Publications by authors named "Lucia Mazzolai"

179 Publications

Pulmonary Embolism in Patients with COVID-19: Comparison between Different Care Settings.

Semin Thromb Hemost 2021 Dec 13. Epub 2021 Dec 13.

Department of Internal Medicine, Hospital Universitari Germans Trias i Pujol. Badalona, Barcelona, Spain.

The clinical characteristics and outcomes of patients with coronavirus disease 2019 (COVID-19) who develop pulmonary embolism (PE) in the full spectrum of patient care settings need to be elucidated. The aim of this study was to compare the clinical characteristics, treatment, and 90-day outcomes in patients diagnosed with PE while recovering from COVID-19 in the outpatient setting versus those who were diagnosed with PE while being hospitalized with COVID-19. Data from the international Registro Informatizado de Enfermedad TromboEmbólica (RIETE) registry were used. The major study outcomes were all-cause death, major bleeding, and venous thromboembolism (VTE) recurrences during the first 90 days after PE. From March 2020 to March 2021, 737 patients with COVID-19 experienced acute PE. Of these, 340 (46%) were recovering from COVID-19 as outpatients (267 patients who had been treated at home for COVID-19 and 73 discharged after being hospitalized with COVID-19). Compared with inpatients with COVID-19, those recovering in the outpatient setting upon PE were less likely to be men (odds ratio [OR]: 0.54; 95% confidence interval [CI]: 0.40-0.72) and less likely to have hypertension (OR: 0.55; 95% CI: 0.41-0.74) or diabetes (OR: 0.51; 95% CI: 0.33-0.76). At 90-day follow-up, eight patients (none recovering from COVID-19 as outpatient vs. 2.4% of inpatients with COVID-19) developed recurrent VTE, 34 (1.9 vs. 7.9%) had major bleeding, and 128 (10 vs. 24%) died. On multivariable analysis, inpatients with COVID-19 were at a higher risk of major bleeding (adjusted hazard ratio [HR]: 6.80; 95% CI: 1.52-30.4) or death (adjusted HR: 2.24; 95% CI: 1.40-3.58). In conclusion, using a large multinational registry of patients with COVID-19 who experienced PE, thromboembolic episodes occurring in those recovering from COVID-19 as outpatients were associated with less ominous outcomes than inpatients with COVID-19.
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http://dx.doi.org/10.1055/s-0041-1740152DOI Listing
December 2021

Indocyanine green lymphography as novel tool to assess lymphatics in patients with lipedema.

Microvasc Res 2021 Dec 9;140:104298. Epub 2021 Dec 9.

Angiology Division, Heart and Vessel Department, Lausanne University Hospital, University of Lausanne, Lausanne, Switzerland. Electronic address:

Objective: Lipedema is a chronic and progressive disease associated with lymphatic impairment at later stages. The aim of our study was to describe the functional status and anatomy of lower limb superficial lymphatic system using indocyanine green (ICG) lymphography in patients with lipedema.

Methods: Following ICG injection at the dorsum of the foot, distance (cm) covered by the dye at 10 (T10') and 25 min (T25') was measured and normalized for limb length. If the dye did not reach the groin within 25 min, patients were classified as "drainage-needing" group (DNG). Values of fat and lean distribution assessed by dual-energy X-ray absorptiometry were extracted, and correlation analysis was performed. Furthermore, anatomical patterns of superficial lymphatics were assessed.

Results: Overall, 45 women were included, 25 (56%) of whom were classified as DNG. Symptoms duration was significantly associated with DNG status at multivariate analysis (odds ratio 1.07; 95% CI 1.01-1.14; p = 0.047). Moreover, Spearman's analysis showed a negative correlation between symptoms duration and T25' dye migration (r = -0.469; p = 0.037). Overall, no major anatomical lymphatic changes were found.

Conclusions: Present study suggests that lymphatic functioning in patients with lipedema correlates with symptoms duration. Further research on larger cohorts should verify our findings and clarify their potential therapeutic implications. Overall, ICG lymphography may be promising technique to assess both lymphatic anatomy and functioning in patients with lipedema.
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http://dx.doi.org/10.1016/j.mvr.2021.104298DOI Listing
December 2021

Supervised Exercise Training Improves 6 min Walking Distance and Modifies Gait Pattern during Pain-Free Walking Condition in Patients with Symptomatic Lower Extremity Peripheral Artery Disease.

Sensors (Basel) 2021 Nov 30;21(23). Epub 2021 Nov 30.

Institute of Sport Sciences, University of Lausanne, 1015 Lausanne, Switzerland.

