Publications of Patrizio Lancellotti
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See detailA Highly Durable RNAi Therapeutic Inhibitor of PCSK9
LANCELLOTTI, Patrizio ULg; Oury, Cécile ULg

in New England Journal of Medicine (2017), 376

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See detailTargeting of C-type lectin-like receptor 2 or P2Y12 for the prevention of platelet activation by immunotherapeutic CpG oligodeoxynucleotides
Delierneux, Céline ULg; Donis, Nathalie ULg; servais, laurence et al

in Journal of Thrombosis and Haemostasis (2017), 15(5), 983-997

Background: Synthetic phosphorothioate-modified CpG oligodeoxynucleotides (CpG ODNs) display potent immunostimulatory properties that are widely exploited in clinical trials of anticancer treatment ... [more ▼]

Background: Synthetic phosphorothioate-modified CpG oligodeoxynucleotides (CpG ODNs) display potent immunostimulatory properties that are widely exploited in clinical trials of anticancer treatment. Unexpectedly, a recent study indicates that CpG ODNs activate human platelets via the immunoreceptor tyrosine-based activation motif (ITAM)-coupled receptor glycoprotein VI. Objective: To further analyze the mechanisms of CpG ODN-induced platelet activation and identify potential inhibitory strategies. Methods: In vitro analyses were performed on human and mouse platelets, and on cell lines expressing platelet ITAM receptors. CpG ODN platelet activating effects were evaluated in a mouse model of thrombosis. Results: We demonstrated platelet uptake of CpG ODNs, resulting in platelet activation and aggregation. The C-type lectin-like receptor 2 (CLEC-2) expressed in DT40 cells bound CpG ODNs. CpG ODN uptake did not occur in CLEC-2-deficient mouse platelets. Inhibition of human CLEC-2 with a blocking antibody inhibited CpG ODN-induced platelet aggregation. CpG ODNs caused CLEC-2 dimerization, and provoked its internalization. They induced dense granule release before the onset of aggregation. Accordingly, pretreating platelets with apyrase, or inhibiting P2Y12 with cangrelor or clopidogrel prevented CpG ODN platelet activating effect. In vivo, intravenously injected CpG ODN interacted with platelets adhered to mouse injured endothelium, and promoted thrombus growth, which was inhibited by CLEC-2 deficiency or by clopidogrel. Conclusions: CLEC-2 and P2Y12 are required for CpG ODN-induced platelet activation and thrombosis and might be targeted to prevent adverse events in patients at risk. [less ▲]

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See detailPlace du traitement médical bradycardisant dans l’insuffisance cardiaque
tridetti, j; KRZESINSKI, François ULg; D'ORIO, Virginie ULg et al

in Revue Médicale de Liège (2017), 72

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See detailInvited Commentary
Lancellotti, Patrizio ULg; Nchimi Longang, Alain ULg

in Annals of Thoracic Surgery (2017), 103(1), 81-82

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See detailChronic ischemic mitral regurgitation
DULGHERU, Raluca Elena ULg; LANCELLOTTI, Patrizio ULg

in Applied echocardiography in coronary artery disease (2017)

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See detailExercise Testing and Stress Imaging in Mitral Valve Disease.
Voilliot, Damien; Lancellotti, Patrizio ULg

in Current Treatment Options in Cardiovascular Medicine (2017), 19(3), 17

OPINION STATEMENT: Mitral valve disease represented by mitral stenosis and mitral regurgitation is the second most frequent valvulopathy. Mitral stenosis leads to an increased left atrial pressure whereas ... [more ▼]

