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International audience; Background: Estimated plasma volume status (ePVS) has diagnostic and prognostic value in patients with heart failure (HF). However, it remains unclear which congestion markers (i.e., biological, imaging and hemodynamic markers) are preferentially associated with ePVS. In addition, there is evidence of sex differences in both the hematopoietic process and myocardial structure/function.Method and results: Patients with significant dyspnea (NYHA≥2) underwent echocardiography and lung ultrasound within four hours prior to cardiac catheterization. Patients were divided according to tertiles based on sex-specific ePVS thresholds calculated from hemoglobin and hematocrit measurements using Duarte’s formula.Among the 78 included patients (median age 74.5 years; males 69.2%; HF 48.7%), median ePVS was 4.1 (percentile25-75=3.7-4.9) ml/g in males (N=54) and 4.8 (4.4-5.3) ml/g in females (N=24). Patients with the highest ePVS had more frequently HF, higher NT-proBNP, larger left atrial volume and higher E/e’ (all p-values0.10). In multivariable analysis, higher E/e’ and lower diastolic blood pressure were significantly associated with increased ePVS. The association between ePVS and congestion variables was not sex-dependent except for left ventricular end-diastolic pressure, which was only correlated with ePVS in females (Spearman Rho=0.53, p

Resume L’hypertension arterielle pulmonaire (HTAP) est une pathologie rare, caracterisee par une augmentation des resistances vasculaires pulmonaires. Parmi les multiples etiologies d’HTAP, on retrouve les HTAP induites par la prise de medicaments, principalement representes par les traitements anorexigenes. Nous rapportons les cas de quatre patients ayant developpe une HTAP au cours d’un traitement par leflunomide, molecule prescrite dans le cadre d’une polyarthrite rhumatoide, d’un rhumatisme psoriasique ou d’une connectivite indifferenciee. Les quatre patients consultaient pour une dyspnee d’installation progressive (stade II a IV de la NYHA au moment du diagnostic) ; l’examen clinique retrouvait des signes cliniques d’insuffisance cardiaque, motivant la realisation d’une echographie cardiaque. Des signes echographiques evocateurs d’HTAP faisaient realiser un catheterisme cardiaque droit, retrouvant une hypertension pulmonaire pre-capillaire (pression arterielle pulmonaire moyenne superieure a 25 mmHg et une pression arterielle pulmonaire d’occlusion inferieure a 15 mmHg). Le bilan etiologique d’hypertension pulmonaire pre-capillaire etait realise tel que preconise par les recommandations internationales ; la realisation d’une scintigraphie de ventilation-perfusion et d’un angioscanner thoracique permettait d’exclure les diagnostics d’hypertension pulmonaire post-embolique chronique ou en rapport avec une maladie respiratoire chronique. Le diagnostic d’HTAP etait alors retenu et les explorations realisees a visee etiologique etaient negatives. L’imputabilite du leflunomide etait finalement retenue. Le traitement incrimine etait arrete pour les quatre patients, et trois d’entre eux ont recu un traitement specifique de l’HTAP. L’evolution clinique et/ou hemodynamique etait favorable pour l’ensemble des patients. Ces quatre cas ont ete declares au centre local de pharmacovigilance, permettant de retenir un signal faible. Cela a conduit a la modification de la monographie du leflunomide en ajoutant « hypertension pulmonaire » a la rubrique « effets indesirables » et « de rares cas d’hypertension pulmonaire ont ete rapportes pendant un traitement par leflunomide » a la rubrique « mises en garde ».