This study aimed to investigate the effects of supervised exercise training (SET) on spatiotemporal gait and foot kinematics parameters in patients with symptomatic lower extremity peripheral artery disease (PAD) during a 6 min walk test. Symptomatic patients with chronic PAD (Fontaine stage II) following a 3 month SET program were included. Prior to and following SET, a 6 min walk test was performed to assess the 6 min walking distance (6MWD) of each patient. During this test, spatiotemporal gait and foot kinematics parameters were assessed during pain-free and painful walking conditions. Twenty-nine patients with PAD (65.4 ± 9.9 years.) were included. The 6MWD was significantly increased following SET (+10%; ≤ 0.001). The walking speed (+8%) and stride frequency (+5%) were significantly increased after SET ( ≤ 0.026). The stride length was only significantly increased during the pain-free walking condition (+4%, = 0.001), whereas no significant differences were observed during the condition of painful walking. Similarly, following SET, the relative duration of the loading response increased (+12%), the relative duration of the foot-flat phase decreased (-3%), and the toe-off pitch angle significantly increased (+3%) during the pain-free walking condition alone ( ≤ 0.05). A significant positive correlation was found between changes in the stride length (r = 0.497, = 0.007) and stride frequency (r = 0.786, ≤ 0.001) during pain-free walking condition and changes in the 6MWD. A significant negative correlation was found between changes in the foot-flat phase during pain-free walking condition and changes in the 6MWD (r = -0.567, = 0.002). SET was found to modify the gait pattern of patients with symptomatic PAD, and many of these changes were found to occur during pain-free walking. The improvement in individuals' functional 6 min walk test was related to changes in their gait pattern.
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http://dx.doi.org/10.3390/s21237989DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8659842PMC
November 2021

[Venous thromboembolic disease during pregnancy : diagnosis, treatment and follow-up].

Rev Med Suisse 2021 Dec;17(762):2135-2138

Service d'angiologie, Département cœur-vaisseaux, Centre hospitalier universitaire vaudois, 1011 Lausanne.

Venous thromboembolism is a leading cause of maternal morbidity and mortality with an overall incidence of 1-2 cases per 1000 pregnancies. The purpose of this article is to summarize more recent recommendations for the management of venous thromboembolism during pregnancy and post-partum period.
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December 2021

[Who do you screen for an abdominal aortic aneurysm ?]

Rev Med Suisse 2021 Dec;17(762):2132-2134

Service d'angiologie, Département cœur-vaisseaux, Centre hospitalier universitaire vaudois, 1011 Lausanne.

Abdominal aortic aneurysm (AAA) represents an important public health problem. The early detection and treatment as well as follow-up of an AAA are important to reduce the high mortality rate associated with its rupture. Despite the decline of the prevalence of AAA in the last decades, the latest international recommendations have reaffirmed that screening in men remains cost-effective. In contrast, the data and recommendations for women are unclear. The best method for AAA screening is abdominal ultrasound. The aim of this paper is to present an up-to-date review of the indications for AAA screening based on the latest recommendations.
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December 2021

[Vascular passport : a tool for secondary prevention among patients with peripheral artery disease].

Rev Med Suisse 2021 Dec;17(762):2128-2131

Service d'angiologie, Département cœur-vaisseaux, Centre hospitalier universitaire vaudois, 1011 Lausanne.

Peripheral arterial disease (PAD) is a major health problem in Switzerland, as myocardial infarction or stroke, all three sharing common cardiovascular (CV) risk factors and similar pathophysiological mechanisms (atherosclerosis). Unfortunately, PAD is still often overlooked, despite being fraught with significant morbidity/mortality and increasing the patient's overall CV risk. It is therefore essential to improve secondary prevention in order to decrease this burden and the overall CV risk of the patient. We will review the treatment targets for CV risk factors as secondary prevention in patients with PAD and see how the use of a vascular passport may improve management.
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December 2021

[Screening for peripheral arterial disease : role of the primary care physician].

Rev Med Suisse 2021 Dec;17(762):2123-2127

Service d'angiologie, Département cœur-vaisseaux, Centre hospitalier universitaire vaudois, 1011 Lausanne.

Peripheral arterial disease (PAD) is a widespread disease with high impact on global health. While general population screening is not currently indicated, the primary care physician has the critical role of identifying asymptomatic patients who are particularly at risk for PAD and could therefore benefit from screening. In addition, he or she must recognize the typical and atypical clinical presentations of patients with symptomatic PAD to ensure proper diagnosis and care. After an adequate medical history and clinical examination, the first diagnostic test is the « Ankle-Brachial Index » (ABI) calculation. In case of pathologic ABI (≤ 0.9, or > 1.4), or in case of normal or borderline ABI with symptoms, the patient should be referred to a vascular medicine physician for diagnostic confirmation and management.
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December 2021

[Subclinical atherosclerosis in hypercholesterolemia - Towards a personalized, shared decision-making cardiovascular prevention].

Rev Med Suisse 2021 Dec;17(762):2117-2122

Service d'angiologie, Département cœur-vaisseaux, Centre hospitalier universitaire vaudois, 1011 Lausanne.

Identification of subjects at increased cardiovascular risk (CV) using traditional risk calculators is established. Nevertheless, up to 50% of CV events occur in people classified as intermediate risk. Non-invasive atherosclerosis (ATS) assessment with carotid/femoral US and coronary artery calcium score, offers the opportunity of a personalized prevention. ATS detection could be useful in improving CV risk stratification, in optimizing individual therapeutic management and in promoting a shared decision-making process. Is this the era of a paradigm shift in CV-risk prediction? The fascinating question is still open, but the increasing number of evidences shed new insights for our everyday clinical practice. Here we strive to provide an updated scenario on the use of ATS imaging in the CV risk evaluation and therapeutic decision.
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December 2021

Détection de l’ athérosclérose asymptomatique, y-a-t-il une place en pratique quotidienne ?

Rev Med Suisse 2021 Dec;17(762):2115

Service d'angiologie et d'hémostase, Hôpitaux universitaires de Genève, Genève.

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December 2021

Descending stair walking in patients with symptomatic lower extremity peripheral artery disease: A pilot study.

