Pierre Dos Santos

University of Bordeaux · Department of Life and Health Sciences

Background Atrial fibrillation (AF) often transitions from paroxysmal to more sustained forms in a 4-15/100 person-year range(1). It is well-recognized from both clinical and animal studies that some individuals undergo this transition much more readily than others, but the underlying mechanisms remain unclear. Purpose To identify potential differ...

Aims From a patient and health system perspective, managing worsening heart failure (WHF) as an outpatient has become a priority. Remote management allows early detection of WHF, enabling timely intervention with the aim of preventing hospitalization. The objective of the study was to evaluate the feasibility and safety of remotely managing WHF eve...

Description of the cardiac myofiber architecture in pathological or even physiological conditions is essential for image-based modeling in electrophysiology or mechanical studies. While diffusion tensor imaging (DTI) is one of the best modalities to capture myofiber orientation of large mammalian hearts, validations of putative myofiber’s main orie...

Background Immune checkpoint inhibitors (ICIs) are widely used in lung cancer management. However, myocarditis, which is a rare, yet potentially severe adverse-related event associated with ICIs, could be under-reported. Objectives This study is aimed to prospectively evaluate the cumulative incidence rate of myocarditis, through systematic screen...

Structural remodeling is a common consequence of chronic pathological stresses imposed on the heart. Understanding the architectural and compositional properties of diseased tissue is critical to determine their interactions with arrhythmic behavior. Microscale tissue remodeling, below the clinical resolution, is emerging as an important source of...

The more recent studies of human pathologies have essentially revealed the complexity of the interactions involved at the different levels of integration in organ physiology. Integrated organ thus reveals functional properties not predictable by underlying molecular events. It is therefore obvious that current fine molecular analyses of pathologies...

Modifications of the myocardial architecture can cause abnormal electrical activity of the heart. Fibro-fatty infiltrations have been implicated in various cardiac pathologies associated with arrhythmias and sudden cardiac death, such as arrhythmogenic right ventricular cardiomyopathy (ARVC). Here, we report the development of an MRI protocol to ob...

Aims We documented the midterm prognosis of left ventricular thrombus (LVT) in heart failure (HF) patients with dilated cardiomyopathy (DCM) and ischaemic cardiomyopathy (ICM). We aimed to characterize patients with LVT in the context of HF with reduced (≤40%) left ventricular ejection fraction and evaluate their risk for death and/or embolic event...

Introduction Atrial Fibrillation (AF) stabilization depends on remodelling processes affecting the electrophysiological, metabolic, and structural properties of the atrial muscle. Objective Develop an AF Sheep model to study the electrophysiogical, structural and bioenergetic remodelling of the cardiac tissue. Methods An algorithm controlled pace...

Background Growing evidence implicates cardiac energetic metabolism in cardiac arrhythmogenesis. Here, we focused on the role of an alternative pathway of glycolysis, the hexosamines biosynthetic pathway (HBP). This pathway usually represents less than 5% of metabolic pathways, however it has been shown to be increased in some cardiomyopathies. HBP...

Findings Here, we demonstrate that OP2113 (5-(4-Methoxyphenyl)-3H-1,2-dithiole-3-thione, CAS 532-11-6), synthesized and used as a drug since 1696, does not act as an unspecific antioxidant molecule (i.e., as a radical scavenger) but unexpectedly decreases mitochondrial reactive oxygen species (ROS/H2O2) production by acting as a specific inhibitor...

Effect of OP2113 on mitochondrial NADH oxidase activity. After freeze-thaw treatment, rat heart mitochondria were used to assess mitochondrial rotenone-sensitive NADH oxidase activity by polarography as described in the supplementary Materials and Methods. Panel A: Typical polarographic trace showing the rotenone-sensitive NADH oxidase activity and...

Detailed information and pictures about ischemia/reperfusion in rat heart. Supporting data contain supplementary informations concerning the experiments on isolated rat heart ischemia and reperfusion. Raw data presents contractile activity (RPP), whole heart oxygen consumption (MVO2) during the pre-schemic and post-ischemic (reperfusion) phases for...

Effect of OP2113 on the artificial H2O2-producing NAD(P)H oxidase system. The rates of H2O2 production were measured in the presence of NAD(P)H oxidase (1 mU/ml) and NADH (150 μM), and in the absence of heart mitochondria. Data are based on 3 independent experiments, each performed in duplicate. No significant effect of OP2113 on this experimental...