International audience; Aims - The current algorithm in transthoracic echocardiography (TTE) proposed in the 2016 ASE/EACVI recommendation for the estimation of left ventricular filling pressure (LVFP) is quite complex and time-consuming. B-lines, in lung ultrasonography (LUS), could constitute an interesting tool for LVFP evaluation in clinical practice, although data regarding their association with invasive haemodynamics are lacking. The purpose of this study was to explore the diagnostic accuracy of B-lines in identifying elevated left ventricular end-diastolic pressure (LVEDP). Method and results - 81 adults with significant dyspnoea (NYHA ≥ 2) were prospectively analyzed by LUS in four areas in each hemithorax and a complete TTE within four hours prior to coronary angiography. Twenty-eight patients had elevated LVEDP. Clinical variables yielded a C-index of 79% to identify elevated LVEDP. The number of total B-lines was higher in the elevated LVEDP group (1.0vs17.0, p

International audience; Aims Secondary tricuspid regurgitation (STR) is commonly found in patients with aortic stenosis and is associated with increased morbidity. The study sought to evaluate the prevalence of pre-operative STR and its progression after surgical aortic valve replacement (SAVR) or transcatheter aortic valve implantation (TAVI). Also, it sought to analyse the predictors of post-operative changes in STR. Methods and results We prospectively evaluated 116 patients (aged 75.1 ± 9.8 years, predominantly male) who undergo SAVR or TAVI for severe aortic stenosis (AS) from September 2013 to April 2015. Patients with associated valve disease requiring intervention, significant coronary artery disease or left ventricular ejection fraction (LVEF) 40 mm was the only echocardiographic predictor of significant postoperative TR (relative risk (RR) = 2.12 [1.26-3.54], P = 0.004). Right heart function and size were not independent predictors. Conclusion Significant TR was present pre-operatively in 11.1% of patients. Post-operative progression was observed in 26.7% of patients. Only tricuspid annulus size >40 mm was an independent echocardiographic predictor of moderate to severe TR at the 1-year follow-up. © 2017 The Author.

Summary Background The relationship between electrical and mechanical indices of cardiac dyssynchronization in systolic heart failure (HF) remains poorly understood. Objectives We examined retrospectively this relationship by using the daily practice tools in cardiology in recipients of cardiac resynchronization therapy (CRT) systems. Methods We studied 119 consecutive patients in sinus rhythm and QRS ≥ 120 ms (mean: 160 ± 17 ms) undergoing CRT device implantation. P wave duration, PR, e PR (end of P wave to QRS onset), QT, RR–QT, JT and QRS axis and morphology were putative predictors of atrioventricular (diastolic filling time [DFT]/RR), interventricular mechanical dyssynchrony (IVMD) and left intraventricular mechanical dyssynchrony (left ventricular pre-ejection interval [PEI] and other measures) assessed by transthoracic echocardiography (TTE). Correlations between TTE and electrocardiographic measurements were examined by linear regression. Results Statistically significant but relatively weak correlations were found between heart rate ( r = −0.5), JT ( r = 0.3), QT ( r = 0.3), RR–QT intervals ( r = 0.5) and DFT/RR, though not with PR and QRS intervals. Weak correlations were found between: (a) QRS ( r = 0.3) and QT interval ( r = 0.3) and (b) IVMD > 40 ms; and between (a) e PR ( r = −0.2), QRS ( r = 0.4), QT interval ( r = 0.3) and (b) LVPEI, though not with other indices of intraventricular dyssynchrony. Conclusions The correlations between electrical and the evaluated mechanical indices of cardiac dyssynchrony were generally weak in heart failure candidates for CRT. These data may help to explain the discordance between electrocardiographic and echocardiographic criteria of ventricular dyssynchrony in predicting the effect of CRT.

