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Objectives The objective of the study was to validate PCr/ATP ratios as an in vivo marker for cardiac mitochondrial function.Background Cardiac energy status, measured as PCr/ATP ratio with 31P-MRS in vivo, was shown to be a prognostic factor in heart failure and is lowered in cardiometabolic disease. As mitochondrial function is also hampered in these diseases and oxidative phosphorylation is the major contributor to ATP synthesis, the PCr/ATP ratio might be a reflection of cardiac mitochondrial function.Methods Thirty-eight patients scheduled for open heart surgery were enrolled in this study. Before surgery, cardiac 31P-MRS was performed. During surgery, tissue specimens from the right atrial appendage were obtained for the ex vivo assessment of mitochondrial function using high-resolution respirometry.Results The patient population included was heterogenous resulting in wide ranges of PCr/ATP ratios and ADP-stimulated respiration rates (PCr/ATP ranging from 0.533 to 1.717; ADP-stimulated respiration rates ranging from 28.5 to 94.6 pmol/mg/s). Correlation analysis however showed no relationship between PCr/ATP and ADP-stimulated respiration rates fueled by various substrates (octanoylcarnitine R2 2 2 = 0.005, p = 0.71; pyruvate R2 = 0.040, p = 0.26).Conclusions Our results do not support the use of cardiac energy status (PCr/ATP) as a surrogate marker of mitochondrial function in the heart. The dissociation of the two parameters in the present study suggests that mitochondrial function is not the only determinant of cardiac energy status.Condensed abstractThis study does not support the use of in vivo cardiac energy status (PCr/ATP ratio) as a surrogate marker of ex vivo mitochondrial function (maximal oxidative respiration). Although both PCr/ATP and mitochondrial function are reduced in cardiovascular disease, the dissociation of the two parameters in the present study shows that PCr/ATP is determined by more factors than only mitochondrial function. Hence, PCr/ATP is not a good marker for mitochondrial function, but it can be a valuable marker for cardiometabolic health in cardiometabolic studies.Trial registration: https://clinicaltrials.gov (NCT03049228).

To evaluate whether the simplified valve-sparing technique (SVST) implies clinical outcomes comparable or not with those of established David technique in the surgery of aortic root.We collected the records of patients who had undergone aortic root surgery with the SVST or standard David technique (SDT) at our institution between January 2009 and December 2018. The primary endpoints were the incidence of all-cause death, reoperation for any reason, and postoperative complications. The secondary endpoint was the midterm incidence of reoperation for aortic valve regurgitation.A total of 169 patients who underwent aortic root surgery were analyzed. SDT and SVST were performed in 48 (28.4%) and in 121 (71.6%) patients, respectively. Thirty-day mortality occurred in 0% and 0.8% of patients in the SDT and SVST groups, respectively. The rate of postoperative new permanent pacemaker implantation was 6.3% (three patients) and 0.8% (one patient) in SDT and SVST cohort, respectively (p = .07). The incidence of postoperative thromboembolic stroke was 6.3% and 2.5% in SDT and SVST groups, respectively (p = .23). The median follow-up time was 29 (23-47) months. During the FU period, no differences were found between two cohorts in terms of all-cause mortality (p = .99), the incidence of reoperation (p = .19), and incidence of aortic valve regurgitation requiring reoperation (p = .58).The SVST appears to be safe and feasible showing early clinical results comparable to the SDT. Nevertheless, further studies with larger series and long-term follow-ups are required to demonstrate its safety and efficacy.

International audience; Since the SARS-CoV-2 pandemic, the potential of exhaled breath (EB) to provide valuable information and insight into the health status of a person has been revisited. Mass spectrometry (MS) has gained increasing attention as a powerful analytical tool for clinical diagnostics of exhaled breath aerosols (EBA) and exhaled breath condensates (EBC) due to its high sensitivity and specificity. Although MS will continue to play an important role in biomarker discovery in EB, its use in clinical setting is rather limited. EB analysis is moving toward online sampling with portable, room temperature operable, and inexpensive point-of-care devices capable of real-time measurements. This transition is happening due to the availability of highly performing biosensors and the use of wearable EB collection tools, mostly in the form of face masks. This feature article will outline the last developments in the field, notably the novel ways of EBA and EBC collection and the analytical aspects of the collected samples. The inherit non-invasive character of the sample collection approach might open new doors for efficient ways for a fast, non-invasive, and better diagnosis.

