P4490Safety and feasibility of non invasive transthoracic pulsed cavitational ultrasound therapy (PCUT) on a swine aortic valve model

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
E Messas ◽  
M Remond ◽  
G Goudot ◽  
R Penot ◽  
D Ladarre ◽  
...  
Keyword(s):  
Side Effects ◽  
Aortic Valve ◽  
High Power ◽  
Ultrasound Therapy ◽  
Antithrombotic Treatment ◽  
Invasive Approach ◽  
Non Invasive ◽  
Valve Model

Abstract Background Aortic valve stenosis is associated with age and comorbidities, which require exploring less invasive therapeutic approach to improve patient outcome. We previously demonstrated in vitro and in vivo that pulsed cavitational ultrasound therapy (PCUT) can improve calcified bioprosthesis stenosis by softening leaflets remotely. To apply this technique noninvasively we aim to test PCUT transthoracicalyin a swine model targeting aortic valve. Because calcified aortic valve model doesn't exist, we tested this technique on a normal valve. Objective Primary objective was to estimate the feasibility and safety of PCUT. Secondary objectiveswere to evaluate occurrence, severity and evolution of cardiovascular side effects during therapy and within follow-up period (30±5 days) with and without double antithrombotic treatment. Methods All the experiments were performed on normal aortic valves (n=19) of swine. The system was composed of a high-power multi-element transducer with electronic steering and 2D echocardiographic probe embedded in the center. Swine were divided in three groups: one with PCUT and no anti thrombotic treatment (n=10), a second with PCUT and one-month treatment of aspirin and clopidogrel (n=5) and third group sham (n=4). All groups were followed up after 30 days. Results The primary feasibility endpoint was successful in 100% of tests performed (n=16). A maximal amplitude of 70 MPa and −19 MPa respectively for positive and negative peak pressure was found at the focus point. Survival at 30 days was 100% and no life-threatening arrhythmia was recorded and no sustained ventricular arrhythmia (SVT >30 s) was noticed. For the secondary safety objectives,we recorded acutely, at the time of procedure, NSVT in 7 pigs which corresponded to a cumulated duration of 2.1 out of the 485.3 min of the total US delivery (0.4% of time). Mean cycle of NSVT was slow 428.9 ms in average (139.6 bpm). The interruption or decrease of power of US delivery allowed immediate cessation of cardiac arrhythmia in all cases. There was no evidence of damage to the valve and no observation of impairment of valvular function by echocardiography. Only one animal showed side effects (RV dilatation) and the RV returned to normal after cessation of the therapy with no sequelae at follow up. At follow up no significant findings biology disturbance or valve thrombosis was observed (creatinine, CK MB, hemoglobin, hematocrit, haptoglobin or red blood cell numbers). Antithrombotic treatment didn't demonstrate any advantage at follow up. Conclusion We demonstrated in vivo feasibility and safety of transthoracic PCUT targeting aortic valve without any serious adverse event and no significant histopathology damage. We hope that this first-time transthoracic delivery of very focused ultrasound at high power will pave the way to new non invasive approach of valve softening in case of human aortic valve calcified stenosis.

Abstract 17142: Long Term Results of Non-Invasive Ultrasound Therapy (NIUT) in Severe Symptomatic Aortic Valve Stenosis - First-in-Man

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Emmanuel Messas ◽  
Alexander Ijsselmuiden ◽  
Selina Vlieger ◽  
Peter den Heijer ◽  
Guillaume Goudot ◽  
...  
Keyword(s):  
Heart Failure ◽  
Aortic Valve ◽  
Aortic Stenosis ◽  
Pressure Gradient ◽  
Aortic Valve Stenosis ◽  
Long Term Results ◽  
Ultrasound Therapy ◽  
Non Invasive ◽  
Mean Pressure