Vasc Med 2021 Dec 5:1358863X211058784. Epub 2021 Dec 5.

Institute of Sport Sciences, University of Lausanne, Lausanne, Vaud, Switzerland.

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http://dx.doi.org/10.1177/1358863X211058784DOI Listing
December 2021

Role of age, sex, and specific provoking factors on the distal versus proximal presentation of first symptomatic deep vein thrombosis: analysis of the SWIss Venous ThromboEmbolism Registry (SWIVTER).

Intern Emerg Med 2021 Nov 3. Epub 2021 Nov 3.

Department of Angiology, University Hospital Zurich, Raemistrasse 100, RAE C 13, 8091, Zurich, Switzerland.

We aimed to evaluate the impact of age, sex, and their interactions with provoking risk factors for deep vein thrombosis (DVT). In addition, we intended to provide additional insights on risk factors associated with the isolated distal versus proximal presentation of first symptomatic acute DVT, both being characterized by different prognosis. In the present analysis from the SWIss Venous ThromboEmbolism Registry (SWIVTER), we compared demographic and baseline characteristics in patients with isolated distal (n = 184; 35%) versus proximal (n = 346) DVT of the lower limbs without symptomatic pulmonary embolism, and identified factors related with the presenting thrombosis location. In the overall population, mean age was 59 ± 19 years, 266 (50%) were women, 106 (20%) patients had cancer, 86 (16%) recent surgery, and 52 (10%) acute infection/sepsis. In a multivariable analysis, recent surgery [odds ratio (OR) 2.92, 95% confidence interval (CI) 1.80-4.73] was independently associated with a diagnosis of isolated distal DVT, whereas cancer (OR 2.01, 95% CI 1.20-3.35), male sex aged 41 to 75 years (OR 2.21, 95% CI 1.33-3.67), and acute infection/sepsis (OR 2.71, 95% CI 1.29-5.66) with a diagnosis of proximal DVT. In SWIVTER, age, sex, and several provoking risk factors for VTE appeared to be related with the presenting location of first symptomatic DVT. Cancer, male sex, and acute infection/sepsis were associated with a proximal location of DVT, whereas recent surgery was associated with a distal presentation, likely acting as confounders for the association between thrombosis location and prognosis.
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http://dx.doi.org/10.1007/s11739-021-02878-7DOI Listing
November 2021

Intensity-dependent effects of exercise therapy on walking performance and aerobic fitness in symptomatic patients with lower-extremity peripheral artery disease: A systematic review and meta-analysis.

Vasc Med 2021 Sep 28:1358863X211034577. Epub 2021 Sep 28.

Division of Angiology, Heart and Vessel Department, Lausanne University Hospital, Switzerland.

We investigated how nonpain-based exercise therapy intensity (light-to-moderate or vigorous) affects improvements in walking performance and cardiorespiratory fitness of patients with symptomatic lower-extremity peripheral artery disease (PAD). We searched the Embase, MEDLINE, Cochrane, Web of Science, and Google Scholar databases up to April 2021 and included randomized controlled trials reporting training therapies targeting exercise intensity (heart rate, oxygen consumption, or perceived exertion). The main outcomes were walking performance (pain-free [PFWD] and maximal [MWD] walking distance) and cardiorespiratory fitness (V̇O). Secondary subanalyses examined the training modality (walking or other modalities) and the approach (high-intensity interval or moderate-intensity training). A total of 1132 patients were included. Light-to-moderate was superior to vigorous exercise intensity in improving MWD (223 m [95% CI 174 to 271], < 0.00001; 153 m [95% CI 113 to 193], < 0.00001; respectively) and PFWD (130 m [95% CI 87 to 173], < 0.00001; 83 m [95% CI 61 to 104], < 0.00001; respectively). When training modalities were considered, walking at a vigorous intensity (272 m [95% CI 207 to 337], < 0.00001) showed the largest improvement in MWD compared to other exercise modalities. A larger increase in V̇O was observed following vigorous (3.0 mL O·kg·min [95% CI 2.4 to 3.6], < 0.00001) compared to light-to-moderate (1.1 mL O·kg·min [95% CI 0.4 to 1.7], = 0.001) exercise intensity. These results indicate that vigorous was less effective than light-to-moderate intensity in improving walking performance, whereas it was more effective in improving V̇O. When the training modalities were considered, walking at a vigorous intensity showed the greatest improvement in MWD. .
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http://dx.doi.org/10.1177/1358863X211034577DOI Listing
September 2021

Exercise Prior to Lower Extremity Peripheral Artery Disease Improves Endurance Capacity and Hindlimb Blood Flow by Inhibiting Muscle Inflammation.

Front Cardiovasc Med 2021 4;8:706491. Epub 2021 Aug 4.

Division of Angiology, Heart and Vessel Department, University Hospital of Lausanne (CHUV), Lausanne, Switzerland.

