Julien Ternacle

Clinical Implications of Echocardiographic Phenotypes of Patients With Diabetes Mellitus

BACKGROUNDnType 2 diabetes mellitus (T2DM) may alter cardiac structure and function, but obesity, hypertension (HTN), or aging can induce similar abnormalities.nnnOBJECTIVESnThis study sought to link cardiac phenotypes in T2DM patients with clinical profiles and outcomes using cluster analysis.nnnMETHODSnBaseline echocardiography and a composite endpoint (cardiovascular mortality and hospitalization) were evaluated in 842 T2DM patients from 2 prospective cohorts. A cluster analysis was performed on echocardiographic variables, and the association between clusters and clinical profiles and outcomes was assessed.nnnRESULTSnThree clusters were identified. Cluster 1 patients had the lowest left ventricular (LV) mass index and ratio between early mitral inflow velocity and mitral annular early diastolic velocity (E/e) ratio, had the highest left ventricular ejection fraction (LVEF), and were predominantly male with the lowest rate of obesity or HTN. Cluster 2 patients had thexa0highest strain and highest E/e ratio, were the oldest, were predominantly female, and had the lowest rate of isolated T2DM (without HTN or obesity). Cluster 3 patients had the highest LV mass index and volumes and the lowest LVEF andxa0strain, were predominantly male, and shared similar age and rate of obesity and HTN as cluster 1 patients. Afterxa0follow-up of 67xa0months (interquartile range: 40 to 87), the composite endpoint occurred in 56 of 521 patients (10.8%). Clusters 2 (hazard ratio: 2.37; 95% confidence interval: 1.15 to 4.88) and 3 (hazard ratio: 2.19; 95% confidence interval: 1.00 to 4.82) had a similar outcome, which was worse than clusterxa01.nnnCONCLUSIONSnCluster analysis of echocardiographic variables identified 3 different echocardiographic phenotypes of T2DM patients that were associated with distinct clinical profiles and highlighted the prognostic value of LVxa0remodeling and subclinical dysfunction.

Visceral Adipose Tissue Drives Cardiac Aging Through Modulation of Fibroblast Senescence by Osteopontin Production

Background: Aging induces cardiac structural and functional changes linked to the increased deposition of extracellular matrix proteins, including OPN (osteopontin), conducing to progressive interstitial fibrosis. Although OPN is involved in various pathological conditions, its role in myocardial aging remains unknown. Methods: OPN deficient mice (OPN-/-) with their wild-type (WT) littermates were evaluated at 2 and 14 months of age in terms of cardiac structure, function, histology and key molecular markers. OPN expression was determined by reverse-transcription polymerase chain reaction, immunoblot and immunofluorescence. Luminex assays were performed to screen plasma samples for various cytokines/adipokines in addition to OPN. Similar explorations were conducted in aged WT mice after surgical removal of visceral adipose tissue (VAT) or treatment with a small-molecule OPN inhibitor agelastatin A. Primary WT fibroblasts were incubated with plasma from aged WT and OPN-/- mice, and evaluated for senescence (senescence-associated &bgr;-galactosidase and p16), as well as fibroblast activation markers (Acta2 and Fn1). Results: Plasma OPN levels increased in WT mice during aging, with VAT showing the strongest OPN induction contrasting with myocardium that did not express OPN. VAT removal in aged WT mice restored cardiac function and decreased myocardial fibrosis in addition to a substantial reduction of circulating OPN and transforming growth factor &bgr; levels. OPN deficiency provided a comparable protection against age-related cardiac fibrosis and dysfunction. Intriguingly, a strong induction of senescence in cardiac fibroblasts was observed in both VAT removal and OPN-/- mice. The addition of plasma from aged OPN-/- mice to cultures of primary cardiac fibroblasts induced senescence and reduced their activation (compared to aged WT plasma). Finally, Agelastatin A treatment of aged WT mice fully reversed age-related myocardial fibrosis and dysfunction. Conclusions: During aging, VAT represents the main source of OPN and alters heart structure and function via its profibrotic secretome. As a proof-of-concept, interventions targeting OPN, such as VAT removal and OPN deficiency, rescued the heart and induced a selective modulation of fibroblast senescence. Our work uncovers OPN’s role in the context of myocardial aging and proposes OPN as a potential new therapeutic target for a healthy cardiac aging.

