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Summary: The TOPASE study was set up to evaluate the outcomes of chronic myeloid leukaemia [CML] patients treated with ponatinib (PON) in a real‐world setting in France. One hundred and twenty CML patients, 105 in chronic phase (CP), 8 in accelerated phase (AP) and 7 in blastic phase (BP) were included. Fifty‐one (49%) of the CP‐CML patients were in third line of treatment. The trigger for PON initiation in CP‐CML was 'poor response' in 67 patients, 'poor tolerance' in 28 patients and 'response enhancement' in seven patients. The median dose at initiation was 30 mg/day [Q1; Q3 = 15; 30] in CP‐CML and 45 mg/day [Q1; Q3 = 30; 45] in AP/BP‐CML. Of 98 CP‐CML evaluable patients, 72 (73.5%) were considered as responders (MMR) at one time point at least once, especially for those in second line of treatment and/or presenting a T315I mutation. Ninety‐six of 120 (80%) patients reported at least one adverse event. An arterial occlusive event (AOE) was reported in 11 patients (9.2%). Thus, these real‐life data confirm the potency of ponatinib in resistant or intolerant patients with an acceptable safety profile in non‐selected patients. NCT number: NCT04048564. [ABSTRACT FROM AUTHOR]

Use of sulphur hexafluoride microbubbles (MB) with ultrasound can provide arterial wall enhancement. The use of ultrafast imaging with MB super-localization offers the possibility of ultrasound localization microscopy (ULM) and thus a visualization of in vivo carotid vasa vasorum. We aim to perform in vivo Vasa vasorum imaging in the carotid wall in Takayasu's arteritis and to provide a correlation with the disease's activity. Patients with Takayasu arteritis were consecutively included in the national referral centre. Assessment of activity was performed by NIH activity index, with measurement of biological inflammation, morphological evaluation by computed tomography (CT) angiography, and 18-fluorodeoxyglucose CT scan. Ultrafast ultrasound imaging was performed with a 7 MHz central frequency linear probe. A dedicated contrast imaging sequence (plane waves with 8 angles, frame rate 500 Hz, voltage 8 V, duration of 8 s), coupled with the intravenous injection of sulphur hexafluoride MB allow us to store the raw radio frequency data of the MBpassage. After a pre-processing step to accumulate frames properly including a frames selection and a movement correction, the MB were localized then tracked, allowing reconstruction of the vasa vasorum. The inflammation was quantified through MB tracked and normalized for inter acquisition comparison. Sixteen patients were included. 5 patients (median age 35.8 [24.5–46.0] years, 3 women) had active disease and 11 patients (37.2 [31.7–47.3] years, 9 women) had quiescent disease. The passage of MB allowed the visualisation of microvessels within the arterial wall for active cases (Fig. 1A). The number of MB detected per second in the wall was 118 [80–169] for active cases vs. 13 [10–15] for quiescent cases (P = 0.0005) (Fig. 1B). The sum of the length of the tracks, i.e., the MB path per second of acquisition, was computed with a significant difference between the two groups (43.0 mm [32.9–65.5] in active TA vs. 4.6 mm [2.9–5.4]). ULM allows visualization of microvessels within the carotid wall, with significantly greater MB passage in active Takayasu arteritis. ULM provides for the first time a precise visualization in vivo of the vasa vasorum and gives access to quantification of the vascularity of the arterial wall. [ABSTRACT FROM AUTHOR]

Coronavirus disease 2019 (COVID-19) use Angiotensin-Converting Enzyme 2 (ACE-2) as a viral gateway and could have interactions with the RAA system. Other studies have found kalemia abnormalities associated with severe forms of COVID-19.Our goal was to assess the prognosis value of kalemia in severe COVID-19 hospitalized population. We analyzed data from a monocentric prospective observational cohort that included 65 patients PCR-confirmed positive for COVID-19 who were admitted at HEGP in Paris, between 15 to 21 March, 2020. The study aimed to determine the relationship between baseline kalemia and the primary composite outcome defined as admission to an intensive care unit (ICU) or death. Baseline kalemia was defined as the presence of a kalemia under 3.8 mmol/L within 10 days of the first symptom onset. We included 65 patients with PCR COVID-19 positive test. Median age was 65 years old and 66.2% were male. Baseline kalemia under 3.8 mmol/l occurred in 31 patients (48%) including 11 patients (35.5%) who were hospitalized in ICU and 1 patient (3.2%) who died before ICU admission. In the primary end-point analysis based on multiple imputations for missing data, the adjusted hazard ratios for admission to ICU or death were 3.52 [95%(CI), 1.12 to 11.04] among patients who presented a kalemia under 3.8 mmol/L within 10 days of the first symptom onset. Moreover, we did find an adjusted association between baseline kalemia and the minimum hemoglobin level presented by the patients during the hospital stay (odds ratio, 0.80; 95% CI, 0.64 to 0.99) (Fig. 1). Our study suggests that the presence of a kalemia under 3.8 mmol/L within 10 days of the first symptom onset might be associated with an increased risk of intensive care unit or death, and the minimum hemoglobin level presented by the patients during the hospital stay. Future intervention studies aimed for correcting this hypokalemia with ARBs to improve prognosis are ongoing. [ABSTRACT FROM AUTHOR]

