cells in peripheral blood of patients with long-term A-TAH implantation. Four male adult patients were included in this study. Peripheral blood mononuclear cells were collected before A-TAH implantation (T0) and after implantation at one month (T1), between two and five months (T2), and then between six and twelve months (T3). Supervised analysis of flow cytometry data confirmed the presence of the previously identified Lin-CD133+CD45- and Lin-CD34+ with different CD45 level intensities. Lin-CD133+CD45-, Lin-CD34+CD45- and Lin-CD34+CD45+ were not modulated after A-TAH implantation. However, we demonstrated a significant mobilization of Lin-CD34+CD45dim (p = 0.01) one month after A-TAH implantation regardless of the expression of CD133 or c-Kit. We then visualized data for the resulting clusters on a uniform manifold approximation and projection (UMAP) plot showing all single cells of the live Lin- and CD34+ events selected from down sampled files concatenated at T0 and T1. The three clusters upregulated at T1 are CD45dim clusters, confirming our results. In conclusion, using a flow cytometry approach, we demonstrated in A-TAH-transplanted patients a significant mobilization of Lin-CD34+CD45dim in peripheral blood one month after A-TAH implantation. Using a flow cytometry approach, we demonstrated in A-TAH transplanted patients a significant mobilization of Lin-CD34+CD45dim in peripheral blood one month after A-TAH implantation. This cell population could be at the origin of newly formed endothelial cells on top of hybrid membrane in Carmat bioprosthetic total artificial heart.

Pharmacological management of obstructive peripheral arterial disease: two case reports.

Peripheral artery disease (PAD), also abbreviated as LEAD or lower extremity artery disease, is an important predictor of cardiovascular morbidity and mortality. Rivaroxaban, a selective direct factor Xa inhibitor, is proposed as an additional pharmacologic option for managing this disease. Two patients presented with PAD and high-risk comorbidities. The first case showed how the evaluation of the cardiovascular risk guided the therapeutic management of the patient. The second case was about a patient diagnosed with LEAD who experienced worsening from exertional ischemia toward critical ischemia requiring amputation despite distal revascularization, and parenteral vasodilator therapy to relieve pain. This case suggested a comprehensive care management approach, adapted to PAD progression stages. The PAD management consists nowadays of optimizing the management of cardiovascular risk factors and disease progression. Diagnosis, treatment, monitoring, and patient education should be handled by a vascular specialist in a specialized care unit.

Interleukin-8 Receptors CXCR1 and CXCR2 Are Not Expressed by Endothelial Colony-forming Cells.

Endothelial colony-forming cells (ECFCs) are human vasculogenic cells described as potential cell therapy product and good candidates for being a vascular liquid biopsy. Since interleukin-8 (IL-8) is a main actor in senescence, its ability to interact with ECFCs has been explored. However, expression of CXCR1 and CXCR2, the two cellular receptors for IL-8, by ECFCs remain controversial as several teams published contradictory reports. Using complementary technical approaches, we have investigated the presence of these receptors on ECFCs isolated from cord blood. First, CXCR1 and CXCR2 were not detected on several clones of cord blood- endothelial colony-forming cell using different antibodies available, in contrast to well-known positive cells. We then compared the RT-PCR primers used in different papers to search for the presence of CXCR1 and CXCR2 mRNA and found that several primer pairs used could lead to non-specific DNA amplification. Last, we confirmed those results by RNA sequencing. CXCR1 and CXCR2 were not detected in ECFCs in contrary to human-induced pluripotent stem cell-derived endothelial cells (h-iECs). In conclusion, using three different approaches, we confirmed that CXCR1 and CXCR2 were not expressed at mRNA or protein level by ECFCs. Thus, IL-8 secretion by ECFCs, its effects in angiogenesis and their involvement in senescent process need to be reanalyzed according to this absence of CXCR-1 and - 2 in ECFCs.Graphical Abstract.

Acute Digital Ischemia After Arterial Injection of Crushed Zolpidem Tablets: Role of Microcrystalline Cellulose? A Case Report.

Literature is scarce on acute ischemia after intra-arterial injection of crushed tablets and no effective medical treatment against the progression of lesions is reported. The only factor able to modify the outcome is the delay between injection and management by a specialized vascular team. Moreover the risk of necrosis seems higher after benzodiazepine intra-arterial injection than with other drugs. We tried to find out mechanistic explanations. We report on the case of a 31-year-old drug addict woman who self-injected into her left brachial artery crushed tablets of zolpidem. She developed an acute ischemia of the left hand, with necrosis of the intermediate and distal phalanges of fingers II, III, and IV. Angiogram of the left upper arm confirmed the distal arterial occlusions with no run-off after the palmar arch in the necrotic fingers. Once she was admitted into our vascular unit, intravenous vasodilator therapy by iloprost, heparin and local protective care were rapidly introduced. After delineation between living and necrotic tissues, she required distal amputations of the affected fingers. The clinical severity of arterial injections of benzodiazepine tablets is linked to the association of several pathophysiological mechanisms. Rather than related benzodiazepine pharmacologic effects with tissue ischemia, by the inhibition of phosphodiesterase, a vasodilator intermediate, or through the peripheral benzodiazepine-type receptor, the predominant mechanism is more likely in relation with microcrystalline cellulose, one component of zolpidem tablets, known as potential embolic agents. They are insoluble and resistant to degradation in water. These properties are probably prominent in the case we described here. Through this case report we want to drag attention of physicians in charge of a patient with acute ischemia after crushed tablet accidental intra-arterial injection, not only to look at the drug injected but also the other components of the tablet and especially to microcrystalline cellulose.