Olivier Villemain

Selective propensity of bovine jugular vein material to bacterial adhesions: An in-vitro study

BACKGROUND Percutaneous pulmonary valve implantation (PPVI) using Melody valve made of bovine jugular vein is safe and effective. However, infective endocarditis has been reported for unclear reasons. We sought to assess the impact of valvular substrates on selective bacterial adhesion. METHODS Three valved stents (Melody valve, homemade stents with bovine and porcine pericardium) were tested in-vitro for bacterial adhesion using Staphylococcus aureus and Streptococcus sanguinis strains. RESULTS Bacterial adhesion was higher on bovine jugular venous wall for S. aureus and on Melody valvular leaflets for S. sanguinis in control groups and significantly increased in traumatized Melody valvular leaflets with both bacteria (traumatized vs non traumatized: p=0.05). Bacterial adhesion was lower on bovine pericardial leaflets. CONCLUSION Selective adhesion of S. aureus and S. sanguinis pathogenic strains to Melody valve tissue was noted on healthy tissue and increased after implantation procedural steps.

Ultrafast Harmonic Coherent Compound (UHCC) Imaging for High Frame Rate Echocardiography and Shear-Wave Elastography

Transthoracic shear-wave elastography (SWE) of the myocardium remains very challenging due to the poor quality of transthoracic ultrafast imaging and the presence of clutter noise, jitter, phase aberration, and ultrasound reverberation. Several approaches, such as diverging-wave coherent compounding or focused harmonic imaging, have been proposed to improve the imaging quality. In this study, we introduce ultrafast harmonic coherent compounding (UHCC), in which pulse-inverted diverging waves are emitted and coherently compounded, and show that such an approach can be used to enhance both SWE and high frame rate (FR) B-mode Imaging. UHCC SWE was first tested in phantoms containing an aberrating layer and was compared against pulse-inversion harmonic imaging and against ultrafast coherent compounding (UCC) imaging at the fundamental frequency. In vivo feasibility of the technique was then evaluated in six healthy volunteers by measuring myocardial stiffness during diastole in transthoracic imaging. We also demonstrated that improvements in imaging quality could be achieved using UHCC B-mode imaging in healthy volunteers. The quality of transthoracic images of the heart was found to be improved with the number of pulse-inverted diverging waves with a reduction of the imaging mean clutter level up to 13.8 dB when compared against UCC at the fundamental frequency. These results demonstrated that UHCC B-mode imaging is promising for imaging deep tissues exposed to aberration sources with a high FR.

Pulsed cavitational ultrasound for non-invasive chordal cutting guided by real-time 3D echocardiography

AIMS Basal chordae surgical section has been shown to be effective in reducing ischaemic mitral regurgitation (IMR). Achieving this section by non-invasive mean can considerably decrease the morbidity of this intervention on already infarcted myocardium. We investigated in vitro and in vivo the feasibility and safety of pulsed cavitational focused ultrasound (histotripsy) for non-invasive chordal cutting guided by real-time 3D echocardiography. METHODS AND RESULTS Experiments were performed on 12 sheep hearts, 5 in vitro on explanted sheep hearts and 7 in vivo on beating sheep hearts. In vitro, the mitral valve (MV) apparatus including basal and marginal chordae was removed and fixed on a holder in a water tank. High-intensity ultrasound pulses were emitted from the therapeutic device (1-MHz focused transducer, pulses of 8 µs duration, peak negative pressure of 17 MPa, repetition frequency of 100 Hz), placed at a distance of 64 mm under 3D echocardiography guidance. In vivo, after sternotomy, the same therapeutic device was applied on the beating heart. We analysed MV coaptation and chordae by real-time 3D echocardiography before and after basal chordal cutting. After sacrifice, the MV apparatus were harvested for anatomical and histological post-mortem explorations to confirm the section of the chordae. In vitro, all chordae were completely cut after a mean procedure duration of 5.5 ± 2.5 min. The procedure duration was found to increase linearly with the chordae diameter. In vivo, the central basal chordae of the anterior leaflet were completely cut. The mean procedure duration was 20 ± 9 min (min = 14, max = 26). The sectioned chordae was visible on echocardiography, and MV coaptation remained normal with no significant mitral regurgitation. Anatomical and histological post-mortem explorations of the hearts confirmed the section of the chordae. CONCLUSIONS Histotripsy guided by 3D echo achieved successfully to cut MV chordae in vitro and in vivo in beating heart. We hope that this technique will open the door in the near future to the non-invasive treatment of functional IMR.