Lower extremity peripheral artery disease (PAD) is associated with functional decline. Physical exercise has been proven to be an effective therapeutic strategy for PAD; however the effect of exercise initiated before PAD remains unknown. Here, we investigated the preventive effects of exercise on endurance capacity, hindlimb perfusion, and on polarization profile of circulating monocytes and limb muscle macrophages. ApoE mice were subjected to 5-week running wheel exercise or remained sedentary before induction of hindlimb ischemia. The two groups were thereafter kept sedentary. Exercised mice prior to PAD showed higher exhaustive treadmill running distance and time than sedentary mice. Preventive exercise also increased perfusion, arteriole density, and muscle regeneration in the ischemic hindlimb. Moreover, preventive exercise prevented ischemia-induced increased gene expression of pro-inflammatory M1 macrophages markers and cytokines in the ischemic muscle, while no changes were observed for anti-inflammatory M2 macrophage markers. Flow cytometry analysis showed that the proportion of circulating pro-inflammatory monocyte subtype decreased whereas that of anti-inflammatory monocytes increased with preventive exercise. Overall, we show that exercise initiated before PAD improves endurance performance and hindlimb perfusion in mice probably inhibition of M1 macrophage polarization and inflammation in the ischemic muscle. Our study provides experimental evidence for a role of regular exercise in primary prevention of PAD.
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http://dx.doi.org/10.3389/fcvm.2021.706491DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8371529PMC
August 2021

The effects of COVID-19 pandemic on patients with lower extremity peripheral arterial disease: A near miss disaster.

Ann Vasc Surg 2021 Nov 16;77:71-78. Epub 2021 Aug 16.

Angiology Division, Heart and Vessels Department, Lausanne University Hospital, University of Lausanne, Lausanne, Switzerland. Electronic address:

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, to May 11, 2020, compared to the same time frames in 2018 to 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 to 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 to 2019 (47.5% vs. 24.6%; P = 0.006). Overall, the types of surgery were similar between 2020 and 2018 to 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.
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http://dx.doi.org/10.1016/j.avsg.2021.07.006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8366045PMC
November 2021

Improvement in 6-Minute Walking Distance after Supervised Exercise Training Is Related to Changes in Quality of Life in Patients with Lower Extremity Peripheral Artery Disease.

J Clin Med 2021 Jul 28;10(15). Epub 2021 Jul 28.

Heart and Vessel Department, Division of Angiology, Lausanne University Hospital, 1011 Lausanne, Switzerland.

This study aimed to investigate the relationship between supervised exercise training (SET)-induced changes in treadmill performance and 6 min walking distance, and changes in general (physical and mental) self-perceived health-related quality of life (HRQoL) in symptomatic patients with lower extremity peripheral artery disease (PAD). This is an observational study investigating Fontaine stage II PAD patients participating in 3-month SET. Before and following SET, treadmill performance (pain-free (PFWD) and maximal (MWD)), and 6 min walking distance (6MWD) were assessed. Self-perceived HRQoL was assessed with the Medical Outcomes Study Short-Form 36 (SF-36). Ankle- and toe-brachial indexes were also measured. One-hundred forty-seven patients with PAD were included (64.9 ± 9.6 y, 70% men). After SET, PFWD (+102%, ≤ 0.001), MWD (+87%, ≤ 0.001), and 6MWD (+14%, ≤ 0.001) significantly increased. All eight SF-36 subscale scores significantly improved following SET ( ≤ 0.04). SET significantly improved physical and mental component summaries of the SF-36 ( ≤ 0.001). Larger increases in 6MWD were associated with greater improvements in physical ( = 0.19; = 0.02) and mental ( = 0.24; = 0.005) component summaries of the SF-36. No significant relationship was observed between changes in treadmill performance and changes in physical and mental component summaries of the SF-36. These results show that improvements in 6MWD following SET are related to improvements in general self-perceived HRQoL in patients with symptomatic lower extremity PAD. On the contrary, changes in treadmill performance were not related to improvements in HRQoL. These results suggest that the 6 min walking test is an essential outcome measure to assess overall patient functional status following interventions in patients with PAD.
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http://dx.doi.org/10.3390/jcm10153330DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8348496PMC
July 2021

Antithrombotic therapies in aortic and peripheral arterial diseases in 2021: a consensus document from the ESC working group on aorta and peripheral vascular diseases, the ESC working group on thrombosis, and the ESC working group on cardiovascular pharmacotherapy.

Eur Heart J 2021 10;42(39):4013-4024

Cardiothoracic and Vascular Department, Azienda OspedalieroUniversitaria Pisana, Pisa, Italy.

The aim of this collaborative document is to provide an update for clinicians on best antithrombotic strategies in patients with aortic and/or peripheral arterial diseases. Antithrombotic therapy is a pillar of optimal medical treatment for these patients at very high cardiovascular risk. While the number of trials on antithrombotic therapies in patients with aortic or peripheral arterial diseases is substantially smaller than for those with coronary artery disease, recent evidence deserves to be incorporated into clinical practice. In the absence of specific indications for chronic oral anticoagulation due to concomitant cardiovascular disease, a single antiplatelet agent is the basis for long-term antithrombotic treatment in patients with aortic or peripheral arterial diseases. Its association with another antiplatelet agent or low-dose anticoagulants will be discussed, based on patient's ischaemic and bleeding risk as well therapeutic paths (e.g. endovascular therapy). This consensus document aims to provide a guidance for antithrombotic therapy according to arterial disease localizations and clinical presentation. However, it cannot substitute multidisciplinary team discussions, which are particularly important in patients with uncertain ischaemic/bleeding balance. Importantly, since this balance evolves over time in an individual patient, a regular reassessment of the antithrombotic therapy is of paramount importance.
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http://dx.doi.org/10.1093/eurheartj/ehab390DOI Listing
October 2021

Second consensus document on diagnosis and management of acute deep vein thrombosis: updated document elaborated by the ESC Working Group on aorta and peripheral vascular diseases and the ESC Working Group on pulmonary circulation and right ventricular function.