Background Cardiac resynchronization therapy (CRT) improves left ventricular (LV) function and induces LV remodeling, and it is an established therapy for advanced heart failure with prolonged QRS duration. One third of patients will not benefit from this invasive therapy. Objective The purpose of this study was to evaluate whether left atrial (LA) strain imaging (e) parameters could help in predicting the response in terms of LV reverse remodeling after CRT. Methods A total of 79 patients who underwent CRT were evaluated with echography before implantation. LA function and LV function were assessed with M-mode, 2-dimensional echocardiography, Doppler, tissue Doppler velocity, and e. LV reverse remodeling was defined as a >15% reduction in LV end-systolic volume. Results At 6 months, 54 patients (68%) were responders to CRT. In multivariable logistic regression, LA systolic peak of strain rate (SRA) (odds ratio [OR} 10.5, 95% confidence interval [CI] 1.76–62.1, P = .01), left bundle branch block (OR 6.8, 95% CI 1.06–43.9, P = .04), ischemic cardiomyopathy (OR 3.93, 95% CI 1.07–14.4, P = .04), and LV preejection index (OR 1.03, 95% CI 1.01–1.05, P = .01) were associated with CRT response. With an SRA cutoff of –0.75%, the negative predictive value for predicting CRT response was 0.62. Conclusion This study demonstrated the possible relevance of assessing LA function before CRT. SRA appeared to be a good predictor of CRT response. Integrating this LA function analysis into the multivariable assessment of patient candidates for CRT should be considered.

International audience; Glycation is both a physiological and pathological process which mainly affects proteins, nucleic acids and lipids. Exogenous and endogenous glycation produces deleterious reactions that take place principally in the extracellular matrix environment or within the cell cytosol and organelles. Advanced glycation end product (AGE) formation begins by the non-enzymatic glycation of free amino groups by sugars and aldehydes which leads to a succession of rearrangements of intermediate compounds and ultimately to irreversibly bound products known as AGEs. Epigenetic factors, oxidative stress, UV and nutrition are important causes of the accumulation of chemically and structurally different AGEs with various biological reactivities. Cross-linked proteins, deriving from the glycation process, present both an altered structure and function. Nucleotides and lipids are particularly vulnerable targets which can in turn favor DNA mutation or a decrease in cell membrane integrity and associated biological pathways respectively. In mitochondria, the consequences of glycation can alter bioenergy production. Under physiological conditions, anti-glycation defenses are sufficient, with proteasomes preventing accumulation of glycated proteins, while lipid turnover clears glycated products and nucleotide excision repair removes glycated nucleotides. If this does not occur, glycation damage accumulates, and pathologies may develop. Glycation-induced biological products are known to be mainly associated with aging, neurodegenerative disorders, diabetes and its complications, atherosclerosis, renal failure, immunological changes, retinopathy, skin photoaging, osteoporosis, and progression of some tumors.

International audience; Pulmonary arterial hypertension (PAH) is a rare disorder that can be drug-induced, mostly following treatment by appetite-suppressant drugs. We report four cases of patients who developed PAH following a treatment by leflunomide for rheumatoid arthritis, psoriatic arthritis or undetermined connective tissue disease. All patients described a progressive dyspnea from grade II to IV of NYHA classification; clinical examination found signs of heart failure. PAH was finally diagnosed and confirmed by right heart catheterisation. Haemodynamic explorations found pre-capillary pulmonary hypertension with mean pulmonary arterial pressure above 25mmHg, and pulmonary capillary wedge pressure under 15mmHg. Explorations of this pre-capillary pulmonary hypertension were conducted according to international guidelines: pulmonary or chronic thromboembolic aetiologies were excluded after ventilation/perfusion lung scan and high-resolution computed tomography. All other etiologic explorations were negative. Imputability of leflunomide was finally retained. Leflunomide was stopped for all patients; three of them received specific PAH treatments. A favourable clinical and/or haemodynamic evolution was observed for all patients. The conclusions of the investigations conducted by our pharmacovigilance centre were communicated to the European Medicines Agency, leading to the addition of "pulmonary hypertension" in the paragraph "special warning and precautions of use" of the package leaflet of leflunomide.