Post thrombotic syndrome is a frequent complication of deep venous thrombosis, associated with high morbidity. Treatments currently available are invasive. Pulsed cavitational ultrasound therapy (PCUT) is a new technique to destroy remotely soft tissue. We demonstrated that PCUT was able to recanalize non-invasively in in-vitro model of human blood clot. We aim to test the safety and efficacy of venous recanalization by non-invasive PCUT in vivo swine model of acute venous thrombosis. All the experiments were performed on White large X Landrace swine. We induced an acute femoral deep venous thrombosis by using endovascular approach combined with local injection of thrombin. A 3 cm length occlusive thrombosis was obtained after 2 hours. Swine were divided in three groups: one with PCUT without follow-up (n = 11), one with PCUT and follow-up at 14 days (n = 8), and a control group also followed for 14 days (n = 5). Acutely and during follow up all swine received curative anticoagulation. To achieve PCUT, a 2.25 MHz transducer (Imasonic©) centered by a linear probe was used and cavitation was obtained in the centre of the vein. Effectiveness of recanalization was evaluated by echo-Doppler and phlebography. Safety was assessed by Doppler ultrasound and by histological analysis of vein, artery and lungs. Among the 24 swine, we obtained 22 occlusive venous thromboses and 2 partials. The median length of the thrombus was 26 ± 4.4 mm. Acutely, thrombosis recanalization was obtained among the 19 swine with PCUT with median treatment duration of 33 min. After a 14-day follow-up, 75% of recanalisation remains permeable vs. 0% of vein permeable in the no therapy group (P = 0.008). Residual diameter was 2.6 ± 1.2 mm, 50% of the venous diameter. No embolism or pulmonary infarction was observed in all pigs (Fig. 1). We have demonstrated in vivo the safety and the efficacy of PCUT for non-invasive venous recanalization, persistent after 2 weeks. [ABSTRACT FROM AUTHOR]

Ultrafast Ultrasound Imaging (UUI) provides an estimation of carotid plaque stiffness by shear wave elastography (SWE) and the quantification of wall shear stress (WSS) by ultrafast Doppler. We aimed to evaluate the combined criteria of plaque stiffness and WSS applied on the plaque as potential biomarkers of plaque vulnerability assessed by histology. We included patients for whom carotid endarterectomy had been decided by a multidisciplinary team. UUI was performed within 48 hours before surgery, and acquisitions were obtained on a carotid longitudinal view. After endarterectomy, gross examination and histological analysis were performed on each removed plaque. Forty-six plaques with SWE data and 29 with WSS data were analysed. Histological analysis revealed 29 vulnerable and 17 stable plaques. Gray Scale Median analysis by B mode, mean and standard deviation of stiffness by SWE did not differ between vulnerable and stable plaques. SWE analysis revealed that the percentage of stiffness range of [3–5] m/s was significantly increased in vulnerable plaques (P = 0.048). WSS alone showed no difference between stable and vulnerable plaques regardless of the segment of the plaque which was analysed. A multiparametric score using maximal WSS at the peak of the plaque associated with SWE texture analysis parameters was calculated by stepwise regression, leading to a score with a sensitivity of 80% and a specificity of 78%. Area under the Receiver Operating Characteristics curve was 0.85. A multiparameter scoring system including plaque stiffness and flow analysis using UUI allows to effectively identify histologically vulnerable carotid plaques. [ABSTRACT FROM AUTHOR]