Background: The FRANCE-2 registry (French Aortic National Corevalve and Edwards) previously reported good early- and medium-term clinical and echocardiographic efficacy for transcatheter aortic valve replacement. We here report 5-year follow-up results from the registry. Methods: The registry includes all consecutive patients undergoing transcat...

Purpose Heart failure (HF) is a common, serious, and still poorly known illness, which might benefit from studies in claims databases. However, to provide reliable estimates, HF patients must be adequately identified. This validation study aimed to estimate the diagnostic accuracy of the International Classification of Diseases, Tenth Revision (ICD...

Introduction Large animal ex vivo biventricular working hearts are a recent breakthrough in the scientific experimental community. This model allows a greater insight into intrinsic cardiac electrophysiology and hemodynamic function without interference from autonomous nervous system. Objective Perform a comparative study between different perfusi...

Background: Ventricular arrhythmia is common after left ventricular assist device (LVAD) implantation, especially in the early postoperative phase (<30 days). Aim: To identify the incidence of and risk factors for electrical storm (ES) occurring within 30 days of HeartMate® II implantation. Methods: We reviewed data from all consecutive patien...

Background: Pulmonary arterial hypertension (PAH) is a rare complication of systemic lupus erythematosus (SLE). Methods: We identified all SLE-PAH patients enrolled in the French Pulmonary Hypertension (PH) Registry with a diagnosis confirmed by right heart catheterization (RHC). A control group of 101 SLE patients without known PAH (SLE-non PAH...

Background: Transcatheter aortic valve replacement (TAVR) has revolutionized management of high-risk patients with severe aortic stenosis. However, survival and the incidence of severe complications have been assessed in relatively small populations and/or with limited follow-up. Objectives: This report details late clinical outcome and its dete...

Transcatheter aortic valve replacement (TAVR) has revolutionized management of high-risk patients with severe aortic stenosis. However, survival and the incidence of severe complications have been assessed in relatively small populations and/or with limited follow-up.

Background: Left ventricular (LV) afterload could be associated with reduced myocardial contractility. The aim of this study was to evaluate the relative impact of increased afterload on LV myocardial deformation indices in chronic aortic constriction, with regard to hypertrophy, myocardial fibrosis, and mitochondrial function, and to differentiat...

Introduction: Gradual alterations in cardiac energy balance, as assessed by the myocardial PCr/ATP-ratio, are frequently associated with the development of cardiac disease. Despite great interest for the follow-up of myocardial PCr and ATP content, cardiac MR-spectroscopy in rat models in vivo is challenged by sensitivity issues and cross-contamin...

The onset of right ventricular dysfunction in patients presenting with congenital heart disease is associated with a dismal long-term outcome and often represents a therapeutic dead end. Our study had several objectives: (1) to analyse the anatomical, functional, histological and cellular characteristics of an animal model of repaired tetralogy of...

Background The hexosamine biosynthetic pathway (HBP) is heightened in cardiomyopathies. We aimed at understanding how over-activation of HBP impacts on cardiac electrophysiology, and acts as a trigger or a substrate of cardiac arrhythmias. Methods Overactivation of the HBP by injection of glucosamine (GlcN 270mg/kg) was assessed under basal condit...

Background Calcium leak from the sarcoplasmic reticulum (SR) favors cardiac sudden death through a calcium overload mechanism. Here we investigate the crosstalk between the calcium overload SR-mediated and the mitochondrial permeability transition pore (mPTP) opening during a ventricular arrhythmic episode. Methods and results a burst pacing proto...

To provide a model close to the human heart, and to study intrinsic cardiac function at the same time as electromechanical coupling, we developed a magnetic resonance (MR)-compatible set-up of isolated working perfused pig hearts. Hearts from pigs (40kg, N=20) and sheep (N=1) were blood-perfused ex vivo in the working mode with and without loaded r...

Rhythmic complications seem common after left ventricular (LV) assist device (LVAD), especially in the early phase of implantation (<30 days). We sought to identify the incidence and risk factors of arrhythmic storm (AS) occuring after Heart Mate® 2 device (HM2, Thoratec Corporation, Plesanton, CA, USA) implantation. All patients with HM2 implanted...

Background Heart failure is the leading cause of hospital admissions and economic burden. In accordance with guidelines, a dedicated heart failure unit has been created in Bordeaux (France) in May 2011. Aim Evaluate the impact of a heart failure management unit with ambulatory sector on readmission rate and mortality; and identify prognosis paramet...