International audience; Myocardial ischemia–reperfusion injury (MIRI) induces life-threatening damages to the cardiac tissue, and pharmacological means to achieve cardioprotection are sorely needed. MIRI severity varies along the day–night cycle and is molecularly linked to components of the cellular clock, including the nuclear receptor REV-ERBα, a transcriptional repressor. Here we show that digoxin administration in mice is cardioprotective when timed to trigger REV-ERBα protein degradation. In cardiomyocytes, digoxin increases REV-ERBα ubiquitinylation and proteasomal degradation, which depend on REV-ERBα’s ability to bind its natural ligand, heme. Inhibition of the membrane-bound Src tyrosine-kinase partially alleviated digoxin-induced REV-ERBα degradation. In untreated cardiomyocytes, REV-ERBα proteolysis is controlled by several E3 ubiquitin ligases and the proteasome subunit PSMB5. Among these, only SIAH2 and PSMB5 contributed to digoxin-induced degradation of REV-ERBα. Thus, controlling REV-ERBα proteostasis through the ubiquitin–proteasome system is an appealing cardioprotective strategy. Our data support the timed use of clinically approved cardiotonic steroids in prophylactic cardioprotection.

International audience; Multiple Sclerosis (MS) is an autoimmune demyelinating and neurodegenerative disease of the central nervous system (CNS). Current management strategies suppress or modulate immune function, all with consequences and known side effects. They demonstrate a high level of success in limiting new relapses. However, the neurodegenerative process still affects both grey and white matter in the central nervous system. The sigma1 (S1R) ligand-regulated chaperone is implicated in many biological processes in various CNS-targeted diseases, acting on neural plasticity, myelination and neuroinflammation. Among the proteins involved in MS, S1R has therefore emerged as a promising new target. Standard and robust methods have been adopted to analyze the adsorption, distribution, metabolism, excretion (ADME) properties, safety pharmacology and toxicology of a previously synthetized simple benzamide-derived compound with nanomolar affinity for S1R, high selectivity, no cytotoxicity and good metabolic stability. The compound was also characterized as an agonist based on well-validated assays prior to in vivo investigations. Interestingly, we found that the oral administration of this compound resulted in an overall significant reduction in clinical progression in an MS experimental model. This effect is mediated through S1R action. Our results further suggest the potential use of this compound in the treatment of MS.

International audience; Sensitive and selective detection of biomarkers in serum in a short time has a significant impact on health. The enormous clinical importance of developing reliable methods and devices for testing serum levels of cardiac troponin I (cTnI), which are directly correlated to acute myocardial infarction (AMI), has spurred an unmatched race among researchers for the development of highly sensitive and cost-effective sensing formats to be able to differentiate patients with early onset of cardiac injury from healthy individuals with a mean cTnI level of 26 pg mL-1. Electronic- and electrochemical-based detection schemes allow for fast and quantitative detection not otherwise possible at the point of care. Such approaches rely largely on voltammetric and field-effect-based readouts. Here, we systematically investigate electric and electrochemical point-of-care sensors for the detection of cTnI in serum samples by using the same surface receptors, cTnI aptamer-functionalized CVD graphene-coated interdigated gold electrodes. The analytical performances of both sensors are comparable with a limit of detection (LoD) of 5.7 ± 0.6 pg mL-1(electrochemical) and 3.3 ± 1.2 pg mL-1 (electric). However, both sensors exhibit different equilibrium dissociation constant (KD) values between the aptamer-linked surface receptor and the cTnI analyte, being 160 pg mL-1 for the electrochemical and about three times lower for the electrical approach with KD = 51.4 pg mL-1. This difference is believed to be related to the use of a redox mediator in the electrochemical sensor for readout. The ability of the redox mediator to diffuse from the solution to the surface via the cTnI/aptamer interface is hindered, correlating to higher KD values. In contrast, the electric readout has the advantage of being label-free with a sensing limitation due to ionic strength effects, which can be limited using poly(ethylene) glycol surface ligands.

International audience; Background: Patients with metabolic syndrome (MetS) have an increased risk of atrial fibrillation (AF). Impaired Ca2+ homeostasis and mitochondrial dysfunction have emerged as an arrhythmogenic substrate in both patients and animal models of MetS. Whether impaired mitochondrial Ca2+ handling underlies AF associated with MetS remains poorly explored.Objectives: The aim of this study was to determine the initial mechanisms related to AF susceptibility and mitochondrial dysfunction encountered in metabolic cardiomyopathy.Methods: A total of 161 mice and 34 patients were studied. Mitochondrial Ca2+ and mitochondrial Ca2+ uniporter complex (MCUC) were investigated in right atrial tissue of patients with (n = 18) or without (n = 16) MetS and of C57Bl/6J mice fed with a high-fat sucrose diet (HFS) for 2 (n = 42) or 12 (n = 39) weeks. Susceptibility to AF was evaluated in isolated sinoatrial tissue and in vivo in mice.Results: Increased expression of the MICUs subunits of the MCUC (1.00 ± 0.33 AU vs 1.29 ± 0.23 AU; P = 0.034) was associated with impaired mitochondrial Ca2+ uptake in patients (168.7 ± 31.3 nmol/min/mg vs 127.3 ± 18.4 nmol/min/mg; P = 0.026) and HFS mice (0.10 ± 0.04 ΔF/F0 × ms-1 vs 0.06 ± 0.03 ΔF/F0 × ms-1; P = 0.0086, and 0.15 ± 0.07 ΔF/F0 × ms-1 vs 0.046 ± 0.03 ΔF/F0 × ms-1; P = 0.0076 in 2- and 12-week HFS mice, respectively). HFS mice elicited a 70% increased susceptibility to AF. The MCUC agonist kaempferol restored MCUC activity in vitro and abolished the occurrence of AF in HFS mice.Conclusions: Impaired MCUC activity and mitochondrial Ca2+ homeostasis from the early stage of metabolic cardiomyopathy in mice lead to AF. Given that similar defects in cardiac mitochondrial Ca2+ handling are present in MetS patients, the modulation of the MCUC activity represents an attractive antiarrhythmic strategy.