To develop specific aortic sequences in ultrafast ultrasound imaging (UF) to provide access to the aortic MRSD. We used a phased array probe (Supersonic Imagine©) and dedicated sequences at 2000 frames/s developed in the laboratory. Data were analyzed with a created interface (Fig. 1) to automatically track the anterior and posterior aortic walls over the cardiac cycle. Tissue Doppler allowed a precise estimation of the movement of each wall and the fine variation of the aortic diameter. MRSD was the maximum of the derivative of the diameter curve over time. To assess the feasibility of this new technique, 24 patients (10 BAV patients and 14 controls) were consecutively included in a reference center for BAV. The ascending aorta was evaluated at the sinus of Valsalva, the tubular aorta and the aortic arch. UF acquisitions and the dedicated interface allow to track the aortic diameter and to calculate the MRSD for the 10 BAV patients and 14 controls (mean age of 45.8 vs. 40.7 years, P = 0.464). As expected, a lower aortic strain was found at each aortic segment in case of BAV (Table 1). MRSD values followed the same trend, as observed with MRI. As already demonstrated, the sinus of Valsalva has a high stiffness in case of BAV and we found a significant difference in MRSD with UF imaging (1.05 s-1 [0.73–1.19] vs. 1.51 s-1 [1.28–1.99], P = 0.023) (Fig. 1). Aortic evaluation with UF by MRSD is feasible and can get access potentially to the evaluation of to the segmental ascending aortic remodeling associated to BAV using easy to use ultrasound based technique. [ABSTRACT FROM AUTHOR]

Lower extremity-peripheral artery disease (LE-PAD) is associated with an increased risk of cardiovascular death (CV death) and represents a heavy burden in cardiovascular morbidity and mortality. The COMPASS trial demonstrated an interest in giving rivaroxaban 2.5 mg twice-daily plus acetylsalicylic acid for the prevention of atherothrombotic events in patients with high risk PAD or coronary artery disease. COPART (COhorte de Patients ARTériopathes) is the only French registry of consecutive hospitalized patients admitted for LE-PAD management, with a one-yean follow-up. The aim of the analysis was to estimate the percentage of patients with LE-PAD eligible to a treatment with rivaroxaban 2.5 mg twice daily plus a low dose of ASA once daily and describe their characteristics and prognosis. Among 2,513 patients included in the COPART registry 1,472 (58.6%, CI 95 56.7%–60.5%] fulfilled the COMPASS criteria. The main reason for non -inclusion in the analysis was the need of double antiplatelet or anticoagulant therapy. Mean age was 70.5 years in the whole sample (69.3 in COMPASS-like patients), 75.1% of the patients were men (73.9% of COMPASS patients), 36.7% had a previous history of CAD (32.9% in COMPASS-like patients), 37.5% had renal failure (33.7% in COMPASS-like patients), 70% presented with Rutherford IV-V-VI (66% of COMPASS-like), 37.2% presented with hemodynamically proven critical limb ischemia (34.1% of COMPASS-like patients). Incidence rates of all cause death were 18.2 in the whole sample and 12.1/100 person-years among COMPASS-like patients. A total of 1,092 patients (49.8%) had at least one complication during the one-year follow-up period (543, 44.4%, COMPASS-like patients) (Fig. 1). Male gender, diabetes, cardiac failure, anemia at index hospitalization, and severe stage PAD (rest pain, ulcer or gangrene, acute ischemia) were associated with an increased one-year risk of complication in both groups. [ABSTRACT FROM AUTHOR]

Objective Patients with mutant gene encoding type III collagen experience arterial ruptures, called vascular Ehlers-Danlos syndrome (vEDS). Our goal was to assess the aortic mechanical behaviour by measuring the pulse wave velocity (PWV) at different blood pressure levels in the new model of vEDS: Knock-In Gly183Arg mice (col3KI-mice) presenting a qualitative default in type III collagen. Methods We compared Black-6 col3KI-mice to their wild type (WT) littermates. An age of 12–20 weeks was chosen, due to high early mortality rate in col3KI-mice. Doses of phenylephrine (0.01–700 μg/kg) were used to increase the blood pressure, recorded with a carotid catheter in anesthetized mice. Abdominal aortic PWV was measured by Ultrafast ultrasound imaging (2800 frames/s) with a 15 MHz probe. PWV was measured at the waveform's foot (PWV1), generated at the minimal diastolic blood pressure (DBP) and at the dicrotic notch (PWV2), at the systolic blood pressure (SBP). To evaluate the arterial intrinsic properties, we reported each PWV to their corresponding arterial pressure: PWV1/DBP and PWV2/SBP. Difference of these two PWV (Delta-PWV), reported to the pulse pressure (PP) as Delta-PWV/PP, is related to the arterial stiffening in the cardiac cycle. Mann-Whitney test was used for comparisons. Results 8 col3KI-mice (5 females, 3 males) were compared to 23 WT (12 females, 11 males) of comparable age (124 ± 28 days) and weight (25.7 ± 4.3 g). PWV1/DBP was lower in col3KI-mice (2.73 cm.s −1 .mmHg −1 [2.61–2.85] vs. 2.99 [2.89–3.09]; P = 0.027). This was also the case at the systolic level, with lower PWV2/SBP (2.86 [2.75–2.98] vs. 3.61 [3.48–3.74]; P < 10 −15 ). Delta-PWV/PP (cm.s −1 .mmHg −1 ) was lower in col3KI mice (4.38 [3.56–5.18] vs. 8.12 [6.98–9.27]; P < 10 −6 ) showing a lack of stiffening during the cardiac cycle ( Fig. 1 ). Conclusion In col3KI-mice, arterial rupture may be underlain by the lack of arterial stiffening due to the absence of type III collagen recruitment when pressure rises. [ABSTRACT FROM AUTHOR]