OPINION STATEMENT: Mitral valve disease represented by mitral stenosis and mitral regurgitation is the second most frequent valvulopathy. Mitral stenosis leads to an increased left atrial pressure whereas mitral regurgitation leads to an increased left atrial pressure associated with a volume overload. Secondary to an upstream transmission of this overpressure, both mitral stenosis and regurgitation lead to pulmonary hypertension and right heart failure. In addition, mitral regurgitation also leads to left ventricular dilatation and dysfunction with left heart failure. Depending on the anatomy of the valvular and subvalvular apparatus, valve repair (percutaneous mitral commissurotomy for mitral stenosis and valvuloplasty for mitral regurgitation) might be possible. If the anatomy is not favorable, valve replacement by mechanical or biological prosthesis is indicated. Most of the intervention indications are based on clinical symptoms and resting transthoracic echocardiography. Outcomes of patients operated based upon resting echo abnormalities might however not be optimal. Therefore early intervention might be beneficial based upon abnormal exercise testing, which has been demonstrated to more sensitive to identify high-risk patients. In this last decade, especially exercise echocardiography has been found to be a crucial tool in the management of patients with mitral valve disease. [less ▲]

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See detailMaladie coronaire et pratique sportive
ANCION, Arnaud ULg; KAUX, Jean-François ULg; PIERARD, Luc ULg et al

in Revue Médicale de Liège (2017), 72(6), 281-287

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See detailAortic root calcium burden and post-transcatheter aortic valve implantation paravulvar leak : Can't Live Without It, Can't Live With It.
Qian, Z; Lancellotti, Patrizio ULg; Vannan, MA

in European Heart Journal - Cardiovascular Imaging (2017)

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See detailLe medicament du mois BIPRESSIL(R) : Premiere association fixe bisoprolol et perindopril arginine.
GACH, Olivier ULg; FALQUE, Bertrand ULg; CANIVET, Antoine ULg et al

in Revue Médicale de Liège (2017), 72(5), 260-265

In patients suffering from systemic arterial hypertension, coronary artery disease, or heart failure, beta-blockers and angiotensin-convertase enzyme inhibitors play a major therapeutic and preventive ... [more ▼]

In patients suffering from systemic arterial hypertension, coronary artery disease, or heart failure, beta-blockers and angiotensin-convertase enzyme inhibitors play a major therapeutic and preventive role. Coronary artery disease remains the leading cause of mortality in industrialized countries. Unless adapted preventive strategy, notably pharmacological interventions, cardiovascular events in these patients remain high. One reason for this relative failure is represented by non-adherence to treatment. A treatment consisting in an association in one pill of several different molecules should confer a higher treatment compliance and thus efficacy. This article describes the characteristics of the first available dual association between a cardioselective beta-blocker agent, bisoprolol, and an angiotensin-convertase enzyme inhibitor, perindopril arginine. [less ▲]

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See detailSerum albumin level and hospital mortality in acute non-ischemic heart failure.
ANCION, Arnaud ULg; Allepaerts, Sophie; Oury, Cécile ULg et al

in ESC heart failure (2017), 4(2), 138-145

AIMS: Hypoalbuminemia is common in heart failure (HF), especially in elderly patients. It is associated with an increased risk of death. The present study sought to examine the prognostic significance of ... [more ▼]

AIMS: Hypoalbuminemia is common in heart failure (HF), especially in elderly patients. It is associated with an increased risk of death. The present study sought to examine the prognostic significance of serum albumin level in the prediction of hospital mortality in patients admitted for acute non-ischemic HF. METHODS AND RESULTS: We examined the association between albumin and hospital mortality in a cohort of 546 patients admitted for acute non-ischemic HF. None of the patients had infectious disease, severe arrhythmias (atrial fibrillation, ventricular tachycardia, ventricular fibrillation), required invasive ventilation, or presented with acute coronary syndrome or primary valvular disease. Thirty-six patients (7%) died during the hospital stay. These patients were significantly older (78 +/- 9 vs. 72 +/- 12 years; P = 0.006), had higher heart rate (P < 0.0001), increased creatinine level (P = 0.01), lower systolic and diastolic blood pressures (P < 0.05), elevated leucocyte count (P = 0.001), and lower albumin levels (31.3 +/- 5.6 g/L vs. 36.9 +/- 4.1 g/L; P < 0.001). With multivariable analysis, age (P = 0.01), heart rate (P < 0.0003), diastolic blood pressure (P < 0.01), leukocyte count (P = 0.009), and serum albumin level (P < 0.0001) emerged as independent predictors of hospital mortality. Hypoalbuminemia (<34 g/L) yielded the best sensitivity (78.8%) and specificity (75%) for predicting hospital death. CONCLUSIONS: Serum albumin level measured at admission can serve as a simple prognostic factor in acute non-ischemic HF. Hypoalbuminemia is associated with increased risk of hospital mortality, especially in elderly patients. [less ▲]