Aims To investigate the additional prognostic value of myocardial work (MW) parameters following acute myocardial infarction (AMI). Methods and results Between 2018 and 2020, 244 patients admitted in the cardiac intensive care unit in Lille University Hospital for AMI were included. One-month following AMI, comprehensive transthoracic echocardiography (TTE) was performed to assess parameters of myocardial function. Patients were then followed for major events (ME): cardiovascular death, heart failure, and unplanned coronary revascularization. At 1-month, half of the population was symptomatic (NYHA ≥ II), and medical therapy was almost optimized (angiotensin-converting enzyme inhibitor/angiotensin 2 receptor blocker in 95.5%, beta-blockers in 96.3%, DAPT in 94.7%, and statins in 97.1%). After a median follow-up of 681 (interquartile range: 538–840) days, ME occurred in 26 patients (10.7%). Patients presenting ME were older (65.5 ± 14.2 vs. 58.1 ± 12.1years, P = 0.005) with a higher prevalence of hypertension (65.4 vs. 36.2%, P = 0.004), more impaired left ventricular (LV) function as assessed by LV ejection fraction (P = 0.07), global longitudinal strain (P = 0.03), or MW parameters [P = 0.01 for global work efficiency (GWE)], and greater LV and left atrium dilatations (P = 0.06 for left ventricular end-diastolic volume index and P = 0.03 for left atrial volume index). After adjustment, GWE was the only TTE parameter independently associated with long-term occurrence of ME (P = 0.02). A GWE value Conclusion Lower GWE at 1 month after AMI is independently associated with higher ME rates. A GWE

International audience; Cardiovascular diseases result in millions of deaths around the globe, many of which could have been avoided if identified at an early stage. Preventive cardiovascular disease diagnostics plays a vital role reducing the critical fatality rate by allowing to take timely necessary precautions. Here, we demonstrate the exceptional properties of aptamer modified graphenebased FET (GFET) for cardiac troponin I (cTnI) specific sensing in different bodily fluids. Concentration-dependent measurements made with cardiac troponin I (cTnI) on an aptamer/polyethylene glycol (PEG) modified GFET exhibited real-time detection of cTnI from 1-400 pg mL-1 in 0.01× phosphate-buffered saline (PBS) solution. The sensor performance is within the clinical important window of 10 pg mL-1 to 500 pg mL-1 , allowing the differentiation between healthy, and people with low and high risk for myocardial infraction (AMI). Even more important is the very reproducible shift and neglectable leakage current of the individual IDSVGS-curves upon contact with cTnI solutions. To further evaluate the applicability of the developed point of care device for troponin I sensing in serum, samples of 15 patients with different troponin levels were analysed for their troponin I levels. The 15 patients were grouped

Summary Background Poor reproducibility in assessment of mitral regurgitation (MR) has been reported. Aim To investigate the robustness of echocardiographic MR assessment in 2019, based on improvements in technology and the skill of echocardiographists regarding MR quantification. Methods Reproducibility in parameters of MR severity and global rating were tested using transthoracic echocardiography in 25 consecutive patients independently analysed by 16 junior and senior cardiologists specialized in echocardiography (400 analyses per parameter). Results Overall interobserver agreement for mechanism definition, effective regurgitant orifice area (EROA) and regurgitant volume (RVol) was moderate, and was lower in secondary MR. Interobserver agreement was substantial for EROA [0.61, 95% confidence interval (CI) 0.45 − 0.75] and moderate for RVol with the PISA method (0.50, 95% CI 0.33 – 0.56) in senior physicians and was fair in junior physicians (0.33, 95% CI 0.19 – 0.51 and 0.36, 95% CI 0.36 – 0.43, respectively). Using a multiparametric approach, overall interobserver agreement for grading MR severity was fair (0.30), was slightly better in senior than in junior physicians (0.31 vs. 0.28, respectively) with substantial or almost perfect agreement more frequently observed in senior versus junior physicians (52% vs. 36%, respectively). Conclusion Reproducible transthoracic echocardiography MR quantification remains challenging in 2019, despite the expected high skills of echocardiographers regarding MR at the time of dedicated percutaneous intervention. The multiparametric approach does not entirely alleviate the substantial dispersion in measurement of MR severity parameters, whereas reader experience seems to partially address the issue. Our study emphasizes the continuing need for multimodality imaging and education in the evaluation of MR among cardiologists.