Eur J Prev Cardiol 2021 Jul 13. Epub 2021 Jul 13.

Department of Cardiology, Dupuytren University Hospital and Inserm 1094, Tropical Neuroepidemiology, School of Medicine, 2 avenue martin Luther-King 87042 Limoges, France.

This consensus document is proposed to clinicians to provide the whole spectrum of deep vein thrombosis management as an update to the 2017 consensus document. New data guiding clinicians in indicating extended anticoagulation, management of patients with cancer, and prevention and management of post-thrombotic syndrome are presented. More data on benefit and safety of non-vitamin K antagonists oral anticoagulants are highlighted, along with the arrival of new antidotes for severe bleeding management.
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http://dx.doi.org/10.1093/eurjpc/zwab088DOI Listing
July 2021

High-intensity exercise in hypoxia improves endothelial function via increased nitric oxide bioavailability in C57BL/6 mice.

Acta Physiol (Oxf) 2021 10 19;233(2):e13700. Epub 2021 Jun 19.

Institute of Sport Sciences, University of Lausanne, Lausanne, Switzerland.

Aim: The optimal exercise intensity to improve endothelial function remains unclear, as well as whether the addition of hypoxia could potentiate this function. Therefore, the aim of this study was to compare the effects of different exercise intensities in normoxia and hypoxia on vascular reactivity and nitric oxide (NO) bioavailability in mice.

Methods: C57BL/6 mice underwent treadmill running three times per week, for 4 weeks at either low, maximal or supramaximal intensity in normoxia or hypoxia (inspire oxygen fraction = 0.13). Vascular reactivity and expression of genes and proteins involved in NO production/bioavailability were assessed in aorta using isolated vessel tension experiments, RT-qPCR and western blot, respectively. Circulating NO metabolites and pro-/antioxidant markers were measured.

Results: Hypoxic exercise improved both acetylcholine-induced vasorelaxation and phenylephrine-induced vasoconstriction compared to normoxic exercise, independently of intensity. In hypoxia, a higher acetylcholine-induced vasorelaxation was observed with high intensities (supramaximal and maximal) compared to low intensity. Exercise protocols modulated endothelial nitric oxide synthase (eNOS) and α1-adrenergic receptor (α -AR) mRNA level, but not superoxide dismutase 3 (SOD3) and p47phox. No significant differences were observed for protein expression of α -AR, total eNOS, phosphorylated eNOS, SOD isoforms and p47phox. However, plasma SOD and catalase activities were significantly increased in hypoxic supramaximal compared to hypoxic low intensity, while concentration of nitrotyrosine significantly decreased. The latter was also observed in hypoxic maximal and supramaximal compared to the same intensities in normoxia.

Conclusion: Hypoxic high-intensity exercise increases NO bioavailability and improves vascular function, opening promising clinical perspectives for cardiovascular disease prevention.
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http://dx.doi.org/10.1111/apha.13700DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8518730PMC
October 2021

Multimodal Supervised Exercise Training Is Effective in Improving Long Term Walking Performance in Patients with Symptomatic Lower Extremity Peripheral Artery Disease.

J Clin Med 2021 May 11;10(10). Epub 2021 May 11.

Division of Angiology, Heart and Vessel Department, Lausanne University Hospital, 1011 Lausanne, Switzerland.

This study aimed to evaluate the effect of a multimodal supervised exercise training (SET) program on walking performance for 12 months in patients with symptomatic lower extremity peripheral artery disease (PAD). Consecutive patients with Fontaine stage II PAD participating in the SET program of our hospital were retrospectively investigated. Walking performance, assessed using a treadmill with measures of the pain-free and maximal walking distance (PFWD, MWD, respectively), and 6 min walking distance (6MWD), were tested before and following SET, as well as at 6 and 12 months after SET completion. Ninety-three symptomatic patients with PAD (65.0 ± 1.1 y) were included in the study. Following SET, the walking performance significantly improved (PFWD: +145%, ≤ 0.001; MWD: +97%, ≤ 0.001; 6MWD: +15%, ≤ 0.001). At 6 months, PFWD (+257%, ≤ 0.001), MWD (+132%, ≤ 0.001), and 6MWD (+11%, ≤ 0.001) remained significantly improved compared with the pre-SET condition. At 12 months, PFWD (+272%, ≤ 0.001), MWD (+130%, ≤ 0.001), and 6MWD (+11%, ≤ 0.001) remained significantly improved compared with the pre-training condition. The walking performance remained significantly improved in both women and men for up to 12 months ( ≤ 0.001). Multimodal SET is effective at improving walking performance in symptomatic patients with PAD, with improvements lasting up to 12 months.
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http://dx.doi.org/10.3390/jcm10102057DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8151788PMC
May 2021

What Is Currently the Role of TcPO2 in the Choice of the Amputation Level of Lower Limbs? A Comprehensive Review.

J Clin Med 2021 Apr 1;10(7). Epub 2021 Apr 1.

Service d'Angiologie, Département Coeur et Vaisseaux, Centre Hospitalier Universitaire Vaudois, 1011 Lausanne, Switzerland.