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See detailFibrillation auriculaire et anticoagulation chez le patient hémodialysé : une décision difficile
DELANAYE, Pierre ULg; BOUQUEGNEAU, Antoine ULg; DUBOIS, Bernard ULg et al

in Néphrologie & Thérapeutique (2017)

Cardiovascular mortality of hemodialysis patients remains a major problem. The prevalence and incidence of atrial fibrillation in this population are more important than in the general population. The ... [more ▼]

Cardiovascular mortality of hemodialysis patients remains a major problem. The prevalence and incidence of atrial fibrillation in this population are more important than in the general population. The indication of antivitamin K therapy (AVK) in this context of atrial fibrillation must be weighted against the increased risk of bleeding. Unfortunately, and contrary to the general population, an indication of anticoagulation based on embolic or hemorrhagic risk scores is not as clearly established in the hemodialysis population. No prospective randomized study has investigated the benefit/risk balance of anticoagulant treatment in hemodialysis subjects. This article is a review of the current literature on this topic, showing the prevalence of thromboembolic but also bleeding events in the hemodialysis population. The impact of AVK treatment in this specific population is also reviewed. To the best of our knowledge, the indication of treatment must be individualized. [less ▲]

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See detailMid-term results of bicuspid aortic valve repair guided by morphology and function assessment.
Fattouch, K; Moscarelli, M; Castrovinci, S et al

in Interactive Cardiovascular and Thoracic Surgery (2017)

OBJECTIVES: Bicuspid aortic valve (BAV) is frequently associated with aortic insufficiency (AI) due to cusp disease and/or aortic root dilatation. Based on functional classification and morphology, a ... [more ▼]

OBJECTIVES: Bicuspid aortic valve (BAV) is frequently associated with aortic insufficiency (AI) due to cusp disease and/or aortic root dilatation. Based on functional classification and morphology, a systematic surgical approach was used for aortic valve repair (AVr). METHODS: : From 2004 to 2014, 152 consecutive patients (mean age 55 ± 7 years) with BAV underwent AVr with or without concomitant aortic root surgery. Cusp pathology was treated with central plication in 60 (39.5%) patients, free edge reinforcement in 45 (29.6%), triangular resection in 28 (18.4%) and pericardial patch in 19 (12.5%). Aortic root dilatation was corrected with valve sparing reimplantation in 65 patients. Mean follow-up was 68 ± 36 months. RESULTS: : In-hospital death was 1.3%. Overall 5-year survival was 88.6 ± 3.6%. Freedom from recurrent ≥ grade 2 AI requiring reoperation at 5-year was 93 ± 3.1%. Five-year freedom from reintervention was 98.4 ± 1.6%, 93.3 ± 6.4% and 82.6 ± 9.6 in the group of patients treated with AVr and reimplantation technique, AVr and subcommissural plasty and AVr repair alone (log-rank P  = 0.005). Commissural orientation <160°, type 2 Siever's BAV and preoperative annulus diameter >29 mm were identified as predictors for recurrent ≥ grade 2 AI. CONCLUSIONS: : BAV repair could be achieved with low incidence of recurrent AI, especially when concomitant annulus stabilization was performed. Systematic preoperative morphological and functional characteristics of the aortic valve should be carried out in order to reduce the risk of repair failure. [less ▲]

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See detailRecommendations on the Echocardiographic Assessment of Aortic Valve Stenosis: A Focused Update from the European Association of Cardiovascular Imaging and the American Society of Echocardiography
Baumgartner, H; Hung, J; Bermejo, J et al

in Journal of the American Society of Echocardiography (2017)