Background Pre-operative myocardial fibrosis and remodeling impact on outcomes after aortic valve replacement (AVR). We aimed at investigating the prognostic impact of preoperative electrocardiographic (ECG) markers of left ventricular (LV) myocardial damage, i.e. bundle branch block (BBB) and ECG strain pattern after (surgical or transcatheter) AVR for severe aortic stenosis (AS). Methods Between April 2008 and October 2017, we explored consecutive patients referred to our Heart Valve Clinic for first AVR for severe AS. Detailed pre-operative phenotyping and ECG analysis were performed. Patients were followed-up after AVR for major cardiac events (ME), i.e. cardiovascular death, cardiac hospitalization for acute heart failure and stroke. Results BBB and ECG strain were respectively observed in 13.5 and 21% of the 1122 patients included. These ECG markers identified a subgroup of older patients, with higher NYHA class and more advanced myocardial disease as detected by echocardiography, i.e. higher LV mass and lower LV ejection fraction, global longitudinal strain and integrated backscatter, than patients without ECG strain or BBB. ME occurred in 212 (18.6%) patients during a mean follow-up of 4.4 ± 1.5 years with higher incidence in case of ECG strain or BBB (HR 1.56, 95%CI 1.13–2.14, p = 0.006; HR 1.47, 95%CI 1.02–2.13, p = 0.04 respectively). The prognostic value of ECG strain remained significant after adjustment for age, diabetes and pre-operative LVEF. Conclusions Pre-operative ECG markers of myocardial damage identify a subgroup of AS patients at high risk of post-AVR cardiovascular complications irrespective of other prognostic factors and should help the multiparametric staging of cardiac damage to guide AVR.

International audience; AimsWe assessed reverse dipping influence on the risk of lower limb events in type 2 diabetic patients without peripheral arterial disease.MethodsPatients with type 2 diabetes addressed for cardiovascular risk stratification in our university hospital from 2008 to 2012 underwent 24 h blood pressure monitoring. Patients with a prior history of limb revascularization or with a stenosis > 50% of the legs were excluded. Reverse dipping was defined as a greater night-versus day-time systolic blood pressure. The endpoint was the first occurrence of lower limb revascularization or limb amputation. Hazard ratios (HRs) and 95% confidence intervals were calculated using the Cox model.ResultsTwo hundred and eighty-one patients were included. During a median follow-up of 9.4 [7.7–10.6] years, 20 lower limb events and 45 all-cause deaths were observed. Thirty-five patients were reverse dippers. The reverse dipping status was associated with lower limb events when considering all-cause death as a competitive risk, (HR 3.61 [1.16–11.2], P = 0.026). Reverse dipping, HbA1C and proteinuria were independently associated with lower limb outcome in a multivariable analysis (respectively HR 4.09 [1.29–12.9], P = 0.017, HR 1.30 [1.04–1.63], P = 0.022 and HR 1.06 [1.02–1.11], P = 0.001).ConclusionsReverse dipping status is independently associated with worse limb outcome in type 2 diabetic patients.

ObjectiveCurrent data regarding the impact of diabetes mellitus (DM) on cardiovascular mortality in patients with aortic stenosis (AS) are restricted to severe AS or aortic valve replacement (AVR) trials. We aimed to investigate cardiovascular mortality according to DM across the entire spectrum of outpatients with AS.MethodsBetween May 2016 and December 2017, patients with mild (peak aortic velocity=2.5–2.9 m/s), moderate (3–3.9 m/s) and severe (≥4 m/s) AS graded by echocardiography were included during outpatient cardiology visits in the Nord-Pas-de-Calais region in France and followed-up for modes of death between May 2018 and August 2020.ResultsAmong 2703 patients, 820 (30.3%) had DM, mean age was 76±10.8 years with 46.6% of women and a relatively high prevalence of underlying cardiovascular diseases. There were 200 cardiovascular deaths prior to AVR during the 2.1 years (IQR 1.4–2.7) follow-up period. In adjusted analyses, DM was significantly associated with cardiovascular mortality (HR=1.40, 95% CI 1.04 to 1.89; p=0.029). In mild or moderate AS, the cardiovascular mortality of patients with diabetes was similar to that of patients without diabetes. In severe AS, DM was associated with higher cardiovascular mortality (HR=2.65, 95% CI 1.50 to 4.68; p=0.001). This was almost exclusively related to a higher risk of death from heart failure (HR=2.61, 95% CI 1.15 to 5.92; p=0.022) and sudden death (HR=3.33, 95% CI 1.28 to 8.67; p=0.014).ConclusionThe effect of DM on cardiovascular mortality varied across AS severity. Despite no association between DM and outcomes in patients with mild/moderate AS, DM was strongly associated with death from heart failure and sudden death in patients with severe AS.

