Symptomatic Upper Extremity Peripheral Artery Disease is Associated With Poor Outcomes and a Broad Spectrum of Etiologies.

The symptomatic upper extremity peripheral artery disease (sUE-PAD) is poorly studied compared with the lower extremity peripheral artery disease (LE-PAD). We aimed to describe sUE-PAD etiologies and outcomes at 2 years. From an observational survey conducted in two French tertiary hospitals, demographic characteristics, etiology, treatment, and outcomes during follow-up were collected on patients with ICD-10 I74.2 code (arterial thrombosis of the upper limbs). We identified 181 patients (53% male, 55 ± 17 years) with hypothenar hammer syndrome (13.8%), cardioembolism (13.3%), atheroma (12.7%), or connective tissue disease (10.5%). No etiology could be found for 16.0% of them. The amputation rate was 13.3%, and lasting symptoms remained at 21.3%. During follow-up, atrial fibrillation occurred in 1 patient and cancer in 4. At 2 years, 59 patients were lost to follow-up, 110 patients were alive, and 12 patients had died. Age and cancer were associated with death. sUE-PAD is not benign, with 20% impaired upper extremity outcome and 10% overall mortality at 2 years. Less frequent than LE-PAD, sUE-PAD presents different characteristics: more women, younger age, and a broad spectrum of etiologies. sUE-PAD requires thorough etiological assessment and is considered to be associated with a severe overall prognosis.

Determinants of ventricular arrhythmias in sickle cell anemia: toward better prevention of sudden cardiac death.

Sudden death is 1 of the leading causes of death in adults with sickle cell anemia (SCA) but its etiology remains mostly unknown. Ventricular arrhythmia (VA) carries an increased risk of sudden death; however, its prevalence and determinants in SCA are poorly studied. This study aimed to identify the prevalence and predictors of VA in patients with SCA. From 2019 to 2022, 100 patients with SCA were referred to the physiology department to specifically analyze cardiac function and prospectively included in the DREPACOEUR registry. They underwent a 24-hour electrocardiogram monitoring (24h-Holter), transthoracic echocardiography, and laboratory tests on the same day. The primary end point was the occurrence of VA, defined as sustained or nonsustained ventricular tachycardia (VT), >500 premature ventricular contractions (PVCs) on 24h-Holter, or a recent history of VT ablation. The mean patient age was 46 ± 13 years, and 48% of the patients were male. Overall, VA was observed in 22 (22%) patients. Male sex (81% vs 34%; P = .02), impaired global longitudinal strain (GLS): -16% ± 1.9% vs -18.3% ± 2.7%; P = .02), and decreased platelet count (226 ± 96 giga per liter [G/L] vs 316 ± 130 G/L) were independently associated with VA. GLS correlated with PVC load every 24 hours (r = 0.39; P < .001) and a cutoff of -17.5% could predict VA with a sensitivity of 82% and a specificity of 63%. VAs are common in patients with SCA, especially in men. This pilot study uncovered GLS as a valuable parameter for improving rhythmic risk stratification.

Contribution of fetal microchimeric cells to maternal wound healing in sickle cell ulcers.

Leg ulcers are a major complication of sickle cell disease (SCD). They are particularly challenging to treat and innovative therapies are needed. We previously showed that the healing of SCD ulcers is delayed because of decreased angiogenesis. During pregnancy, fetal microchimeric cells (FMC) transferred to the mother are recruited to maternal wounds and improve angiogenesis. After delivery, FMC persist in maternal bone marrow for decades. Here, we investigated whether fetal cells could also improve SCD ulcers in the post-partum setting. We found that skin healing was similarly improved in post-partum mice and in pregnant mice, through increased proliferation and angiogenesis. In a SCD mouse model that recapitulates refractory SCD ulcers, we showed that the ulcers of post-partum SCD mice healed more quickly than those of virgin mice. This was associated with the recruitment of fetal cells in maternal wounds where they harbored markers of leukocytes and endothelial cells. In a retrospective cohort of SCD patients, using several parameters we found that SCD women who had ever had a baby had less of a burden related to leg ulcers compared to nulliparous women. Taken together, these results indicate that healing capacities of FMC are maintained long after delivery and may be exploited to promote wound healing in post-partum SCD patients.

Thromboprophylaxis Reduced Venous Thromboembolism in Sickle Cell Patients with Central Venous Access Devices: A Retrospective Cohort Study.