Diuretic versus placebo in normotensive acute pulmonary embolism with right ventricular enlargement and injury: a double-blind randomised placebo controlled study. Protocol of the DiPER study

Introduction In acute pulmonary embolism (PE), poor outcome is usually related to right ventricular (RV) failure due to the increase in RV afterload. Treatment of PE with RV failure without shock is controversial and usually relies on fluid expansion to increase RV preload. However, several studies suggest that fluid expansion may worsen acute RV failure by increasing RV dilation and ischaemia, and increase left ventricular compression by RV dilation. By reducing RV enlargement, diuretic treatment may break this vicious circle and provide early improvement in normotensive patients referred for acute PE with RV failure. Methods and analysis The Diuretic versus placebo in Pulmonary Embolism with Right ventricular enlargement trial (DiPER) is a prospective, multicentre, randomised (1:1), double-blind, placebo controlled study assessing the superiority of furosemide as compared with placebo in normotensive patients with confirmed acute PE and RV dilation (diagnosed on echocardiography or CT of the chest) and positive brain natriuretic peptide result. The primary end point will be a combined clinical criterion derived from simplified Pulmonary Embolism Severity Index (PESI) score and evaluated at 24u2005h. It will include: (1) urine output >0.5u2005mL/kg/min for the past 24u2005h; (2) heart rate <110u2005bpm; (3) systolic blood pressure >100u2005mmu2005Hg and (4) arterial oxyhaemoglobin level >90%. Thirty-day major cardiac events defined as death, cardiac arrest, mechanical ventilation, need for catecholamine and thrombolysis, will be evaluated as a secondary end point. Assuming an increase of 30% in the primary end point with furosemide and a β risk of 10%, 270 patients will be required. Ethics and dissemination Ethical approval was received from the ethical committee of Ile de France (2014-001090-14). The findings of the trial will be disseminated through peer-reviewed journals, and national and international conference presentations. Trial registration number NCT02268903.

Short-term high-fat diet compromises myocardial function: a radial strain rate imaging study.

AimnLong-term high-fat diet (HFD) induces both cardiac remodelling and myocardial dysfunction in murine models. The aim was to assess the time course and mechanisms of metabolic and cardiac modifications induced by short-term HFD in wild-type (WT) mice.nnnMethods and resultsnThirty-three WT mice were subjected to HFD (60% fat, nu2009=u200916) and chow diet (CD, 13% fat, nu2009=u200917). Metabolic and echocardiographic data were collected at baseline and every 5 weeks for 20 weeks. Invasive haemodynamic data and myocardial samples were collected at 5 and 20 weeks. Echocardiographic data included left ventricular (LV) diameters and thickness, and systolic function using radial strain rate (SR). Histological assessment of cardiomyocyte and adipocyte sizes, interstitial fibrosis, and apoptosis index were performed. During follow-up, body weight, and glycaemia levels were higher in HFD than in CD mice, in association with an early adipose tissue remodelling. Despite no difference between both groups in blood pressure and LV mass at 5 weeks, an early LV dysfunction was observed in HFD mice as assessed by radial SR (21u2009±u20090.8 vs. 27u2009±u20090.8 unit/s, Pu2009<u20090.001) and haemodynamic assessment. During follow-up, both groups demonstrated a progressive systolic and diastolic LV dysfunction and remodelling including dilatation and hypertrophy, which were more severe in HFD mice. Compared with CD mice, the early LV impairment in HFD mice was coupled with a higher cardiomyocyte apoptosis level (0.95 vs. 0.02%, Pu2009<u20090.05) associated with an interstitial fibrosis process (2.3 vs. 0.2%, Pu2009<u20090.05), which worsen during follow-up.nnnConclusionnThe HFD promoted early metabolic and cardiac dysfunctions, and adipose and myocardial tissues remodelling.