Aims To compare the clinical significance of exercise echocardiography (ExE) and cardiopulmonary exercise testing (CPX) in patients with ≥moderate primary mitral regurgitation (MR) and discrepancy between symptoms and MR severity. Methods and results Patients consulting for ≥moderate discordant primary MR prospectively underwent low (25 W) ExE, peak ExE, and CPX within 2 months in Lille and Rennes University Hospital. Patients with Class I recommendation for surgical MR correction were excluded. Changes in MR severity, systolic pulmonary artery pressure (SPAP), left ventricular ejection fraction (LVEF), and tricuspid annular plane systolic excursion were evaluated during ExE. Patients were followed for major events (ME): cardiovascular death, acute heart failure, or mitral valve surgery. Among 128 patients included, 22 presented mild-to-moderate, 61 moderate-to-severe, and 45 severe MR. Unlike MR variation, SPAP and LVEF were successfully assessed during ExE in most patients. Forty-one patients (32%) displayed reduced aerobic capacity (peak VO2 < 80% of predicted value) with cardiac limitation in 28 (68%) and muscular or respiratory limitation in the 13 others (32%). ME occurred in 61 patients (47.7%) during a mean follow-up of 27 ± 21 months. Twenty-five Watts SPAP [hazard ratio (HR) (95% confidence interval, CI) = 1.03 (1.01–1.06), P = 0.003] and reduced aerobic capacity [HR (95% CI) = 1.74 (1.03–2.95), P = 0.04] were independently predictive of ME, even after adjustment for MR severity. The cut-off of 55 mmHg for 25 W SPAP showed the best accuracy to predict ME (area under the curve = 0.60, P = 0.05). Conclusion In patients with ≥moderate primary MR and discordant symptoms, 25 W exercise pulmonary hypertension, defined as an SPAP ≥55 mmHg, and poor aerobic capacity during CPX are independently associated with adverse events.

Background and objective: Cardiac magnetic resonance (CMR) is a key tool for cardiac work-up. However, arrhythmia can be responsible for arrhythmia-related artifacts (ARA) and increased scan time using segmented sequences. The aim of this study is to evaluate the effect of cardiac arrhythmia on image quality in a comparison of a compressed sensing real-time (CSrt) cine sequence with the reference prospectively gated segmented balanced steady-state free precession (Cineref) technique regarding ARA. Methods: A total of 71 consecutive adult patients (41 males, mean age = 59.5 ± 20.1 years (95% CI: 54.7–64.2 years)) referred for CMR examination with concomitant irregular heart rate (defined by an RR interval coefficient of variation &gt, 10%) during scanning were prospectively enrolled. For each patient, two cine sequences were systematically acquired: first, the reference prospectively triggered multi-breath-hold Cineref sequence including a short-axis stack, one four-chamber slice, and a couple of two-chamber slices, second, an additional single breath-hold CSrt sequence providing the same slices as the reference technique. Two radiologists independently assessed ARA and image quality (overall, acquisition, and edge sharpness) for both techniques. Results: The mean heart rate was 71.8 ± 19.0 (SD) beat per minute (bpm) (95% CI: 67.4–76.3 bpm) and its coefficient of variation was 25.0 ± 9.4 (SD) % (95% CI: 22.8–27.2%). Acquisition was significantly faster with CSrt than with Cineref (Cineref: 556.7 ± 145.4 (SD) s (95% CI: 496.7–616.7 s), CSrt: 23.9 ± 7.9 (SD) s (95% CI: 20.6–27.1 s), p &lt, 0.0001). A total of 599 pairs of cine slices were evaluated (median: 8 (range: 6–14) slices per patient). The mean proportion of ARA-impaired slices per patient was 85.9 ± 22.7 (SD) % using Cineref, but this was figure was zero using CSrt (p &lt, 0.0001). The European CMR registry artifact score was lower with CSrt (median: 1 (range: 0–5)) than with Cineref (median: 3 (range: 0–3), 0.0001). Subjective image quality was higher in CSrt than in Cineref (median: 3 (range: 1–3) versus 2 (range: 1–4), respectively, 0.0001). In line, edge sharpness was higher on CSrt cine than on Cineref images (0.054 ± 0.016 pixel−1 (95% CI: 0.050–0.057 pixel−1) versus 0.042 ± 0.022 pixel−1 (95% CI: 0.037–0.047 pixel−1), respectively, p = 0.0001). Conclusion: Compressed sensing real-time cine drastically reduces arrhythmia-related artifacts and thus improves cine image quality in patients with arrhythmia.