To investigate transcatheter aortic valve implantation (TAVI) feasibility, effectiveness and safety in radiation-induced aortic valve stenosis cases. 198 consecutive patients referred for TAVI were prospectively enrolled. They were divided into two groups: patients with a history of chest radiation therapy with suspected radiation-induced valvular...

Introduction: Phosphorus magnetic resonance spectroscopy (31P-MRS) makes a unique and valuable contribution to understand how mitochondrial energy supply responds to ATP demand in beating hearts. Changes in PCr/ATP allow detecting energy dysbalance that often predict disease and mortality. However, MR techniques in vivo are challenged by tissue con...

A 47-year-old man with severe radiation-induced aortic stenosis was rejected for cardiac surgery because of porcelain aorta. We successfully implanted an Edwards SAPIEN valve (Edwards Lifesciences, Irvine, CA), but the patient was readmitted 3 weeks later for heart failure with a continuous murmur on auscultation. Echocardiography showed a small de...

Phosphorus magnetic resonance spectroscopy (31P-MRS) makes a unique and valuable contribution to our understanding of heart energetics, by giving the car- diac energy status from the concentrations of ATP and phosphocreatine (PCr). Changes in PCr/ATP ratio allow detecting energy imbalance that predicts disease and mortality. However, localized MR t...

Rationale: Severe asthma is a major public health issue throughout the world. Increased bronchial smooth muscle (BSM) mass, a characteristic feature of airway remodeling in severe asthma, is associated with resistance to high-intensity treatment and poor prognosis. In vitro, the Ca(2+)-channel blocker gallopamil decreased the proliferation of BSM...

The more recent studies of human pathologies have essentially revealed the complexity of the interactions involved at the different levels of integration in organ physiology. Integrated organ thus reveals functional properties not predictable by underlying molecular events. It is therefore obvious that current fine molecular analyses of pathologies...

Guzun, R., Kaambre, T., Bagur, R., Grichine, A., Usson, Y., Varikmaa, M. Anmann, T., Tepp, K., Timohhina, N., Shevchuk, I., Chekulayev, V., Boucher, F., Dos Santos, P., Schlattner, U., Wallimann, T., Kuznetsov, A. V., Dzeja, P., Aliev, M., Saks, V. "Modular organization of cardiac energy metabolism: energy conversion, transfer and feedback regulati...

Cardiac diseases are essentially multifactorial problems affecting numerous interactions and kinetic properties in highly organized cell, tissue and organ structures. Therefore, an exhaustive investigation of the effects of cardiac drugs and adaptations needs integrative approaches. Based on rigorously founded theory, metabolic control analysis (MC...

Background Rhythmic complications seem common after left ventricular (LV) assist device (LVAD), especially in the early phase of implantation (<30 days). We sought to identify the incidence and risk factors of arrhythmic storm occuring after Heart Mate® 2 (HM2) implantation. Methods All patients with HM2 implanted in our institution have been studi...

To meet high cellular demands, the energy metabolism of cardiac muscles is organized by precise and coordinated functioning of Intra-Cellular Energetic Units (ICEUs). ICEUs represent structural and functional modules integrating multiple fluxes at sites of ATP generation in mitochondria and ATP utilization by myofibrillar, sarcoplasmic reticulum an...

Background: A 62-year-old man was admitted for severe heart failure. Echocardiography revealed an aortic stenosis and a poor left ventricular ejection fraction (LVEF) with an intraventricular blood clot. The situation was transiently stabilised with dobutamine and furosemide but, after a few days, he developed heparin-induced thrombocytopaenia. Oth...

Severe anaphylactoid reaction after the use of iodinated contrast media are rare but can contraindicate the use of contrast agent. It was the case of a 53-year-old woman suffering from symptomatic severe aortic stenosis, recused for cardiac surgery because of deleterious effects of chest-wall irradiation, with porcelain aorta. We decided to implant...

Hypoxic states of the cardiovascular system are often associated with severe cardiac diseases. In spite of impairments in contractile activity, mitochondrial content, cell energy status and calcium transients, we recently demonstrated an improved energy homeostasis in chronic hypoxic hearts explained by a higher mitochondrial sensitivity to ATP/PCr...