Some patients still require major amputation for lower extremity peripheral arterial disease treatment. The purpose of pre-operative amputation level selection is to determine the most distal amputation site with the highest healing probability without re-amputation. Transcutaneous oximetry (TcPO2) can detect viable tissue with the highest probability of healing. Several factors affect the accuracy of TcPO2; nevertheless, surgeons rely on TcPO2 values to determine the optimal amputation level. Background about the development of TcPO2, methods of measurement, consequences of lower limb amputation level, and the place of TcPO2 in the choice of the amputation level are reviewed herein. Most of the retrospective studies indicated that calf TcPO2 values greater than 40 mmHg were associated with a high percentage of successful wound healing after below-knee-amputation, whereas values lower than 20 mmHg indicated an increased risk of unsuccessful healing. However, a consensus on the precise cut-off value of TcPO2 necessary to assure healing is missing. Ways of improvement for TcPO2 performance applied to the optimization of the amputation-level are reported herein. Further prospective data are needed to better approach a TcPO2 value that will promise an acceptable risk of re-amputation. Standardized TcPO2 measurement is crucial to ensure quality of data.
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http://dx.doi.org/10.3390/jcm10071413DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8037184PMC
April 2021

Progress in aorta and peripheral cardiovascular disease research.

Cardiovasc Res 2021 07;117(9):2045-2053

Department of Cardiology, Dupuytren-2 University Hospital, and Inserm 1094 & IRD, Limoges University, Limoges, France.

Although coronavirus disease 2019 seems to be the leading topic in research number of outstanding studies have been published in the field of aorta and peripheral vascular diseases likely affecting our clinical practice in the near future. This review article highlights key research on vascular diseases published in 2020. Some studies have shed light in the pathophysiology of aortic aneurysm and dissection suggesting a potential role for kinase inhibitors as new therapeutic options. A first proteogenomic study on fibromuscular dysplasia (FMD) revealed a promising novel disease gene and provided proof-of-concept for a protein/lipid-based FMD blood test. The role of NADPH oxidases in vascular physiology, and particularly endothelial cell differentiation, is highlighted with potential for cell therapy development. Imaging of vulnerable plaque has been an intense field of research. Features of plaque vulnerability on magnetic resonance imaging as an under-recognized cause of stroke are discussed. Major clinical trials on lower extremity peripheral artery disease have shown added benefit of dual antithrombotic (aspirin plus rivaroxaban) treatment.
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http://dx.doi.org/10.1093/cvr/cvab144DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8600478PMC
July 2021

The atherosclerosis burden score.

Vasa 2021 Jul 1;50(4):280-285. Epub 2021 Apr 1.

Angiology, University Hospital CHUV, Lausanne, Switzerland.

We carried out this study to evaluate the predictive value of atherosclerosis burden score (ABS) to predict coronary artery disease (CAD) among asymptomatic patients without known cardiovascular disease (CVD), as compared to other imaging or functional techniques, namely coronary artery calcium (CAC) score, carotid intima-media thickness (C-IMT), and ankle brachial index (ABI). This prospective study included 198 asymptomatic consecutive patients referred for evaluation of their cardiovascular (CV) risk and for therapeutic advice. Traditional CV risk factors, ABS, CAC score, C-IMT, ABI and an ECG-synchronized coronary CT-angiography (CCTA) were performed for each patient. We compared the predictive values of these atherosclerosis markers to detect CAD defined as coronary stenosis ≥30% objectivated by CCTA. Among the whole sample, the area under the receiver-operating characteristic curve (ROC-AUC) was significantly higher for CAC score (0.81, p=0.015) than for ABS, the reference (0.70) but these values were lower for C-IMT (0.60, p=0.16) and particularly for ABI (0.56, p=0.0015). However, among patients at intermediate risk of coronary heart disease (CHD), according to Framingham risk score (FRS), the differences between the ROC-AUC values for ABS (0.70) and CAC score (0.76, p=0.36) were less pronounced. Again, as compared to ABS, the ROC-AUC values were lower for C-IMT (0.60, p=0.21) and ABI (0.57, p=0.06). ABS, an ultrasonographic score based on the assessment of carotid and femoral plaque burden, predicts more accurately CAD than other non-radiation tools analyzed here, and has a similar performance to CAC in patients at intermediate CHD risk. Thus, ABS could be an appropriate non-invasive and safe method to improve the detection of high-risk patients who will benefit from a more intensive therapy for the primary prevention of CVD.
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http://dx.doi.org/10.1024/0301-1526/a000949DOI Listing
July 2021

Post-thrombotic syndrome.

Vasa 2021 Sep 15;50(5):331-340. Epub 2021 Mar 15.

Arianna Foundation, Bologna, Italy.

Post-thrombotic syndrome (PTS) is a chronic venous insufficiency manifestation following an episode of deep-vein thrombosis (DVT). It is an important and frequent long-term adverse event of proximal DVT affecting 20-50% of patients. This position paper integrates data guiding clinicians in deciding PTS diagnosis, treatment and follow-up.
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http://dx.doi.org/10.1024/0301-1526/a000946DOI Listing
September 2021

The effect of microgravity on the human venous system and blood coagulation: a systematic review.

Exp Physiol 2021 May 25;106(5):1149-1158. Epub 2021 Mar 25.