Background: Not all patients with severe aortic valve stenosis are eligible for open-heart surgery or TAVR. CARDIAWAVE (Paris, France) has developed Valvosoft, a unique non-invasive ultrasound therapy device to treat aortic stenosis. The therapy aims to improve the opening of severely calcified aortic valves by cracking the calcium and reducing the stiffness in the aortic valve tissue by delivering transthoracically local shock waves on the valve leaflets. This study assesses the safety, feasibility and performance of this novel technique. Methods: This is a multi-center, prospective, first-in-man study designed to evaluate the safety and feasibility of the Valvosoft device. Ten patients with severe symptomatic calcific aortic stenosis and not eligible for SAVR/TAVR underwent a Valvosoft ultrasound therapy. Echocardiographic evaluation was performed by an independent core lab at baseline, discharge, and at 1, 3, 6 and 12 months along with clinical follow up. Results: Enrolled patients were advanced in age (84.1±6.5 yrs) with severe comorbidities (8 with heart failure, 5 with coronary heart disease and 5 with kidney failure). All had extensive aortic valve calcification with mean AVA of 0.61±0.17 cm2 and mean pressure gradient of 37.5±10.5 mmHg. At one-month follow-up, six patients had significantly improved their AVA with increase of 27.5% (p=0.03) and mean pressure gradient decrease of 23.2 % (p=0.025). These patients also received the highest dose and longest treatment duration. During one year follow up, 4 patients died due to progression of end stage heart failure not linked to the procedure and one patient had undergone a TAVR procedure. At 12 months, the five remaining patients has no device or procedure related major adverse events nor deterioration of neurological status. Echo, brain-MRI and clinical follow up will be presented. Conclusions: Non-invasive ultrasound therapy is feasible and safe in patients with severe aortic valve stenosis and can improve AVA and hemodynamic parameters. NIUT can be an important tool complementary to TAVI in treating patients with aortic valve stenosis.

scholarly journals Safety, feasibility and performance of Valvosoft non-invasive ultrasound therapy in patients with severe symptomatic calcific aortic valve stenosis. First-in-Man

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
E Messas ◽  
A Ijsselmuiden ◽  
G Goudot ◽  
S Vlieger ◽  
P Den Heijer ◽  
...  
Keyword(s):  
Aortic Valve ◽  
Pressure Gradient ◽  
Ultrasound Therapy ◽  
Funding Source ◽  
Non Invasive ◽  
Post Procedure ◽  
Mean Pressure ◽  
Valve Opening ◽  
The Mean

Abstract Objectives We recently developed a unique transthoracic non-invasive ultrasound therapy device called Valvosoft to treat aortic stenosis. The therapy consists in delivering trans-thoracically precisely focused and controlled short ultrasound pulses (<20μsec) at a high acoustic intensity to produce non-thermal mechanical tissue softening of the calcified aortic valve with the ultimate aim of improving the valve opening. Ultrasound imaging enables to follow valve movements in real-time and thus targets the ultrasound waves on the valve with great precision. After having validated this concept in pre-clinical studies, we aimed at applying this technique in human. The primary objectives were to assess the safety and feasibility of this novel technique along with its performance by evaluation of the valve leaflets mobility and valve opening area. Methods This is a multi-center, prospective, controlled first-in-man study. Ten patients with severe symptomatic calcific aortic stenosis and not eligible for SAVR/TAVR underwent a Valvosoft ultrasound therapy. The therapy consists of 6 sessions of ultrasound therapy. The Valvosoft transducer is applied on the patient's chest and coupled at its center with an echocardiography phased array probe to allow real-time control of the therapy (cavitation bubble detection). Preselection of the region of interest is performed by echo still frame before each session. Ultrasonic evaluation was performed by an independent core lab at baseline, discharge, 30-day and 3 month follow-up along with clinical follow up. Results Enrolled patients were advanced in age (84.1±6.5 yrs) with severe comorbidities (8 with heart failure, 5 with coronary heart disease and 5 with kidney failure). All had extensive aortic valve calcification (mean calcification volume of 687.28 mm3) with mean AVA of 0.61±0.17 cm2 and mean pressure gradient of 37.5±10.5 mmHg (6 patients had SV<35ml/m2). No adverse events were recorded during the procedures other than some benign ventricular extrasystoles. The mean treatment time was 52 minutes. At 3 months follow-up, one patient had died due to end stage heart failure not linked to the procedure (9 weeks post procedure) and another got finally TAVI (45 days post procedure). Of the other 8 patients, 6 experienced an improvement of their NYHA status. No device or procedure related major adverse events nor deterioration of neurological status were observed at 3 months follow-up. Of the 7 patients that had echo follow-up at 3 months (one patient refused to get echo evaluation), 5 increased the AVA (between 14% and 46%) and 4 patients decreased the mean pressure gradient (from 6% to 44%). No AI or EF deterioration occurred during follow up. Conclusion Non-invasive ultrasound therapy is feasible and safe in patients with severe aortic valve stenosis and is able to improve AVA and pressure gradient in some patient. Larger studies with longer follow up will need to be conducted. Funding Acknowledgement Type of funding source: Private grant(s) and/or Sponsorship. Main funding source(s): Cardiawave SA, Paris, France