Both pre-operative planning and periprocedural guidance of transcatheter mitral valve replacement (TMVR) are based on the independent analysis of transesophageal echocardiography (echo) and computed tomography scanner (CT) images ([1][1]). Echo-CT fusion (Vivid E95, GE Healthcare, Horten, Norway) ([

Patients with aortic stenosis (AS) and prior mediastinal radiotherapy (XRT) represent a challenging group ([1–3][1]). The detrimental effects due to the pressure overload associated with AS may be compounded by the presence of radiation heart disease. Echocardiographic speckle-tracking strain

Despite improvements in organ preservation techniques and efforts to minimize the duration of cold ischemia, ischemia–reperfusion (IR) injury remains associated with poor graft function and long-term survival in kidney transplantation. We recently demonstrated a clinically significant day-time variation in myocardial tolerance to IR, transcriptionally orchestrated by the circadian clock. Patient and graft post-transplant survival were studied in a cohort of 10,291 patients first transplanted between 2006 and 2017 to test whether kidney graft tolerance to IR depends on the time-of-the-day of clamping/declamping, and thus impacts graft and patient survival. Post-transplant 1- and 3-year survival decreased with increasing ischemia duration. Time-of-the-day of clamping did not influence outcomes. However, night-time (vs. day-time) declamping was associated with a significantly worse post-transplant survival. After adjustment for other predictors, night-time (vs. day-time) declamping remained associated with a worse 1-year (HR= 1.26 (1.08–1.47), p = 0.0028 by Cox multivariable analysis) and 3-year (HR= 1.14 (1.02–1.27), p = 0.021) outcome. Interestingly, the deleterious impact of prolonged ischemia time (&gt, 15 h) was partially compensated by day-time (vs. night-time) declamping. Compared to night-time declamping, day-time declamping was associated with a better prognosis of kidney transplantation despite a longer duration of cold ischemia.

International audience; Peroxisome proliferator-activated receptor-α (PPARα), PPARδ and PPARγ are transcription factors that regulate gene expression following ligand activation. PPARα increases cellular fatty acid uptake, esterification and trafficking and regulates lipoprotein metabolism genes. PPARδ stimulates lipid and glucose utilization by increasing mitochondrial function and fatty acid desaturation pathways. By contrast, PPARγ promotes fatty acid uptake, triglyceride formation and storage in lipid droplets, thereby improving insulin sensitivity and glucose metabolism. PPARs also exert anti-atherogenic and anti-inflammatory effects on the vascular wall and immune cells. Clinically, PPARγ activation by glitazones and PPARα activation by fibrates improve insulin resistance and dyslipidaemia, respectively. PPARs are also physiological master switches in the heart, steering cardiac energy metabolism in cardiomyocytes, thereby affecting pathological heart failure and diabetic cardiomyopathy. Novel PPAR agonists in clinical development are providing new opportunities in the management of metabolic and cardiovascular diseases.

Background and objective: To evaluate the reliability of compressed-sensing (CS) real-time single-breath-hold cine imaging for quantification of right ventricular (RV) function and volumes in congenital heart disease (CHD) patients in comparison with the standard multi-breath-hold technique. Methods: Sixty-one consecutive CHD patients (mean age = 22.2 ± 9.0 (SD) years) were prospectively evaluated during either the initial work-up or after repair. For each patient, two series of cine images were acquired: first, the reference segmented multi-breath-hold steady-state free-precession sequence (SSFPref), including a short-axis stack, one four-chamber slice, and one long-axis slice, then, an additional real-time compressed-sensing single-breath-hold sequence (CSrt) providing the same slices. Two radiologists independently assessed the image quality and RV volumes for both techniques, which were compared using the Wilcoxon test and paired Student’s t test, Bland–Altman, and linear regression analyses. The visualization of wall-motion disorders and tricuspid-regurgitation-related signal voids were also analyzed. Results: The mean acquisition time for CSrt was 22.4 ± 6.2 (SD) s (95% CI: 20.8–23.9 s) versus 442.2 ± 89.9 (SD) s (95% CI: 419.2–465.2 s) for SSFPref (p &lt, 0.001). The image quality of CSrt was diagnostic in all examinations and was mostly rated as good (n = 49/61, 80.3%). There was a high correlation between SSFPref and CSrt images regarding RV ejection fraction (49.8 ± 7.8 (SD)% (95% CI: 47.8–51.8%) versus 48.7 ± 8.6 (SD)% (95% CI: 46.5–50.9%), respectively, r = 0.94) and RV end-diastolic volume (192.9 ± 60.1 (SD) mL (95% CI: 177.5–208.3 mL) versus 194.9 ± 62.1 (SD) mL (95% CI: 179.0–210.8 mL), respectively, r = 0.98). In CSrt images, tricuspid-regurgitation and wall-motion disorder visualization was good (area under receiver operating characteristic curve (AUC) = 0.87) and excellent (AUC = 1), respectively. Conclusions: Compressed-sensing real-time cine imaging enables, in one breath hold, an accurate assessment of RV function and volumes in CHD patients in comparison with standard SSFPref, allowing a substantial improvement in time efficiency.