Carotid plaque vulnerability assessment is an important factor in guiding the decision to perform carotid endarterectomy in case of asymptomatic stenosis. Ultrafast Ultrasound Imaging (UUI) offers the possibility of evaluating local flow velocities over an entire 2D image, allowing access to measure the wall shear stress (WSS). Our objective was to evaluate the feasibility of WSS measurement in a prospective series of patients with carotid stenosis. We used a linear probe (7.5 MHz, SuperSonic Imagine©). UUIacquisitions last 600 ms with 3 tilted plane waves for an effective frame rate of 5000 Hz. We evaluated the flow velocity in 5 areas of the carotid wall: common carotid artery (1), plaque ascent (2), peak (3), descent (4), and internal carotid artery (5) (Figure 1). WSS was computed with the vector field speed. Shear stress measurement method was validated using a laminar flow phantom with laminar flow. Good correlation was found between in vitro measurement and the theoretical WSS values (R2 = 0.95; P < 0.001). 25 patients were included (mean age: 72 ± 5 years), with a mean percentage of stenosis of 75 ± 12% (NASCET). The maximum WSS value over one cardiac cycle follows the shape of the plaque with a progressive increase to a maximum value at the peak (2.12 ± 1.27 Pa). The post-stenotic descent zone has the lowest shear stress (0.57 ± 0.39 Pa), lower than the WSS values in the healthy zone (1.02 ± 0.36 Pa for the common carotid and 0.68 ± 0.39 Pa for the internal carotid artery) (Figure 1). This method allowed the local and direct evaluation of the plaque's wall shear stress. Unlike the global evaluation of speed using conventional Doppler, these measurements make it possible to better characterize the haemodynamic conditions to better identify areas of vulnerability. [ABSTRACT FROM AUTHOR]

The fifth author's name was incorrectly published as "M. Messas". The correct name is "E. Messas". The original article has been corrected. [ABSTRACT FROM AUTHOR]

Objective Persistent occlusion following venous thrombosis is associated with an increased risk of post-thrombotic syndrome. Early venous recanalization may prevent this complication. Ultrasonic histotripsy fractionates soft tissue through a cavitation cloud generated by an external transducer. We aimed at testing this technique as a drug-free thrombolysis on recent in vitro clots. Methods Venous thrombosis conditions were reproduced in vitro, using human blood clotting by stasis in silicone tubes (6 mm internal diameter, close to the femoral vein), in a 37 °C water-bath, then mounted on a saline solution at a 25 mmHg constant pressure. The ultrasound device was composed of dual 2.25 MHz transducers centred by a 7-MHz linear probe. A single cavitation cloud was generated at a 3.2-cm depth from the device. Thrombotripsy was performed by longitudinal passages along of the whole thrombus at 3 pre-specified speeds (1; 2; 3 mm/s). Restored outflow was assessed every 3 passages. Results 24 occlusive successive thrombi of 2.5 cm mean's length were evaluated. Flow restoration was systematically obtained by the succession of 9 passages. An efficient flow restoration was carried out in 6 min maximum. Regardless from the device's speed, an average time of 76 ± 17 s was necessary to obtain a 70% flow recovery ( Fig. 1 ). A speed of 1 mm.s −1 allowed an efficient recanalization (80% ± 7%) after only 3 passages, corresponding to a treatment's duration of 1.5 min with the lowest variability. The cavitation drilled a circular channel of 1.7 mm mean diameter throughout the clot with a 1.5-mm thick residual thrombus coating the tube. Debris analysis found no debris > 200 μm with 92% of debris < 10 μm. Conclusion Our dual transducers thrombotripsy device performed a fast recanalization of whole-blood thrombus without any parietal alteration or bulky debris formation. This new technology opens the field to a drug-free and non-invasive thrombolysis. [ABSTRACT FROM AUTHOR]