Space Medicine Team, European Astronaut Centre, European Space Agency (ESA), Cologne, Germany.

New Findings: What is the central question of this study? Recently, an internal jugular venous thrombus was identified during spaceflight: does microgravity induce venous and/or coagulation pathophysiology, and thus an increased risk of venous thromboembolism (VTE)? What is the main finding and its importance? Whilst data are limited, this systematic review suggests that microgravity and its analogues may induce an enhanced coagulation state due to venous changes most prominent in the cephalad venous system, as a consequence of changes in venous flow, distension, pressures, endothelial damage and possibly hypercoagulability in microgravity and its analogues. However, whether such changes precipitate an increased VTE risk in spaceflight remains to be determined.

Abstract: Recently, an internal jugular venous thrombus was identified during spaceflight, but whether microgravity induces venous and/or coagulation pathophysiology, and thus, an increased risk of venous thromboembolism (VTE) is unclear. Therefore, a systematic (Cochrane compliant) review was performed of venous system or coagulation parameters in actual spaceflight (microgravity) or ground-based analogues in PubMed, MEDLINE, Ovid EMBASE, Cochrane Library, European Space Agency, National Aeronautics and Space Administration, and Deutsches Zentrum für Luft-und Raumfahrt databases. Seven-hundred and eight articles were retrieved, of which 26 were included for evaluation with 21 evaluating venous, and five coagulation parameters. Nine articles contained spaceflight data, whereas the rest reported ground-based analogue data. There is substantial variability in study design, objectives and outcomes. Yet, data suggested cephalad venous system dilatation, increased venous pressures and decreased/reversed flow in microgravity. Increased fibrinogen levels, presence of thrombin generation markers and endothelial damage were also reported. Limited human venous and coagulation system data exist in spaceflight, or its analogues. Nevertheless, data suggest spaceflight may induce an enhanced coagulation state in the cephalad venous system, as a consequence of changes in venous flow, distension, pressures, endothelial damage and possibly hypercoagulability. Whether such changes precipitate an increased VTE risk in spaceflight remains to be determined.
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http://dx.doi.org/10.1113/EP089409DOI Listing
May 2021

Management of carotid stenosis for primary and secondary prevention of stroke: state-of-the-art 2020: a critical review.

Eur Heart J Suppl 2020 Nov 6;22(Suppl M):M35-M42. Epub 2020 Dec 6.

Department of Cardiology, Dupuytren University Hospital, INSERM 1094 & IRD, Limoges, France.

Carotid atherosclerotic plaque is encountered frequently in patients at high cardiovascular risk, especially in the elderly. When plaque reaches 50% of carotid lumen, it induces haemodynamically significant carotid stenosis, for which management is currently at a turning point. Improved control of blood pressure, smoking ban campaigns, and the widespread use of statins have reduced the risk of cerebral infarction to <1% per year. However, about 15% of strokes are still secondary to a carotid stenosis, which can potentially be detected by effective imaging techniques. For symptomatic carotid stenosis, current ESC guidelines put a threshold of 70% for formal indication for revascularization. A revascularization should be discussed for symptomatic stenosis over 50% and for asymptomatic carotid stenosis over 60%. This evaluation should be performed by ultrasound as a first-line examination. As a complement, computed tomography angiography (CTA) and/or magnetic resonance angiography are recommended for evaluating the extent and severity of extracranial carotid stenosis. In perspective, new high-risk markers are currently being developed using markers of plaque neovascularization, plaque inflammation, or plaque tissue stiffness. Medical management of patient with carotid stenosis is always warranted and applied to any patient with atheromatous lesions. Best medical therapy is based on cardiovascular risk factors correction, including lifestyle intervention and a pharmacological treatment. It is based on the tri-therapy strategy with antiplatelet, statins, and ACE inhibitors. The indications for carotid endarterectomy (CEA) and carotid artery stenting (CAS) are similar: for symptomatic patients (recent stroke or transient ischaemic attack ) if stenosis >50%; for asymptomatic patients: tight stenosis (>60%) and a perceived high long-term risk of stroke (determined mainly by imaging criteria). Choice of procedure may be influenced by anatomy (high stenosis, difficult CAS or CEA access, incomplete circle of Willis), prior illness or treatment (radiotherapy, other neck surgery), or patient risk (unable to lie flat, poor AHA assessment). In conclusion, neither systematic nor abandoned, the place of carotid revascularization must necessarily be limited to the plaques at highest risk, leaving a large place for optimized medical treatment as first line management. An evaluation of the value of performing endarterectomy on plaques considered to be at high risk is currently underway in the ACTRIS and CREST 2 studies. These studies, along with the next result of ACST-2 trial, will provide us a more precise strategy in case of carotid stenosis.
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http://dx.doi.org/10.1093/eurheartj/suaa162DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7916422PMC
November 2020

International public awareness of peripheral artery disease.

Vasa 2021 07 1;50(4):294-300. Epub 2021 Mar 1.

Department of Cardiology, Dupuytren University Hospital, Limoges, France.