International audience; The L2ANDS2 score was previously found to be able to assess the probability of left ventricular (LV) remodeling. We sought to evaluate this score in terms of clinical outcomes: 275 patients with heart failure, from 2 centers, implanted with a cardiac resynchronization therapy (CRT) device were followed at least 2 years after implantation. Baseline clinical, electrocardiographic, and echocardiographic characteristics including left bundle branch block, age >70 years, nonischemic etiology, LV end-diastolic diameter

Summary Background Left bundle branch block (LBBB) induces mechanical dyssynchrony that may lead to left ventricular systolic dysfunction. Aims To evaluate the incidence, predictors and clinical impact of new LBBB in patients undergoing surgical aortic valve replacement (SAVR). Methods After exclusion of patients with pre-existing LBBB, a previous pacemaker or a paced rhythm at hospital discharge, 547 consecutive patients undergoing SAVR were included. All-cause death, cardiovascular death and the combined outcome of all-cause death or a first heart failure event were assessed at 3 months and 1 year. Patients with and without new LBBB were compared. Results New LBBB occurred in 4.6% of patients after SAVR (compared with 16.4% of patients treated by transcatheter aortic valve implantation during the study period). Previous valve surgery and an immediate postoperative paced rhythm were independent predictors of new LBBB. At 1-year follow-up, there were no significant differences in all-cause death, cardiovascular death, or the combined outcome of all-cause death or a first heart failure event between patients with and without new LBBB. However, new LBBB was associated with a trend towards functional deterioration and more heart failure events at 1 year. Conclusion At 1-year follow-up, new LBBB did not have a significant impact on clinical outcome, but was associated with worse functional status and more heart failure events.

Summary Background Left atrial (LA) enlargement is frequent in patients with aortic stenosis (AS), yet its determinants and prognostic implications are poorly understood. Aims To identify the echocardiographic variables associated with increased LA volume index (LAVI), and test the prognostic value of LAVI in AS. Methods We prospectively included 715 patients with AS in sinus rhythm at enrolment. Echocardiography was performed at baseline. Median follow-up was 22.0 (9–34) months. Patients were divided into two groups according to the best cut-off for event prediction during follow-up (45 mL/m 2 ). Results Compared with LAVI 2 , patients with LAVI ≥ 45 mL/m 2 had a lower stroke volume, cardiac output and left ventricular (LV) ejection fraction, greater LV volumes and mass and higher filling pressures. By linear regression, LAVI was best correlated with E wave mitral velocity ( r = 0.34), E/A ratio ( r = 0.34), E/e’ ratio ( r = 0.28), indexed LV mass ( r = 0.29), systolic pulmonary artery pressure ( r = 0.34) and LV longitudinal strain ( r = –0.28). Multivariable analysis confirmed the independent association of LAVI with age ( P P = 0.04), indexed LV mass ( P P = 0.007), LV end-diastolic volume ( P = 0.001), E/A ratio ( P P 2 was independently predictive of the combined endpoint of cardiovascular death or hospitalization for heart failure (adjusted hazard ratio 1.69, 95% confidence interval 1.04–2.73). Conclusion LA enlargement is correlated with AS severity, but also with variables reflecting LV systolic and diastolic dysfunction. Further studies are needed to investigate the outcome implication of LA enlargement in patients with AS.

International audience; Aims The aim of this article is to assess the left atrial (LA) reservoir function in patients with severe aortic stenosis (AS) and to evaluate its impact on the recurrence of major adverse cardiac events (MACEs).Methods and results About 128 patients (mean age 79 ± 9 years) with severe AS were included in the study. Global peak LA strain (PLAS) measured by two-dimensional speckle-tracking echocardiography (STE) during left ventricular (LV) systole represented the LA reservoir function. Overall death, hospitalization for cardiac cause, and worsening heart failure were defined as MACEs. With respect to the values observed in a control group of 20 healthy patients, PLAS resulted significantly reduced in AS. According to the multivariate linear regression analysis, LV global longitudinal strain, mitral E/e′ ratio, and systolic pulmonary arterial pressure (sPAP) were the best correlates to PLAS. During follow-up, the predefined MACEs occurred in 39 patients. According to the multivariate Cox regression analysis, a PLAS \textless21% was a significant predictor of MACEs [hazard ratio (HR) 2.88, P = 0.04], as was coronary artery disease (HR 2.68, P = 0.004) and the New York Heart Association functional class (HR 2.08, P = 0.03).Conclusion In patients with severe AS, a global PLAS \textless21% is an independent predictor of prognosis. Given the combined influence of LV diastolic and systolic function and of LA performance on sPAP, the decline of PLAS might be considered a marker of global myocardial impairment in AS. Further studies are needed to confirm the critical role of LA relaxation in prognosis and to validate its relevance in routine clinical practice