Echocardiography is the key tool for the diagnosis and evaluation of aortic stenosis. Because clinical decision-making is based on the echocardiographic assessment of its severity, it is essential that ... [more ▼]

Echocardiography is the key tool for the diagnosis and evaluation of aortic stenosis. Because clinical decision-making is based on the echocardiographic assessment of its severity, it is essential that standards are adopted to maintain accuracy and consistency across echocardiographic laboratories. Detailed recommendations for the echocardiographic assessment of valve stenosis were published by the European Association of Echocardiography and the American Society of Echocardiography in 2009. In the meantime, numerous new studies on aortic stenosis have been published with particular new insights into the difficult subgroup of low gradient aortic stenosis making an update of recommendations necessary. The document focuses in particular on the optimization of left ventricular outflow tract assessment, low flow, low gradient aortic stenosis with preserved ejection fraction, a new classification of aortic stenosis by gradient, flow and ejection fraction, and a grading algorithm for an integrated and stepwise approach of aortic stenosis assessment in clinical practice. [less ▲]

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See detailThree-Dimensional Morphology of the Left Ventricular Outflow Tract: Impact on Grading Aortic Stenosis Severity.
Caballero, Luis; Saura, Daniel; Oliva-Sandoval, Maria Jose et al

in Journal of the American Society of Echocardiography : official publication of the American Society of Echocardiography (2017), 30(1), 28-35

BACKGROUND: Left ventricular outflow tract (LVOT) measurement is a critical step in the quantification of aortic valve area. The assumption of a circular morphology of the LVOT may induce some errors. The ... [more ▼]

BACKGROUND: Left ventricular outflow tract (LVOT) measurement is a critical step in the quantification of aortic valve area. The assumption of a circular morphology of the LVOT may induce some errors. The aim of this study was to assess the three-dimensional (3D) morphology of the LVOT and its impact on grading aortic stenosis severity. METHODS: Fifty-eight patients with aortic stenosis were studied retrospectively. LVOT dimensions were measured using 3D transesophageal echocardiography at three levels: at the hinge points (HP) of the aortic valve and at 4 and 8 mm proximal to the annular plane. Results were compared with standard two-dimensional echocardiographic measurements. RESULTS: Three-dimensional transesophageal echocardiography showed a funnel shape that was more circular at the HP and more elliptical at 4 and 8 mm proximal to the annular plane (circularity index = 0.92 vs 0.83 vs 0.76, P < .001). Cross-sectional area was smaller at the HP and larger at 4 and 8 mm from the annular plane (3.6 vs 3.9 vs 4.1 cm2, P = .001). The best correlation between two-dimensional and 3D transesophageal echocardiographic dimensions was at the HP (intraclass correlation coefficient = 0.75; 95% CI, 0.59-0.86). When the HP approach was selected, there was a reduction in the percentage of patients with low flow (from 41% to 29%). CONCLUSIONS: A large portion of patients with aortic stenosis have funnel-shaped and elliptical LVOTs, a morphology that is more pronounced in the region farther from the annular plane. Two-dimensional LVOT measurement closer to the annular plane has the best correlation with 3D measurements. Measurement of the LVOT closer to the annular plane should be encouraged to reduce measurement errors. [less ▲]

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See detailCardiopulmonary exercise testing is a better outcome predictor than exercise echocardiography in asymptomatic aortic stenosis.
Domanski, Olivia; Richardson, Marjorie; Coisne, Augustin et al

in International Journal of Cardiology (2017), 227

BACKGROUND: Objective assessment of maximal aerobic capacity using peak oxygen consumption (peak VO2) can be helpful in the management of patients with asymptomatic aortic stenosis (AS). The relationship ... [more ▼]

