Francis Bessière

Periatrial epicardial fat is associated with markers of endothelial dysfunction in patients with atrial fibrillation.

Background Epicardial adipose tissue (EAT) is associated to atrial fibrillation (AF) burden and outcome after AF ablation. We intended to determine whether global or local EAT is associated with systemic and/or left atrial (LA) inflammation and markers of endothelial dysfunction in AF patients. Methods and Results Total, atrial, and ventricular EAT volume (EATtotal, EATatrial, EATventricular) were measured by multislice cardiac CT in 49 patients with paroxysmal (PAF, n=25) or persistent AF (PeF, n=24). Periatrial epicardial fat thickness at the esophagus (LA-ESO) and thoracic aorta (LA-ThA) were also measured. Vascular endothelial growth factor (VEGF), interleukin-8 (IL-8), soluble intercellular adhesion molecule 1 (sICAM-1), transforming growth factor-β1 (TGF-β1), and von Willebrand Factor (vWF) levels were measured in peripheral and LA blood samples obtained during catheterization during AF ablation. Patients with PeF had higher EATatrial (P<0.05) and LA-ESO (P=0.04) than patients with PAF. VEGF, IL-8, and TGF-β1 were not associated with EAT. In contrast, after adjusting for LA volume and body mass index, higher LA-ThA was significantly associated with higher sICAM-1 and vWF levels, both in peripheral blood (P<0.05) and in LA (P<0.05). Similar results were found with LA-ESO. Body mass index, EATtotal and EATventricular were not associated with sICAM-1 and vWF. Conclusions Periatrial epicardial fat showed a significant positive association with increased levels of sICAM-1 and vWF, which are biomarkers of endothelial dysfunction. No such associations were found when considering body mass index or EATtotal. These results suggest that local EAT rather than regional or total adiposity may modulate endothelial dysfunction in patients with AF.

Design and evaluation of a transesophageal HIFU probe for ultrasound-guided cardiac ablation: simulation of a HIFU mini-maze procedure and preliminary ex vivo trials

Atrial fibrillation (AF) is the most frequent cardiac arrhythmia. Left atrial catheter ablation is currently performed to treat this disease. Several energy sources are used, such as radio-frequency or cryotherapy. The main target of this procedure is to isolate the pulmonary veins. However, significant complications caused by the invasive procedure are described, such as stroke, tamponade, and atrioesophageal fistula, and a second intervention is often needed to avoid atrial fibrillation recurrence. For these reasons, a minimally-invasive device allowing performance of more complex treatments is still needed. High-intensity focused ultrasound (HIFU) can cause deep tissue lesions without damaging intervening tissues. Left atrial ultrasound-guided transesophageal HIFU ablation could have the potential to become a new ablation technique. The goal of this study was to design and test a minimally-invasive ultrasound-guided transesophageal HIFU probe under realistic treatment conditions. First, numerical simulations were conducted to determine the probe geometry, and to validate the feasibility of performing an AF treatment using a HIFU mini-maze (HIFUMM) procedure. Then, a prototype was manufactured and characterized. The 18-mm-diameter probe head housing contained a 3-MHz spherical truncated HIFU transducer divided into 8 rings, with a 5-MHz commercial transesophageal echocardiography (TEE) transducer integrated in the center. Finally, ex vivo experiments were performed to test the impact of the esophagus layer between the probe and the tissue to treat, and also the influence of the lungs and the vascularization on lesion formation. First results show that this prototype successfully created ex vivo transmural myocardial lesions under ultrasound guidance, while preserving intervening tissues (such as the esophagus). Ultrasound-guided transesophageal HIFU can be a good candidate for treatment of AF in the future.

Cardiac shear-wave elastography using a transesophageal transducer: application to the mapping of thermal lesions in ultrasound transesophageal cardiac ablation.