Sutureless Aortic Valve Implantation through an Upper V-Type Ministernotomy: An Innovative Approach in High-Risk Patients

2013 ◽  
Vol 8 (1) ◽  
pp. 23-28 ◽  
Author(s):  
Giovanni Concistrè ◽  
Antonio Miceli ◽  
Francesca Chiaramonti ◽  
Pierandrea Farneti ◽  
Stefano Bevilacqua ◽  
...  
Keyword(s):  
High Risk ◽  
Aortic Valve ◽  
Minimally Invasive ◽  
Minimally Invasive Approach ◽  
Invasive Approach ◽  
High Risk Patients ◽  
Risk Patients ◽  
The Mean ◽  
Valve Implantation

Objective Aortic valve replacement in minimally invasive approach has shown to improve clinical outcomes even with a prolonged cardiopulmonary bypass and aortic cross-clamp (ACC) time. Sutureless aortic valve implantation may ideally shorten operative time. We describe our initial experience with the sutureless 3f Enable (Medtronic, Inc, ATS Medical, Minneapolis, MN USA) aortic bioprosthesis implanted in minimally invasive approach in high-risk patients. Methods Between May 2010 and May 2011, thirteen patients with severe aortic stenosis underwent aortic valve replacement with the 3f Enable bioprosthesis through an upper V-type ministernotomy interrupted at the second intercostal space. The mean ± SD age was 77 ± 3.9 years (range, 72–83 years), 10 patients were women, and the mean ± SD logistic EuroSCORE was 15% ± 13.5%. Echocardiography was performed preoperatively, at postoperative day 1, at discharge, and at follow-up. Clinical data, adverse events, and patient outcomes were recorded retrospectively. The median follow-up time was 4 months (interquartile range, 2–10 months). Results Most of the implanted valves were 21 mm in diameter (19–25 mm). The CPB and ACC times were 100.2 ± 25.3 and 66.4 ± 18.6 minutes. At short-term follow-up, the mean ± SD pressure gradient was 14 ± 4.9 mm Hg; one patient showed trivial paravalvular leakage. No patients died during hospital stay or at follow-up. Conclusions The 3f Enable sutureless bioprosthesis implanted in minimally invasive approach through an upper V-type ministernotomy is a feasible, safe, and reproducible procedure. Hemodynamic and clinical data are promising. This innovative approach might be considered as an alternative in high-risk patients. Reduction of CPB and ACC time is possible with increasing of experience and sutureless evolution of actual technology.