Aim B-lines, in lung ultrasound (LUS), could constitute an interesting tool for LVFP evaluation in clinical practice, but data regarding their association with invasive hemodynamics are lacking. The purpose of this study is to explore the diagnostic accuracy of B-lines to identify elevated left ventricular end-diastolic pressure (LVEDP). Method In total, 81 adults (mean age 75 years old) with significant dyspnea (NYHA 2) were prospectively analyzed by LUS, with the same probe than transthoracic echocardiography (TTE), in four areas in each hemithorax [detailed method in Fig. 1 . Panel 1: The four explored areas on the right hemithorax; Panel 2: Example of a freezed loop of lung ultrasound with B-lines; Panel 3: The different cut-offs analysed. A: one bilateral positive zone (defined by ≥ 3 B-lines in the same zone); B: two bilateral positive zones; C: Simplified B-lines count: sum of all B-lines in the eight zones using two different cut-offs: ≥ 3 or ≥ 8 B-lines] and complete TTE within four hours before a coronary angiography. Results ( Table 1 ): 28 patients had elevated LVEDP. A clinical model, including age, dyspnea NYHA3 and heart failure signs, had a C-index of 79% to identify elevated LVEDP. Total B-lines number was higher in the elevated LVEDP group (1.0 vs.17.0, P Conclusion This study demonstrates the important diagnostic capacity of B-lines to identify elevated LVEDP, which appears superior to the one of classical echocardiographic strategies. This tool should be considered in a multi-parametric approach of patients with heart failure.

International audience; Background Left ventricular (LV) pressure-strain loops (PSLs) have been recently validated as a non-invasive index of myocardial performance. Aim of the present study is to compare average cardiac work (avgCW), positive work (avgPW), negative work (avgNW) and work efficiency (WE) in normal subjects (NOR) and in cardiac resynchronization therapy candidates (CRT). Methods we included in this study 20 NOR and 61 CRT patients (mean LVEF, GLS and QRS duration: 64±5 vs 27±5%, -23±2 vs –8±3%, 71±21 vs 170±17 msec; respectively, all p

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International audience; Aims Systolic pulmonary artery pressure (sPAP) is a well-known outcome predictor in patients with valvular heart disease. Limited data are available regarding the evaluation of right ventricular (RV) performance, particularly in patients with aortic stenosis (AS). The aim of this study was to evaluate the prevalence, determinants, and prognostic significance of RV dysfunction in severe AS independently from the strategy of treatment chosen. Methods and results Two hundred patients (mean age: 79.9 ± 8.8 years) with severe AS underwent two-dimensional and speckle tracking echocardiography for the evaluation of left ventricular (LV) and RV functions, aortic valve gradients, and sPAP. A tricuspid annular plane systolic excursion (TAPSE) ≤17 mm defined RV dysfunction. RV dysfunction was detected in 48 patients (24%). At multivariable regression analysis, LV global longitudinal strain (r = −0.29, P = 0.001), mean aortic gradient (r = 0.25, P = 0.002), and LV ejection fraction (r = 0.18, P = 0.02) were well correlated with TAPSE. After a median 16-month follow-up, cardiovascular death occurred in 17 patients. At multivariate Cox regression analysis, biventricular dysfunction (TAPSE ≤17 mm and LVEF ≤50%) emerged as the strongest predictor of prognosis (hazard ratio 4.08, 95% confidence interval 1.36–12.22; P = 0.012). Conclusions RV dysfunction is common in AS patients, and this finding can likely be accounted for by the RV–LV interdependence. Given that biventricular function impairment was a strong predictor of mortality in our population, we suggest that RV dysfunction should be systematically looked for in AS patients