Heart rhythm disorders, such as atrial fibrillation or ventricular tachycardia can be treated by catheter-based thermal ablation. However, clinically available systems based on radio-frequency or cryothermal ablation suffer from limited energy penetration and the lack of lesions extent monitoring. An ultrasound-guided transesophageal device has recently successfully been used to perform High-Intensity Focused Ultrasound (HIFU) ablation in targeted regions of the heart in vivo. In this study we investigate the feasibility of a dual therapy and imaging approach on the same transesophageal device. We demonstrate in vivo that quantitative cardiac shear-wave elastography (SWE) can be performed with the device and we show on ex vivo samples that transesophageal SWE can map the extent of the HIFU lesions. First, SWE was validated with the transesophageal endoscope in one sheep in vivo. The stiffness of normal atrial and ventricular tissues has been assessed during the cardiac cycle (n = 11) and mapped (n = 7). Second, HIFU ablation has been performed with the therapy-imaging transesophageal device in ex vivo chicken breast samples (n  =  3), then atrial (left, n = 2) and ventricular (left n = 1, right n = 1) porcine heart tissues. SWE provided stiffness maps of the tissues before and after ablation. Areas of the lesions were obtained by tissue color change with gross pathology and compared to SWE. During the cardiac cycle stiffness varied from 0.5   ±   0.1 kPa to 6.0   ±   0.3 kPa in the atrium and from 1.3   ±   0.3 kPa to 13.5   ±   9.1 kPa in the ventricles. The thermal lesions were visible on all SWE maps performed after ablation. Shear modulus of the ablated zones increased to 16.3   ±   5.5 kPa (versus 4.4   ±   1.6 kPa before ablation) in the chicken breast, to 30.3   ±   10.3 kPa (versus 12.2   ±   4.3 kPa) in the atria and to 73.8   ±   13.9 kPa (versus 21.2   ±   3.3 kPa) in the ventricles. On gross pathology, the size of the lesions ranged from 0.1 to 1.5 cm(2) in the imaging plane area. Elasticity-estimated depths and widths of the lesions differed respectively with a median of 0.2 mm (first quartile Q1:  -0.8 mm; third quartile Q3: 2.6 mm) for a mean squared error (MSE) of 5.1 mm(2) and a median of 0.2 mm (Q1:  -2.7 mm; Q3: 2.7 mm) for a MSE of 11.1 mm(2) from gross pathology. We have demonstrated the feasibility of the HIFU thermal ablation monitoring using a dual therapy and imaging transesophageal device. The combination of HIFU, ultrasound imaging and SWE on the same transesophageal system could lead to a new clinical device for a safer and controlled treatment of a wide variety of cardiac arrhythmias.

Focal Transcatheter Cryoablation: Is a Four-Minute Application Still Required?: Focal Transcatheter Cryoablation

The standard 4‐minute application time for transcatheter cryoablation was determined in the 1990s when the system employed less potent chlorofluorocarbon refrigerants. The current refrigerant, nitrous oxide, generates substantially colder temperatures, with a faster cooling rate.

Cardiac Phenotype and Long-Term Follow-Up of Patients With Mutations in NKX2-5 Gene.

One of the essential homeobox transcription factors orchestrating cardiac embryologic development is NKX2-5 [(1)][1]. Mutations in NKX2-5 were initially discovered in inherited atrial septal defect (ASD) associated with atrioventricular block (AVB) [(2)][2], but were further found linked to other

Pulmonary vein hematoma after atrial fibrillation cryoablation: A new complication

c Cryoenergy is increasingly used to isolate the pulmonary veins (PVs) in patients with paroxysmal atrial fibrillation. Among 200 alloon cryoablations performed between 2009 and 2011, we eport 2 cases of PV hematoma revealed by postprocedural heoptysis. A 77-year-old woman and a 56-year-old man with a history of rug-resistant paroxysmal atrial fibrillation were referred for cryoblation. PV isolation was achieved by using a 23-mm balloon Arcticfront; Medtronic, Lyon, France). Vein temperature reached̃

Transoesophageal HIFU for cardiac ablation: In-vivo experiments in non-human primates