P6496Endovascular reconstruction from aortic valve to aortic arch by one-piece valved-fenestrated-bifurcated endografting in animal experiments

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
Z P Jing ◽  
J X Feng ◽  
X H Bao ◽  
T Li ◽  
Y Zhao ◽  
...  
Keyword(s):  
Aortic Valve ◽  
Aortic Arch ◽  
Aortic Root ◽  
Animal Experiments ◽  
Proximal Part ◽  
Minimal Invasive ◽  
Left Ventricular ◽  
Technical Success Rate

Abstract Aims The possibility of endovascular reconstruction of aortic valve, sinus of Valsalva, and ascending aorta by a minimal-invasive single endograft has not been proven in vivo. Combining our own long-term experiences from transcatheter aortic valve replacement (TAVR) and Thoracic Endovascular Repair (TEVAR) for ascending and arch dissection, we designed the special endo-graft: a novel one-piece valved-fenestrated-bifurcated endografting, and tried to endovascularly reconstruct the area from Left ventricular outflow tract to aortic arch in animal experiments. Methods and results For 20 healthy adult female pigs weighed between 62.3±2.2 kilograms, we did aortic compute tomography angiography (CTA) examinations and measured morphologic parameters of aortic root. Then we accordingly customized the valved-fenestrated-bifurcated endograft. The endograft was delivered through transapical access and endovascularly reconstructed the segment from aortic valve to proximal part of aortic arch. The overall technical success rate was 95% because of one case of delivery system failure. Instant transesophageal echography (TEE) and aortic CTA confirmed ideal position of the endograft, satisfactory function of aortic valve, and the patency of coronary arteries in all subjects. During follow-up, 12 subjects were sacrificed according to the plan and seven were followed up for 8.1±3.6 months. There was one unplanned death of cardiac infection (unplanned mortality: 5.3%). Follow-up re-examinations (aortic CTA, cardiac ultrasound, and electrocardiogram) found no adverse events. Among 12 sacrificed subjects, there was no evidence of fenestrations alignment lost and no myocardial ischemia according to the pathological analysis. Conclusion The novel one-piece valved-fenestrated-bifurcated endografting might be feasible for minimal-invasive reconstruction of aortic root in animal models, thus provided a prospect to simultaneously treat pathologies involving aortic valve and aortic root in endovascular way.

P2-468: In vivo follow-up of cerebral aging and side effects of anti-amyloid immunotherapies in the mouse lemur primate

2011 ◽  
Vol 7 ◽  
pp. S462-S463
Author(s):  
Nelly Joseph-Mathurin ◽  
Olène Dorieux ◽  
Audrey Kraska ◽  
Mathieu Santin ◽  
Stéphanie Trouche ◽  
...  
Keyword(s):  
Side Effects ◽  
Mouse Lemur

A single-step multi-level supramolecular system for cancer sonotheranostics

2019 ◽  
Vol 4 (1) ◽  
pp. 190-195 ◽  
Author(s):  
Huirong Lin ◽  
Shuang Li ◽  
Junqing Wang ◽  
Chengchao Chu ◽  
Yang Zhang ◽  
...  
Keyword(s):  
Self Assembly ◽  
Single Step ◽  
Supramolecular System ◽  
Therapeutic Effects ◽  
Invasive Approach ◽  
Non Invasive ◽  
Ionic Crosslinking ◽  
Critical Issues ◽  
Multi Level

A multi-level supramolecular system produced by single-step Fe3+-mediated ionic crosslinking self-assembly can overcome the critical issues of current sonodynamic therapy (SDT) and address the need to monitor therapeutic effects in vivo with a non-invasive approach.

IC-P-087: In vivo follow-up of cerebral aging and side effects of anti-amyloid immunotherapies in the mouse lemur primate

2011 ◽  
Vol 7 ◽  
pp. S44-S44
Author(s):  
Nelly Joseph-Mathurin ◽  
Olene Dorieux ◽  
Audrey Kraska ◽  
Mathieu Santin ◽  
Stéphanie Trouche ◽  
...  
Keyword(s):  
Side Effects ◽  
Mouse Lemur

scholarly journals Imaging of microglial activation in MS using PET: Research use and potential future clinical application