Imaging the dynamics of cardiac fiber orientation in vivo using 3D Ultrasound Backscatter Tensor Imaging

The assessment of myocardial fiber disarray is of major interest for the study of the progression of myocardial disease. However, time-resolved imaging of the myocardial structure remains unavailable in clinical practice. In this study, we introduce 3D Backscatter Tensor Imaging (3D-BTI), an entirely novel ultrasound-based imaging technique that can map the myocardial fibers orientation and its dynamics with a temporal resolution of 10 ms during a single cardiac cycle, non-invasively and in vivo in entire volumes. 3D-BTI is based on ultrafast volumetric ultrasound acquisitions, which are used to quantify the spatial coherence of backscattered echoes at each point of the volume. The capability of 3D-BTI to map the fibers orientation was evaluated in vitro in 5 myocardial samples. The helicoidal transmural variation of fiber angles was in good agreement with the one obtained by histological analysis. 3D-BTI was then performed to map the fiber orientation dynamics in vivo in the beating heart of an open-chest sheep at a volume rate of 90 volumes/s. Finally, the clinical feasibility of 3D-BTI was shown on a healthy volunteer. These initial results indicate that 3D-BTI could become a fully non-invasive technique to assess myocardial disarray at the bedside of patients.

Noninvasive Imaging of the Coronary Vasculature Using Ultrafast Ultrasound

Objectives The aim of this study was to investigate the potential of coronary ultrafast Doppler angiography (CUDA), a novel vascular imaging technique based on ultrafast ultrasound, to image noninvasively with high sensitivity the intramyocardial coronary vasculature and quantify the coronary blood flow dynamics. Background Noninvasive coronary imaging techniques are currently limited to the observation of the epicardial coronary arteries. However, many studies have highlighted the importance of the coronary microcirculation and microvascular disease. Methods CUDA was performed in vivo in open-chest procedures in 9 swine. Ultrafast plane-wave imaging at 2,000 frames/s was combined to an adaptive spatiotemporal filtering to achieve ultrahigh-sensitive imaging of the coronary blood flows. Quantification of the flow change was performed during hyperemia after a 30-s left anterior descending (LAD) artery occlusion followed by reperfusion and was compared to gold standard measurements provided by a flowmeter probe placed at a proximal location on the LAD (n = 5). Coronary flow reserve was assessed during intravenous perfusion of adenosine. Vascular damages were evaluated during a second set of experiments in which the LAD was occluded for 90 min, followed by 150 min of reperfusion to induce myocardial infarction (n = 3). Finally, the transthoracic feasibility of CUDA was assessed on 2 adult and 2 pediatric volunteers. Results Ultrahigh-sensitive cine loops of venous and arterial intramyocardial blood flows were obtained within 1 cardiac cycle. Quantification of the coronary flow changes during hyperemia was in good agreement with gold standard measurements (r2 = 0.89), as well as the assessment of coronary flow reserve (2.35 ± 0.65 vs. 2.28 ± 0.84; p = NS). On the infarcted animals, CUDA images revealed the presence of strong hyperemia and the appearance of abnormal coronary vessel structures in the reperfused LAD territory. Finally, the feasibility of transthoracic coronary vasculature imaging was shown on 4 human volunteers. Conclusions Ultrafast Doppler imaging can map the coronary vasculature with high sensitivity and quantify intramural coronary blood flow changes.

Myocardial Stiffness Assessment Using Shear Wave Imaging in Pediatric Hypertrophic Cardiomyopathy

The pathophysiology of hypertrophic cardiomyopathy (HCM) is characterized by an increase of ventricular stiffness in most patients. Diastolic dysfunction in HCM is related to the alteration of the myocardial passive stiffness (MS) that modifies left ventricular relaxation. However, evaluation of

Pulsed Cavitational Ultrasound Softening: A New Noninvasive Therapeutic Approach for Calcified Bioprosthetic Valve Stenosis

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French national survey on infective endocarditis and the Melody™ valve in percutaneous pulmonary valve implantation

BACKGROUND Percutaneous pulmonary valve implantation (PPVI) is a routine treatment for dysfunctional right ventricular outflow tract. Infective endocarditis (IE) is a major concern. AIM To report French experience with the Melody™ valve (Medtronic Inc., Minneapolis, MN, USA). METHODS All patients who underwent PPVI were recorded in a multicentre French national survey. Demographic and procedural data were collected from patients with IE. Bacterial identification, diagnostic tools and outcome were recorded. RESULTS Forty-five cases of IE were diagnosed in 43 patients. The cumulative IE incidence was 11.8% (95% confidence interval [CI] 8.5-15.9). The annualized IE incidence was 3.6% (95% CI 0-4.8). Freedom from IE was 96.3% and 85.8% at 12 months and 60 months, respectively. IE incidence did not change during the study period. The mean interval between PPVI and IE was 2.6±2.1 years (range, 5 days to 7.3 years). Fifteen patients with IE required intravenous antibiotics only. Seven patients had early interventional cardiac catheterization to relieve severe right ventricular outflow tract obstruction. Twenty-four patients had surgical valve replacement (six urgently; nine semi-urgently; nine electively). Staphylococcus aureus IE required surgery in all but one patient. Three patients died before any treatment. Three additional patients died, giving a mortality rate of 14%. Global survival in the total cohort of patients who received a Melody valve was excellent (96.5% at 5 years). When comparing survival curves between the IE and non-IE groups, death and cardiovascular events were statistically significantly higher in the IE group (log-rank P<0.0001). CONCLUSION Melody valve IE is a severe complication following PPVI. The annualized IE incidence in this cohort was similar to rates reported in other studies. With rapid diagnosis and adequate treatment, outcome has improved, and unfavourable outcome is mainly associated with S. aureus.