Transesophageal HIFU was proposed as an alternative to the current atrial fibrillation treatments. The present work described a feasibility study of transesophageal thermal ablation in the heart of non-human primates. An endoscope integrating a 5MHz 64-element commercial transesophageal echocardiography probe and a 8-element HIFU transducer was built. The transducer was cooled at 5°C and ultrasonic beam could be steered over a 15 to 55 mm range. The probe was tested in-vivo on three 30kg-baboons. Left atrium and ventricles were exposed to repeated continuous sonications (4-15 times during 16s) at a focal intensity of 3000 W/cm². B-mode, shear-wave and passive elastographies were performed before and after treatments in an attempt to monitor thermal lesions. T1 mapping and contrast MR imaging were realized the day after treatment. Clinical states of the subjects during and after the treatment were positive. One lesion in the left ventricle could be evidenced by elastography and confirmed by MRI. Experiment...

Myocardial Thermal Ablation with a Transesophageal High-Intensity Focused Ultrasound Probe: Experiments on Beating Heart Models

Described here is a study of transesophageal thermal ablation of isolated and perfused beating hearts and non-human primates. An endoscope integrating a transesophageal echocardiography probe and a high-intensity focused ultrasound transducer was built and tested on five Langendorff-isolated hearts and three 30-kg baboons. B-Mode ultrasound, passive elastography and magnetic resonance imaging were performed to monitor thermal lesions. In isolated hearts, continuous and gated sonication parameters were evaluated with acoustic intensities of 9-12 W/cm2. Sonication parameters of gated exposures with 12 W/cm2 acoustic intensity for 5 min consistently produced visible lesions in the ventricles of isolated hearts. In animals, left atria and ventricles were exposed to repeated continuous sonications (4-15 times for 16 s) at an acoustic intensity at the surface of the transducer of 9 W/cm2. Clinical states of the baboons during and after the treatment were good. One suspected lesion in the left ventricle could be evidenced by elastography, but was not confirmed by magnetic resonance imaging. The transesophageal procedure therefore has the potential to create thermal lesions in beating hearts and its safety in clinical practice seems promising. However, further technical exploration of the energy deposition in the target would be necessary before the next pre-clinical experiments.

Transesophageal 2D ultrasound to 3D computed tomography registration for the guidance of a cardiac arrhythmia therapy

The work aims to develop a new image-processing method to improve the guidance of transesophageal high intensity focused ultrasound (HIFU) atrial fibrillation therapy. Our proposal is a novel registration approach that aligns intraoperative 2D ultrasound with preoperative 3D-CT information. This approach takes advantage of the anatomical constraints imposed at the transesophageal HIFU probe to simplify the registration process. Our proposed method has been evaluated on a physical phantom and on real clinical data.

First identification of homozygous truncating CSRP3 variants in two unrelated cases with hypertrophic cardiomyopathy

Hypertrophic cardiomyopathy (HCM) is the most common inherited cardiovascular disease with an estimated prevalence of 1/500. More than 40 genes have been reported to cause HCM. Among them, CSRP3 is usually included on HCM gene panels used for molecular diagnosis by next-generation sequencing (NGS). To provide new insights into the pathophysiology of hypertrophic cardiomyopathy, a NGS workflow based on a panel of 48 cardiomyopathies-causing genes was analyzed on a cohort of 542 HCM patients. As expected, this molecular approach led to identify most pathogenic or likely pathogenic variants into prevalent HCM-causing genes: MYBPC3 (123/542; 22.7%), MYH7 (48/542; 8.9%), TNNT2 (12/542; 2.2%), and TNNI3 (10/542; 1.8%). Among MYBPC3 variants, 96 led to a premature stop codon (78%). More surprisingly, our molecular study led also to detect, for the first time, homozygous CSRP3 truncating variants in two unrelated HCM probands. Meta-analysis of rare previously reported CSRP3 variants on HCM probands using ACMG guidelines indicate that only one variation (p.Cys58Gly) could be considered as likely pathogen. By combining meta-analysis results and identification of two unrelated HCM patients with homozygous CSRP3 truncating variants, we suggest that the association of CSRP3 as a validated HCM-causing gene require additional studies and those CSRP3 variants could result in HCM with an autosomal recessive inheritance rather than with an autosomal dominant transmission as usually reported on HCM (OMIM 612124).