Sickle cell disease (SCD) induces a chronic prothrombotic state. Central venous access devices (CVADs) are commonly used for chronic transfusions and iron chelation in this population. CVADs are an additional venous thromboembolism (VTE) risk factor. The role of thromboprophylaxis in this setting is uncertain. The objectives are: (1) to determine whether thromboprophylaxis reduces VTE risk in SCD patients with CVAD and (2) to explore characteristics associated with VTE risk. We identified adults with SCD and CVAD intended for chronic use (≥3 months) at two comprehensive SCD centers. Thromboprophylaxis presence; type; intensity; and patient-, catheter-, and treatment-related VTE risk factors were recorded. Among 949 patients, 49 had a CVAD (25 without and 24 with VTE prophylaxis). Thromboprophylaxis type and intensity varied widely. Patients without thromboprophylaxis had higher VTE rates (rate ratio (RR) = 4.0 (95% confidence interval: 1.2−12.6), p = 0.02). Hydroxyurea was associated with lower VTE rates (RR = 20.5 (6.4−65.3), p < 0.001). PICC lines and Vortex and Xcela Power implantable devices were associated with higher rates compared with Port-a-Cath (RR = 5.8 (1.3−25.9), p = 0.02, and RR = 58.2 (15.0−225.0), p < 0.001, respectively). Thromboprophylaxis, hydroxyurea, and CVAD subtype were independently associated with VTE. The potentially protective role of thromboprophylaxis and hydroxyurea for VTE prevention in patients with SCD and CVAD merits further exploration.

Cardiovascular phenotypes predict clinical outcomes in sickle cell disease: An echocardiography-based cluster analysis.

This study sought to link cardiac phenotypes in homozygous Sickle Cell Disease (SCD) patients with clinical profiles and outcomes using cluster analysis. We analyzed data of 379 patients included in the French Etendard Cohort. A cluster analyses was performed based on echocardiographic variables, and the association between clusters, clinical profiles and outcomes was assessed. Three clusters were identified. Cluster 1 (n = 123) patients had the lowest cardiac output, mild left cardiac cavities remodeling, mild diastolic dysfunction, and higher tricuspid regurgitation velocity (TRV). They were predominantly female and displayed the most altered functional limitation. Cluster 2 (n = 102) patients had the highest cardiac output and the most remodeled cardiac cavities. Diastolic function and TRV were similar to cluster 1. These patients had a higher blood pressure and a severe hemolytic anemia. Cluster 3 (n = 154) patients had mild left cardiac cavities remodeling, normal diastolic function and lowest TRV values. They were younger with the highest hemoglobin value. Right heart catheterization was performed in 94 patients. Cluster 1 (n = 33) included the majority of pre-capillary PH whilst cluster 2 (n = 34) included post-capillary PH. No PH was found in cluster 3 (n = 27). After a follow-up of 11.4 ± 2 years, death occurred in 41 patients (11%). Cluster 2 patients had the worst prognosis with a 19% mortality rate versus 12% in cluster 1 and 5% in cluster 3 (p log-rank = 0.003). Cluster analysis of echocardiography variables identified three hemodynamic and clinical phenotypes among SCD patients, each predicting a different prognosis.

Clinical spectrum of ischaemic arterial diseases associated with COVID-19: a series of four illustrative cases.

BACKGROUND: Severe coronavirus-induced disease 2019 (COVID-19) leads to acute respiratory distress syndrome with an increased risk of venous thrombo-embolic events. To a much lesser extent, arterial thrombo-embolic events have also been reported in this setting. CASE SUMMARY: Here, we describe four different cases of COVID-19 infection with ischaemic arterial events, such as a myocardial infarction with high thrombus load, ischaemic stroke on spontaneous thrombosis of the aortic valve, floating thrombus with mesenteric, splenic and renal infarction, and acute limb ischaemia. DISCUSSION: Cardiovascular risk factors such as hypertension, obesity, and diabetes are comorbidities most frequently found in patients with a severe COVID-19 infection and are associated with a higher death rate. Our goal is to provide an overview of the clinical spectrum of ischaemic arterial events that may either reveal or complicate COVID-19. Several suspected pathophysiological mechanisms could explain the association between cardiovascular events and COVID-19 (role of systemic inflammatory response syndrome, endothelial dysfunction, activation of coagulation cascade leading to a hypercoagulability state, virus-induced secondary antiphospholipid syndrome). We need additional studies of larger size, to estimate the incidence of these arterial events and to assess the efficacy of anticoagulation therapy.

Diffuse alveolar hemorrhage after gadolinium injection during a MRI.

Gadolinium is a frequently used contrast product for MRI exam. It is well known to be less immuno-reactive than iodine used in tomodensitometry but is safety is not completely exempt of secondary effect. Here we report one case of acute interstitial pulmonary toxicity due to gadolinium. After quick elimination of others possible diagnosis and broncho-alveolar lavage we establish the link between acute intra-alveolar hemorrhage and gadolinium injection.

Immune response in Takayasu arteritis.

Takayasu arteritis (TAK) is a vasculitis of the large arteries. The arterial wall, target of the immune reaction, is composed of vascular dendritic cells, endothelial cells, vascular smooth muscle cells and fibroblasts, which engage in an interaction with T cells and macrophages to, ultimately, cause luminal stenosis or aneurysmal wall damage of the vessel. A multitude of cytokines have been identified to increase in case of TAK and to be linked to disease activity. A better understanding of the physiopathological pathways and mechanisms involved, might enable a more tailored therapeutic approach in TAK.