Funding Acknowledgements Type of funding sources: None. Background Aortic regurgitation (AR) quantification still remains challenging and requires an integrated approach. AR mechanism is one key parameter to take into account to assess its severity and repairability, and thus help to guide surgical decision. Although Cardiac Magnetic Resonance (CMR) has a growing interest in AR quantification, its performance to identify aortic AR mechanism has never been studied. Purpose We intended to define CMR Performance in this setting, by using echocardiography as reference. Methods AR mechanism was systematically evaluated in sixty-seven patients (81% male, mean age 46 ± 20 years) with chronic AR using CMR, and compared to transthoracic (TTE) and transesophageal (TEE) echocardiography as gold standard. AR were categorized as follows: type 1, aortic dilatation; type 2, Cusp prolapse; type 3, restrictive cusp motion. Jet direction, number of cusps and calcification (1 = no calcification, 2 = spots, 3 = big calcification interfering with cusp motion and 4 = Extensive with restricted cusp motion) were also evaluated. Results At TTE/TEE, mechanisms of AR were type 1 in 56 (83.5%), type 2 in 33 (49.2%), type 3 in 24 (35%). Agreement between TTE/TEE and CMR was modest, with respectively 74.6% (k= 0.4), 79.1% (k = 0.58) and 74.6% (k = 0.44). Bicuspid aortic valve was found in 44 (65.7%) patients at TTE/TEE, agreement with CMR was excellent, 98.5% (k = 0.97). Jet was directed to the mitral valve in 42 (62.7%), at the inter ventricular septum in 12 (17.9%), and central in 13 (19.4%). Agreement with CMR was correct, respectively 80% (k = 0,6), 88% (k = 0.62) and 83.5% (K= 0.52). Calcification extension was 1 in 26 (38.8%), 2 in 25 (37.3%), 3 in 11 (16.4%) and 4 in 5 (7.5%). Agreement with CMR was poor, 44.7% (K= 0.28). Conclusion Accuracy between CMR and TTE/TEE to evaluate chronic AR mechanism and repairability was modest, with lower performance to define calcification extension. Abstract Figure. AR classification TTE/TEE vs CMR

Funding Acknowledgements Type of funding sources: None. Background. 3-dimensional transoesophageal echocardiography (3D-TEE) is frequently used as an initial screening tool in the evaluation of patients who are candidates to Transcatheter Mitral Valve Replacement (TMVR). However, little is known about the imaging correlation with the gold-standard computed tomography (CT) imaging. We aimed at testing the quantitative differences between these two modalities and finding the best 3D-TEE parameters for TMVR screening. Methods. We included 57 patients referred to our Heart Valve Clinic for TMVR with prostheses specifically designed for the mitral valve. Mitral annulus (MA) analyses were performed using commercially available software in 3D-TEE and CT. Results. 3D-TEE was feasible in 52 patients (91%). Although 3D-TEE measurements were slightly lower than in CT, both measurements of projected MA area and perimeter showed excellent correlation with small differences between the two modalities (r = 0.88 and r = 0.92 respectively, p Abstract Figure.

Objectives Assessment of the adaptive immune response against severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) is crucial for studying long‐term immunity and vaccine strategies. We quantified IFNγ‐secreting T cells reactive against the main viral SARS‐CoV‐2 antigens using a standardised enzyme‐linked immunospot assay (ELISpot). Methods Overlapping peptide pools built from the sequences of M, N and S viral proteins and a mix (MNS) were used as antigens. Using IFNγ T‐CoV‐Spot assay, we assessed T‐cell and antibody responses in mild, moderate and severe SARS‐CoV‐2 patients and in control samples collected before the outbreak. Results Specific T cells were assessed in 60 consecutive patients (mild, n = 26; moderate, n = 10; and severe patients, n = 24) during their follow‐up (median time from symptom onset [interquartile range]: 36 days [28;53]). T cells against M, N and S peptide pools were detected in n = 60 (100%), n = 56 (93.3%), n = 55 patients (91.7%), respectively. Using the MNS mix, IFNγ T‐CoV‐Spot assay showed a specificity of 96.7% (95% CI, 88.5–99.6%) and a specificity of 90.3% (75.2–98.0%). The frequency of reactive T cells observed with M, S and MNS mix pools correlated with severity and with levels of anti‐S1 and anti‐RBD serum antibodies. Conclusion IFNγ T‐CoV‐Spot assay is a reliable method to explore specific T cells in large cohorts of patients. This test may become a useful tool to assess the long‐lived memory T‐cell response after vaccination. Our study demonstrates that SARS‐CoV‐2 patients developing a severe disease achieve a higher adaptive immune response., We quantified IFNg‐secreting T cells reactive against the M, N and S viral SARS‐CoV‐2 proteins using a standardized enzyme‐linked immunospot assay in 60 patients. The frequency of reactive T cells correlated with severity, and with levels of anti‐S1 and anti‐RBD (receptor binding domain) serum antibodies, demonstrating a higher adaptive immune response after developing a more severe disease. IFNg T‐CoV‐Spot assay may also become a useful tool to assess the long‐lived memory T cell response after vaccination.