: Peripheral artery disease (PAD) of the lower limbs is a common condition with considerable global burden. Some country-specific studies suggest low levels of public awareness. To our knowledge public awareness of PAD has never been assessed simultaneously in several countries worldwide. : This was an international, general public, internet-based quantitative survey assessing vascular health and disease understanding. Questionnaires included 23 closed-ended multiple-choice, Likert scale and binary choice questions. Data were collected from 9,098 survey respondents from nine countries in Europe, North and Latin America during May-June 2018. : Overall, familiarity with PAD was low (57% of respondents were "not at all familiar", and 9% were "moderately" or "very familiar"). Knowledge about PAD health consequences was limited, with 55% of all respondents not being aware of limb consequences of PAD. There were disparities in PAD familiarity levels between countries; highest levels of self-reported awareness were in Germany and Poland where 13% reported to be "very" or "moderately" familiar with PAD, and lowest in Scandinavian countries (5%, 3% and 2% of respondents in Norway, Sweden and Denmark, respectively). There were disparities in awareness according to age. Respondents aged 25-34 were most familiar with PAD, with 12% stating that they were "moderately" or "very" familiar with the condition, whereas those aged 18-24 were the least familiar with PAD (7% "moderately" or "very" familiar with PAD). In the 45-54, 55-64 and 65+ age groups, 9% said they were "moderately" or "very" familiar with the term. There was no important gender-based difference in PAD familiarity. : On an international level, public self-reported PAD awareness is low, even though PAD is a common condition with considerable burden. Campaigns to increase PAD awareness are needed to reduce delays in diagnosis and to motivate people to control PAD risk factors.
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http://dx.doi.org/10.1024/0301-1526/a000945DOI Listing
July 2021

Gait changes after supervised exercise training in patients with symptomatic lower extremity peripheral artery disease.

Vasc Med 2021 Jun 11;26(3):259-266. Epub 2021 Feb 11.

Heart and Vessel Department, Division of Angiology, Lausanne University Hospital, Lausanne, Switzerland.

This study aimed to investigate the effects of supervised exercise training (SET) on walking performance and spatiotemporal gait changes in patients with symptomatic lower extremity peripheral artery disease (PAD). In this single-arm prospective nonrandomized cohort study, patients with Fontaine stage II PAD following a 3-month SET program were included. Before and after SET, a constant-load treadmill test was performed to determine the pain-free and maximal walking distances (PFWD and MWD, respectively). During this test, spatiotemporal gait parameters were assessed. The ankle-brachial index (ABI) and toe-brachial index (TBI) were also measured. Twenty-seven patients with PAD (64.0 ± 1.9 y, 74% men) were included. Following SET, the PFWD (+68%; = 0.001) and MWD (+79%; ⩽ 0.001) significantly increased. The ABI and TBI did not change significantly. Following SET, the stride duration, stride frequency, stride length, and double support phase duration did not change significantly. In contrast, subphases of stance showed significant changes: the loading response (+8%; = 0.03) and foot-flat (+2%; = 0.01) phases were significantly longer, whereas the push-off phase (-7%; = 0.002) was significantly shorter. A significant positive correlation was found between changes in the foot-flat phase and changes in PFWD ( = 0.43, = 0.03). A significant negative correlation was found between changes in the push-off phase and changes in PFWD ( = -0.39, = 0.05). No significant correlations were found between changes in relative durations of the subphases of stance and MWD. These results indicate that changes in temporal gait parameters during the foot contact phase potentially constitute an underlying mechanism of delayed claudication distance in patients with symptomatic PAD.
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http://dx.doi.org/10.1177/1358863X20984831DOI Listing
June 2021

Prognostic Impact of Obstructive Sleep Apnea in Patients Presenting with Acute Symptomatic Pulmonary Embolism.

Thromb Haemost 2021 Jun 30;121(6):808-815. Epub 2020 Dec 30.

CIBER Enfermedades Respiratorias (CIBERES), Madrid, Spain.

Background:  In patients with pulmonary embolism (PE), there is a lack of comprehensive data on the prevalence and prognostic significance of pre-existing obstructive sleep apnea (OSA).

Methods:  In this study of patients with PE from the Registro Informatizado de la Enfermedad TromboEmbólica (RIETE) registry, we assessed the prevalence of OSA, and the association between pre-existing OSA and the outcomes of all-cause mortality, PE-related mortality, recurrences, and major bleeding over 30 days after initiation of PE treatment. Additionally, we also examined rates of outcomes within 90 days and 1 year following the diagnosis of PE.

Results:  Of 4,153 patients diagnosed with PE, 241 (5.8%; 95% confidence interval [CI]: 5.1-6.6%) had pre-existing OSA. Overall, 166 (4.0%; 95% CI: 3.4-4.6%) died during the first 30 days of follow-up. In multivariable analysis, the OSA syndrome was not a significant predictor of death from any cause (odds ratio [OR]: 1.5; 95% CI: 0.8-2.9;  = 0.19). However, patients with pre-existing OSA had an increased PE-specific mortality (adjusted OR: 3.0; 95% CI: 1.3-6.8;  = 0.01) compared with those without OSA. OSA was not significantly associated with 30-day recurrent venous thromboembolism (adjusted OR: 0.6; 95% CI: 0.1-4.7;  = 0.65) or major bleeds (adjusted OR: 1.0; 95% CI: 0.4-2.2;  = 1.0). Findings were similar at 90-day and 1-year follow-ups.

Conclusion:  In patients presenting with PE, pre-existing OSA is relatively infrequent. Patients with OSA were at increased risk of PE-related mortality when compared with those without OSA.
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http://dx.doi.org/10.1055/s-0040-1721506DOI Listing
June 2021
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