Our aim is to propose an inovative non-invasive analysis of heart contraction energetics, to be used for diagnosis and therapeutics follow-up in human heart pathologies. The analysis is based on the combination of non-invasive 31P-NMR and IRM techniques and the analytical background of metabolic modular control analysis (MoCA). Metabolic control an...

Although epidemiologic analyses suggest a correlation between higher rates of cardiovascular disease and chronic hyperglycemia, to date, no randomized clinical trial has convincingly demonstrated a beneficial effect of intensive therapy on macrovascular outcomes in individuals with long-standing type 2 diabetes. In contrast, intensive initial contr...

Because of the balance between ATP supply and ATP demand, alterations in cardiac energetics potentially affect cardiac work and may explain pathologies. Neverthelesss energetics alterations in each compartment remain unknown. Since mitochondrial oxidative phosphorylation is the main process of energy supply, mitochondrial sensitivity to energetic i...

Background: To date, Doppler echocardiography is the most widespread and well-recognized technique for the noninvasive evaluation of systolic pulmonary artery pressure (sPAP). However, recent studies have reported reservations about the relevance of Doppler echocardiography or the tool's reliability in the diagnosis and follow-up of patients with...

Background: Contact force (CF) is an important determinant of lesion formation for atrial endocardial radiofrequency ablation. There are minimal published data on CF and ventricular lesion formation. We studied the impact of CF on lesion formation using an ovine model both endocardially and epicardially. Methods and results: Twenty sheep receive...

Atherosclerosis is a chronic, progressive inflammatory disease that may develop into vulnerable lesions leading to thrombosis. To interrogate the molecular components involved in this process, single-chain variable fragments (scFvs) from a semi-synthetic human antibody library were selected on the lesions induced in a rabbit model of atherosclerosi...

The comprehensive study of human pathologies has revealed the complexity of the interactions involved in cardiovascular physiology. The recent validation of system's biology approaches - like our Modular Control and Regulation Analysis (MoCA) - motivates the current interest for new integrative and non-invasive analyses that could be used for medic...

Transcatheter aortic-valve implantation (TAVI) is an emerging intervention for the treatment of high-risk patients with severe aortic stenosis and coexisting illnesses. We report the results of a prospective multicenter study of the French national transcatheter aortic-valve implantation registry, FRANCE 2. All TAVIs performed in France, as listed...

Comparison of Ventricular Radiofrequency Lesions in Sheep. Introduction: In vivo assessment of RF ablation lesions is limited. Improved feedback could affect procedural outcome. A novel catheter, IRIS™ Cardiac Ablation Catheter (IRIS), enabling direct tissue visualization during ablation, was compared to a 3.5 mm open-irrigated tip ThermoCool™ Cath...

Dehydroepiandrosterone (DHEA) prevents chronic hypoxia-induced pulmonary hypertension and associated right ventricle dysfunction in rats. In this animal model, reoxygenation following hypoxia reverses pulmonary hypertension but not right ventricle dysfunction. We thus studied the effect of DHEA on the right ventricle after reoxygenation, i.e. after...

In vivo phage display selection is a powerful strategy for directly identifying agents that target the vasculature of normal or diseased tissues in living animals. We describe here a new in vivo biopanning strategy in which a human phage single-chain antibody (scFv) library was injected into high-fat diet-fed ApoE(-/-) mice. Extracellular and inter...

Background. Metaboreflex overactivation has been proprosed to explain exaggerated hyperventilation in heart failure population. We investigated the metaboreflex activation after cardiac resynchronization therapy (CRT). Methods. 10 heart failure patients (mean left ventricular ejection fraction (LVEF) 27 ± 4%) schedulded for CRT implantation were pr...

The relationship between depression and heart failure is neither coincidental nor trivial, since depression is a powerful predictor of re-hospitalization and mortality. We prospectively studied the prevalence and impact of depression on the clinical outcomes of patients attending for cardiac resynchronization therapy (CRT). We specifically examined...

In the past 5 years a few number of studies and case reports have come out focusing on biventricular (BiV) stimulation for treatment of congenital heart disease related ventricular dysfunction. The few available studies include a diverse group of pathophysiological entities ranging from a previously repaired tetralogy of Fallot (TOF) to a functiona...

Introduction: Patients who have undergone repair of Tetralogy of Fallot (TOF) often present with right bundle branch block. Cardiac resynchronization therapy (CRT) with right ventricular (RV) or biventricular (BiV) stimulation has been proposed as a modality to correct electrical abnormalities and improve cardiac contractility in patients with rep...