International audience; Background: Three-dimensional (3D) transesophageal echocardiographic (TEE) imaging is frequently used as an initial screening tool in the evaluation of patients who are candidates for transcatheter mitral valve replacement (TMVR). However, little is known about the imaging correlation with the gold standard, computed tomographic (CT) imaging. The aims of this study were to test the quantitative differences between these two modalities and to determine the best 3D TEE parameters for TMVR screening.Methods: Fifty-seven patients referred to the heart valve clinic for TMVR with prostheses specifically designed for the mitral valve were included. Mitral annular (MA) analyses were performed using commercially available software on 3D TEE and CT imaging.Results: Three-dimensional TEE imaging was feasible in 52 patients (91%). Although 3D TEE measurements were slightly lower than those obtained on CT imaging, measurements of both projected MA area and perimeter showed excellent correlations, with small differences between the two modalities (r = 0.88 and r = 0.92, respectively, P < .0001). Correlations were significant but lower for MA diameters (r = 0.68-0.72, P < .0001) and mitroaortic angle (r = 0.53, P = .0001). Receiver operating characteristic curve analyses showed that 3D TEE imaging had a good ability to predict TMVR screening success, defined by constructors on the basis of CT measurements, with ranges of 12.9 to 15 cm2 for MA area (area under the curve [AUC] = 0.88-0.91, P < .0001), 128 to 139 mm for MA perimeter (AUC = 0.85-0.91, P < .0001), 35 to 39 mm for anteroposterior diameter (AUC = 0.79-0.84, P < .0001), and 37 to 42 mm for posteromedial-anterolateral diameter (AUC = 0.81-0.89, P < .0001).Conclusions: Three-dimensional TEE measurements of MA dimensions display strong correlations with CT measurements in patients undergoing TMVR screening. Three-dimensional TEE imaging should be proposed as a reasonable alternative to CT imaging in this vulnerable population.

International audience; BACKGROUND: Although recommendations encourage daily moderate activities in post aortic dissection, very little data exists regarding cardiopulmonary exercise testing (CPET) to personalize those patient's physical rehabilitation and assess their cardiovascular prognosis.METHODS: We aimed at testing the prognostic insight of CPET regarding aortic and cardiovascular events by exploring a prospective cohort of patients followed-up after acute aortic dissection.METHODS: Patients referred to our department after an acute (type A or B) aortic dissection were prospectively included in a cohort between September 2012 and October 2017. CPET was performed once optimal blood pressure control was obtained. Clinical follow-up was done after CPET for new aortic event and major cardio-vascular events (MCE) not directly related to the aorta.RESULTS: Among the 165 patients who underwent CPET, no adverse event was observed during exercise testing. Peak oxygen pulse was 1.46(1.22-1.84) mlO2/beat, that is, 97 (83-113) % of its predicted value, suggesting cardiac exercise limitation in a population under beta blockers (92% of the population). During a follow-up of 39(20-51) months from CPET, 42 aortic event recurrences and 22 MCE not related to aorta occurred. Low peak oxygen pulse (

Purpose To evaluate the reliability of a real-time compressed sensing (CS) cine sequence for the detection of left ventricular wall motion disorders after myocardial infarction in comparison with the reference steady-state free precession cine sequence. Materials and Methods One hundred consecutive adult patients referred for either initial work-up or follow-up by cardiac magnetic resonance (CMR) in the context of myocardial infarction were prospectively included. There were 77 men and 23 women with a mean age of 63.12 ± 11.3 (SD) years (range: 29–89 years). Each patient underwent the reference segmented multi-breath-hold steady-state free precession cine sequence including one short-axis stack and both vertical and horizontal long-axis slices (SSFPref) and the CS real-time single-breath-hold evaluated sequence (CSrt) providing the same slices. Wall motion disorders were independently and blindly assessed with both sequences by two radiologists, using the American Heart Association left ventricle segmentation. Paired Wilcoxon signed-rank test was used to search for differences in wall motion disorders conspicuity between both sequences and receiver operating characteristic curve (ROC) analysis was performed to assess the diagnosis performance of CSrt sequence using SSFPref as the reference method. Results Each patient had at least one cardiac segment with wall motion abnormality on SSFPref and CSrt images. The 1700 segments analyzed with SSFPref were classified as normokinetic (360/1700; 21.2%), hypokinetic (783/1700; 46.1%), akinetic (526/1700; 30.9%) or dyskinetic (31/1700; 1.8%). Sensitivity and specificity of the CS sequence were 99.6% (95% CI: 99.1–99.9%) and 99.7% (95% CI: 98.5–100%), respectively. Area under ROC of CSrt diagnosis performance was 0.997 (95% CI: 0.993–0.999). Conclusion CS real-time cine imaging significantly reduces acquisition time without compromising the conspicuity of left ventricular -wall motion disorders in the context of myocardial infarction.