2016 ◽  
Vol 23 (4) ◽  
pp. 496-504 ◽  
Author(s):  
Laura Airas ◽  
Eero Rissanen ◽  
Juha Rinne
Keyword(s):  
Complex Disease ◽  
Treatment Options ◽  
Quantitative Information ◽  
Imaging Biomarkers ◽  
In Vivo Evaluation ◽  
Non Invasive ◽  
Positron Emission ◽  
Magnetic Resonance Imaging Mri

Multiple sclerosis (MS) is a complex disease, where several processes can be selected as a target for positron emission topography (PET) imaging. Unlike magnetic resonance imaging (MRI), PET provides specific and quantitative information, and unlike neuropathology, it can be non-invasively applied to living patients, which enables longitudinal follow-up of the MS pathology. In the study of MS, PET can be useful for in vivo evaluation of specific pathological characteristics at various stages of the disease. Increased understanding of the progressive MS pathology will enhance the treatment options of this undertreated condition. The ultimate goal of developing and expanding PET in the study of MS is to have clinical non-invasive in vivo imaging biomarkers of neuroinflammation that will help to establish prognosis and accurately measure response to therapeutics. This topical review provides an overview of the promises and challenges of the use of PET in MS.

P2765Efficacy of venous recanalization by noninvasive pulsed cavitational ultrasound therapy on swine model of acute deep venous thrombosis

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
L Khider ◽  
G Goudot ◽  
C Del Giudice ◽  
T Mirault ◽  
P Bruneval ◽  
...  
Keyword(s):  
Venous Thrombosis ◽  
Deep Venous Thrombosis ◽  
Surrounding Tissue ◽  
Ultrasound Therapy ◽  
Swine Model ◽  
High Morbidity ◽  
Linear Probe ◽  
Venous Recanalization

Abstract Background Post thrombotic syndrome is a frequent complication of deep venous thrombosis and is associated with high morbidity and hospitalization. Treatments currently available are invasive, involve use of endovenous procedures with stents and balloons, and frequently require general anesthesia. Pulsed cavitational ultrasound therapy (PCUT) emerged recently as a new technique to destroy remotely soft tissue. We recently demonstrated that PCUT was able to recanalize non-invasively in in vitro model of acute venous thrombosis (human blood clot). Purpose We aim to test the safety and efficacy of venous recanalization by noninvasive PCUT in vivo swine model of acute venous thrombosis. Methods All the experiments were performed on White large X Landrace swine. We induced an acute femoral deep venous thrombosis by using occlusive balloons introduced from jugular and popliteal vein combined with local injection of 50 IU of human thrombin. A 3 cm length occlusive thrombosis was obtained after 2 hours. Swines 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 the follow up all swines received curative anticoagulation. To achieve PCUT, a 2.25 MHz transducer centered by a linear probe was used and cavitation was obtained in the center of the vein (Figure). After manual determination of thrombus location, a robotic arm was used to automatically move the transducer along the thrombus. Effectiveness of recanalization was evaluated by echo-Doppler and phlebography. Safety was assessed by Doppler ultrasound of the insonified area (artery, veins and surrounding tissue) and by histological analysis (local femoral vein and artery and lungs for pulmonary embolism). Results Among the 24 swines, we obtained 22 occlusive venous thromboses and 2 partial. The median length of the thrombus was 26±4.4 mm with vein diameter of 8.5±1.6 mm. Acutely, thrombosis recanalization was systematically obtained among the 19 swine with PCUT with median treatment duration of 33 minutes with residual diameter of 2.9±0.9 mm. No extravasation of contrast material or hematoma was observed after the therapy. After a 14-day follow-up, 75% of recanalisation remain permeable vs. 0% of vein permeable in the no therapy group (p=0.008). Residual diameter was 2.6±1.2 mm, which correspond to 50% of the venous diameter. No vein or artery damage and no embolism or pulmonary infarction was observed in all pigs. Figure 1 Conclusion We have demonstrated in vivo the safety and the efficacy of PCUT for non-invasive venous recanalization, persistent after 2 weeks. Acknowledgement/Funding French society of cardiology

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