Introductionsystolic pulmonary artery pressure (sPAP) is a well known predictor of outcome in patients with valvular heart disease. In spite of this fact, limited data are available regarding the assessment of RV function in patients with aortic stenosis (AS).Aimof this study is therefore to evaluate the prevalence and the determinants of RV dysfunction in severe AS patientsMethods201 patients (mean age:79.7±8.7, male sex 55.5%) with severe AS underwent 2D echocardiography and speckle tracking echocardiography (STE) for the evaluation of left ventricular and RV function, aortic valve gradients and sPAP. A tricuspid annular plane systolic excursion (TAPSE) ≤17mm was used to define reduced RV ventricular function.ResultsRV function was impaired in 48 patients (24%). Patients with reduced TAPSE had an impaired LV ejection fraction (LVEF) (49.2±15.4 vs 57.9±10.9%, p

International audience; BACKGROUND: The operative risk of cardiac surgery is ascertained preoperatively on the basis of scores validated in multinational studies. However, the value they add to a simple bedside clinical evaluation (CE) remains controversial. AIMS: To compare operative mortality (defined as death from all causes before the 31st postoperative day) predicted by CE with that predicted by additive and logistic EuroSCOREs, EuroSCORE II and Society of Thoracic Surgeons (STS), Ambler and age-creatinine-ejection fraction (ACEF) scores in patients undergoing aortic valve replacement (AVR) for severe aortic stenosis. METHODS: Overall, 314 consecutive patients were included who underwent AVR between October 2009 and November 2011 (22% with coronary artery bypass graft); mean age 73.4 ± 9.7 years (29% aged\textgreater80 years). Based on CE, patients were divided into four predefined groups of increasing estimated mortality risk: I ≤ 3.9%; II 4-6.9%; III 7-9.9%; IV ≥ 10%. The positive and negative predictive values of the six scores and CE were compared. RESULTS: The observed overall operative mortality was 5.7%. The distribution of the four predicted mortality groups by each score was highly variable. The positive predictive value, calculated for the 64 patients classified at highest risk by CE (groups III or IV) or each score, was 17.2% for EuroSCORE II, 14.1% for CE and STS scores, 10.9% for additive and logistic EuroSCOREs, 10.6% for ACEF and 10.2% for Ambler. The positive predictive value of each score in the low-risk groups (I and II) ranged from 2.8% to 4.4%. CONCLUSION: A simple bedside CE appears as reliable as the various established scores for predicting operative risk in patients undergoing surgical aortic valve replacement. The development and validation of more comprehensive risk stratification tools, including risk factors thus far neglected, seems warranted.

Background Preoperative risk assessment of cardiac surgery is based on international validated scores. However their additional value above simple clinical assessment (CA) remains controversial. The aim of this study was to compare CA by cardiologists with the 5 most commonly used scores (additive and logistic EuroSCORE, EuroSCORE II, STS-score, Ambler-score) to predict perioperative mortality in patients undergoing aortic valve replacement for aortic stenosis. Methods From October 2009 to November 2011, 314 consecutive patients (73±9,7 years; 29% octogenarians) were included. A surgical coronary revascularization was associated to aortic valve replacement in 22%. According to the expected mortality by CA, patients were split in 4 groups: “low” mortality risk [0–3.9%], “intermediate” [4–6.9%], “high” [7–9.9%] and “very high” ≥10%. The 5 scores were calculated for all the patients. Results Observed total operative mortality was 5,7%. The distribution of predicted mortality in the 4 groups was highly different according to the method. The positive predictive value (PPV) of each method was calculated for the 21% most at risk patients (corresponding to the 64 patients ranked in “high” and “very high” mortality risk groups by CA) resulting in PPV=17.2% for EuroSCORE II, 14.1% for CA and STS-score, 10.9% for additive EuroSCORE and logistic EuroSCORE and 10% for Ambler score. Predictive values of “low” and “intermediate” mortality risks were not significantly different depending on the methods (PPV between 2.8 and 4.4%). Conclusion pragmatic CA remains useful to predict operative risk in patients with surgical aortic valve replacement and to balance the different international scores.