Role of animal models for percutaneous atrial septal defect closure

As for any preclinical development of new implantable device, bench testing has been followed by experimental studies on large animal models for the development of atrial septal defect closure devices. Various models have been used according to studied species (porcine, ovine or canine model) and whether the septal defect was percutaneously or surgically created. Animal models of percutaneous atrial septal defect closure aim to assess the healing process and device endothelialisation, as well as the development of magnetic resonance imaging guided procedures, the short-term effects of volume overload on right ventricular contractility through haemodynamic studies and the understanding of other complications such as nickel hypersensitivity. Each technique has its own advantages and drawbacks, and leads to different punch-related, acute septal injuries that could have an effect on the healing process after device implantation. It has been suggested that some long-term, major device-related complications such as thrombosis or infective endocarditis may be associated with an inappropriate healing process or insufficient endothelialisation of the device, leading industrial companies to pay a great deal of attention to the healing process. Tissue reactions in animal models were shown to adequately reproduce the healing response after device implantation in humans, with an endothelial device coverage observed as early as 30 days after implantation and complete after 3 to 6 months. Research perspectives may evaluate both animal models and in-vitro studies in parallel with a view to clarify the endothelialisation process using human endothelial cells through in-vitro experiments. Self-sensing device for detecting the presence of endothelial cells on the surface of intracardiac occluders and high-resolution imaging techniques that could non-invasively assess the complete endothelialisation of a device would also be promising tools which would need large animal models studies before their clinical application.

Myocardial Stiffness Evaluation Using Noninvasive Shear Wave Imaging in Healthy and Hypertrophic Cardiomyopathic Adults

Objectives The goal of our study was to investigate the potential of myocardial shear wave imaging (SWI) to quantify the diastolic myocardial stiffness (MS) (kPa) noninvasively in adult healthy volunteers (HVs) and its physiological variation with age, and in hypertrophic cardiomyopathy (HCM) populations with heart failure and preserved ejection function (HFpEF). Background MS is an important prognostic and diagnostic parameter of the diastolic function. MS is affected by physiological changes but also by pathological alterations of extracellular and cellular tissues. However, the clinical assessment of MS and the diastolic function remains challenging. SWI is a novel ultrasound-based technique that has the potential to provide intrinsic MS noninvasively. Methods We prospectively included 80 adults: 60 HV (divided into 3 groups: 20- to 39-year old patients [n = 20]; 40- to 59-year-old patients [n = 20]; and 60- to 79-year-old patients [n = 20]) and 20 HCM-HFpEF patients. Echocardiography, cardiac magnetic resonance imaging and biological explorations were achieved. MS evaluation was performed using an ultrafast ultrasound scanner with cardiac phased array. The fractional anisotropy of MS was also estimated. Results MS increased significantly with age in the HV group (the mean MS was 2.59 ± 0.58 kPa, 4.70 ± 0.88 kPa, and 6.08 ± 1.06 kPa for the 20- to 40-year-old, 40- to 60-year-old, and 60- to 80-year-old patient groups, respectively; p < 0.01 between each group). MS was significantly higher in HCM-HFpEF patients than in HV patients (mean MS = 12.68 ± 2.91 kPa vs. 4.47 ± 1.68 kPa, respectively; p < 0.01), with a cut-off at 8 kPa (area under the curve = 0.993; sensitivity = 95%, specificity = 100%). The fractional anisotropy was lower in HCM-HFpEF (mean = 0.133 ± 0.073) than in HV (0.238 ± 0.068) (p < 0.01). Positive correlations were found between MS and diastolic parameters in echocardiography (early diastolic peak/early diastolic mitral annular velocity, r = 0.783; early diastolic peak/transmitral flow propagation velocity, r = 0.616; left atrial volume index, r = 0.623) and with fibrosis markers in cardiac magnetic resonance (late gadolinium enhancement, r = 0.804; myocardial T1 pre-contrast, r = 0.711). Conclusions MS was found to increase with age in healthy adults and was significantly higher in HCM-HFpEF patients. Myocardial SWI has the potential to become a clinical tool for the diagnostic of diastolic dysfunction. (Non-invasive Evaluation of Myocardial Stiffness by Elastography [Elasto-Cardio]; NCT02537041)