Background Vascular Elhers-Danlos syndrome (vEDS) is a genetic vascular disease, affecting the production of the collagen type III, a component of the arterial wall, but also in the mitral valve (MV). Some small families studies suggest an association between vEDS and mitral valve prolapse [MVP] but a complete evaluation of MV phenotype on vEDS cohort was never performed. Purpose To describe the MV phenotype in a population of vEDS. Methods A total of 45 patients with vEDS, with characterized mutation of the COL3A1 gene, were included in a prospective single-center study and assessed by echocardiography. Results Among the 45 patients, no MVP was found. MV floppy was observed in 6 patients (13%) but the mean MV thickness of 2.7 ± 0.1 mm for all the group was not above normal (normal values [NV] < 3 mm). MV billowing was observed in 2 patients (4%).35 patients (78%) had mitral insufficiency but none were more than mild (trace 26 [58%] and mild 9 [20%]) and there was no mitral stenosis (mean mitral gradient = 1.31 ± 1 mmHg). Anterior leaflet length was 24 ± 0.5 mm (vs. NV = 22–23 mm), posterior leaflet length was 13.7 ± 0.3 mm ( NV = 12–13 mm) and strut chordae length was 20.4 ± 1 mm ( NV < 20 mm). Mitral annulus (MA) diameter was 33.1 ± 0.6 mm in the parasternal long axis view (PSLAV) ( NV = 31.5 ± 0.5 mm) and 33.7 ± 0.6 mm in apical 4 chambers view (A4CV) ( NV = 30.5 ± 0.4 mm) for men. In women, MA diameter was 30.4 ± 0.5 mm in PSLAV ( NV = 28.3 ± 0.4 mm) and 29.5 ± 0.6 mm in A4CV ( NV = 27.7 ± 0.3 mm). The ratio between MA diameter and the mitral anterior leaflet height was calculated at 1.3 ± 0.03 ( NV < 1.3). Two case of ruptured mitral chordae with a previously normal echocardiographic MV were observed. Conclusion Through a single cohort of vEDS, there was no evidence of MVP despite cases of chordal ruptured. MA and mitral leaflets were larger than the classical published value. More studies are needed to better characterized the biomecanic of the MV apparatus explaining the rare occurrence of MV chordae rupture. [ABSTRACT FROM AUTHOR]

Objective Bicuspid aortic valve (BAV) is associated with high incidence of ascending aortic aneurysm. In BAV sporadic form, changes in outflow's hemodynamic secondary to the valvular morphotype are said to play a prominent role in the aortic dilatation. We aimed at comparing the different ascending aorta segment diameters according to the morphotype and the function of the BAV. Methods We evaluated 174 patients with sporadic BAV by transthoracic echocardiography. The valvular function was defined as either Aortic Insufficiency (AI) if Grade ≥ 2 and aortic Stenosis (AS) if mean gradient > 20 mmHg. Aortic diameters were measured at the Valsalva sinus, tubular ascending aorta and at the aortic arch. Kruskal-Wallis, Mann–Whitney and Spearman tests were used for comparisons. Results Among the non-operated patients, Sievers’ morphotype was type 1LR for 63%, type 1NR for 18%, and other types counted for 19%. The Valsalva sinus diameter did not differ according to the Sievers’ type ( P = 0.78). The type 1LR type compared to the type1NR appeared to have a wider tubular aorta, but not significantly (42.3 ± 8.5 vs. 36.4 ± 7.3 mm; P = 0.06). Aortic valve function was distributed as follows: AI: 39%, AS: 20%, Both: 9%, Normal: 32%. Comparison of the different valve dysfunctions revealed a difference at the Valsalva ( P < 10–4) and the tubular aorta ( P = 0.001) but not at the aortic arch level ( P = 0.62). AI was highly associated with an increase of the aortic diameters of any segment, excepting for the arch. In addition, aortic diameters increased with age in case of AI (Valsalva: r = 0.28; P = 0.02; Tubular aorta: r = 0.27; P = 0.02) and not in case of AS ( r = –0.06; P = 0.73 and r = –0.03; P = 0.84). Conclusion Our results showed the tremendous role of AI in the aortic dilation of all segments except the arch. However no influence of BAV morphotype was noticed on aortic diameters. Our results give rise to the relatively limited influence of the valvular morphology in the development of aortic dilation. [ABSTRACT FROM AUTHOR]