BACKGROUND: Objective assessment of maximal aerobic capacity using peak oxygen consumption (peak VO2) can be helpful in the management of patients with asymptomatic aortic stenosis (AS). The relationship between peak VO2 and AS severity criteria derived from rest and supine exercise echocardiography (SEE) has never been explored. OBJECTIVES: We aimed to determine whether low peak VO2 (<85% of predicted value) is associated with severity parameters in SEE, and poor clinical outcome. METHODS: Fifty one asymptomatic patients (mean age of 54+/-21years) with moderate to severe aortic stenosis (Vmax>3m/s) and left ventricle ejection fraction>50% prospectively underwent resting and SEE and cardiopulmonary exercise testing (CPX). RESULTS: Peak VO2 was lower than expected (21.9+/-7.4mL/kg/min), i.e. <85% of predicted value in 57% patients, secondary to cardiac limitation in most of them (69%). In multiple regression analysis, age, BMI and female gender were the only independent determinants of peak VO2. Interestingly no parameter derived from SEE was associated with peak VO2. After 21+/-7month follow-up, no patient died, 20 underwent cardiac surgery. Peak VO2<85% of predicted value was associated with lower event free survival compared to normal peak VO2 (57%+/-11% vs 93+/-6%, p=0.036) whereas no exercise echocardiographic parameter could predict such events. Peak VO2>/=85% had a negative predictive value of 97%. CONCLUSION: CPX detects a high proportion of false asymptomatic AS patients with poorer outcome that cannot be predicted by SEE markers of AS severity. Assessment of aerobic capacity should be part of current approach within a "watchful waiting" strategy. [less ▲]

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See detailComprehensive multi-modality imaging approach in arrhythmogenic cardiomyoapthy : an expert consensus document of the European Association of Cardiovascular Imaging
Haugaa, KH; Basso, C; Badano, LP et al

in European Heart Journal - Cardiovascular Imaging (2017)

Arrhythmogenic cardiomyopathy (AC) is a progressive disease with high risk of life-threatening ventricular arrhythmias. A genetic mutation is found in up to 50-60% of probands, mostly affecting desmosomal ... [more ▼]

Arrhythmogenic cardiomyopathy (AC) is a progressive disease with high risk of life-threatening ventricular arrhythmias. A genetic mutation is found in up to 50-60% of probands, mostly affecting desmosomal genes. Diagnosis of AC is made by a combination of data from different modalities including imaging, electrocardiogram, Holter monitoring, family history, genetic testing, and tissue properties. Being a progressive cardiomyopathy, repeated cardiac imaging is needed in AC patients. Repeated imaging is important also for risk assessment of ventricular arrhythmias. This expert consensus document gives clinical recommendations for how to use multi-modality imaging in the different aspects of AC disease, including diagnosis, family screening, follow-up, risk assessment, and differential diagnosis. [less ▲]

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See detailRecommendations on the echocardiographic assessment of aortic valve stenosis: a focused update from the European Association of Cardiovascular Imaging and the American Society of Echocardiography
Baumgartner, HC; Hung, J Co-Chair; Bermejo, J et al

in European Heart Journal - Cardiovascular Imaging (2017)

Echocardiography is the key tool for the diagnosis and evaluation of aortic stenosis. Because clinical decision-making is based on the echocardiographic assessment of its severity, it is essential that ... [more ▼]

Echocardiography is the key tool for the diagnosis and evaluation of aortic stenosis. Because clinical decision-making is based on the echocardiographic assessment of its severity, it is essential that standards are adopted to maintain accuracy and consistency across echocardiographic laboratories. Detailed recommendations for the echocardiographic assessment of valve stenosis were published by the European Association of Echocardiography and the American Society of Echocardiography in 2009. In the meantime, numerous new studies on aortic stenosis have been published with particular new insights into the difficult subgroup of low gradient aortic stenosis making an update of recommendations necessary. The document focuses in particular on the optimization of left ventricular outflow tract assessment, low flow, low gradient aortic stenosis with preserved ejection fraction, a new classification of aortic stenosis by gradient, flow and ejection fraction, and a grading algorithm for an integrated and stepwise approach of artic stenosis assessment in clinical practice. [less ▲]

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