Left Atrial Appendage Occluder Thrombosis After Successful Implantation

We report the case of a 69-year-old woman admitted for recurrent left atrial appendage (LAA) thrombosis occurring 8 months after implantation of an Amplatzer Cardiac Plug device.nnThe indication for LAA closure was paroxysmal atrial fibrillation with high thromboembolic risk (CHA2DS2-Vasc score, 4) and a history of intracranial bleeding 6 months previously under vitamin K antagonist with an international normalized ratio ranging from 2 to 3. The Amplatzer Cardiac Plug …

A New Three-Dimensional Echocardiography Method to Quantify Aortic Valve Calcification

Background: Aortic valve calcification (AVC) quantification is computed from multidetector computed tomography (MDCT). The aim of this study was to test the hypothesis that three‐dimensional (3D) transthoracic echocardiography can be used to provide a bedside method to assess AVC. Methods: The study included 94 patients (mean age, 78 ± 12 years; mean aortic valve [AV] area, 1.0 ± 0.6 cm2) referred for MDCT and echocardiography for AV assessment. Apical 3D full‐volume data sets focused on the AV region were acquired during transthoracic echocardiography, and a region‐growing algorithm was applied offline to compute 3D transthoracic echocardiographic AVC (AVC‐3DEcho). AVC‐3DEcho was compared with AVC by MDCT and with calcium weight in the subgroup of patients referred for surgery, with explanted AVs analyzed by a pathologist (n = 22). Results: In the explanted valve group, AVC‐3DEcho score exhibited fair correlations with MDCT score (r = 0.85, P < .001), calcium load (r = 0.81, P < .001), and peak AV velocity (r = 0.64, P < .001). In the overall population, AVC‐3DEcho score correlated modestly with MDCT score (r = 0.61, P < .001) but had similar accuracy to identify severe aortic stenosis (area under the curve = 0.94). AVC‐3DEcho > 1,054 mm3 identified severe aortic stenosis with specificity of 100% and sensitivity of 76%. In addition, AVC‐3DEcho was associated with the presence of significant paravalvular regurgitation after transcatheter aortic valve implantation. Finally, intraobserver and interobserver variability for AVC‐3DEcho score was 4.2% and 8.9%, respectively. Conclusions: AVC‐3DEcho correlated with calcium weight obtained from pathologic analysis and MDCT. These data suggest that a bedside method for quantifying AV calcification with ultrasound is feasible. Highlights:A method to quantify AVC by 3D TTE is proposed and evaluated in patients with AS.The AVC‐3DEcho score correlated with calcium weight, MDCT score, and AS severity.AVC by 3D echocardiography was associated with paravalvular leak after TAVI.

Intra-coronary morphine versus placebo in the treatment of acute ST-segment elevation myocardial infarction: the MIAMI randomized controlled trial

BackgroundExperimental studies suggest that morphine may protect the myocardium against ischemia-reperfusion injury by activating salvage kinase pathways. The objective of this two-center, randomized, double-blind, controlled trial was to assess potential cardioprotective effects of intra-coronary morphine in patients with ST-segment elevation myocardial infarction (STEMI) referred for primary percutaneous intervention.MethodsNinety-one patients with STEMI were randomly assigned to intracoronary morphine (1xa0mg) or placebo at reperfusion of the culprit coronary artery. The primary endpoint was infarct size/left ventricular mass ratio assessed by magnetic resonance imaging on day 3–5. Secondary endpoints included the areas under the curve (AUC) for troponin T and creatine kinase over three days, left ventricular ejection fraction assessed by echocardiography on days 1 and 6, and clinical outcomes.ResultsInfarct size/left ventricular mass ratio was not significantly reduced by intracoronary morphine compared to placebo (27.2%u2009±u200915.0% vs. 30.5%u2009±u200910.6%, respectively, pu2009=u20090.28). Troponin T and creatine kinase AUCs were similar in the two groups. Morphine did not improve left ventricular ejection fraction on day 1 (49.7u2009±u200910.3% vs. 49.3u2009±u20099.3% with placebo, pu2009=u20090.84) or day 6 (48.5u2009±u200910.2% vs. 49.0u2009±u20098.5% with placebo, pu2009=u20090.86). The number of major adverse cardiac events, including stent thrombosis, during the one-year follow-up was similar in the two groups.ConclusionsIntracoronary morphine at reperfusion did not significantly reduce infarct size or improve left ventricular systolic function in patients with STEMI. Presence of comorbidities in some patients may contribute to explain these results.Trial registrationClinicalTrials.gov, NCT01186445 (date of registration: August 23, 2010).

Does peri-device leak after left atrial appendage closure impact patient outcome?

Background Limited studies reported the rate and clinical impact of peri-device leaks (PDL) after percutaneous left atrial appendage closure (LAAC). Method All consecutive patients admitted for LAAC between November 2011 and October 2016 (nxa0=xa083) were prospectively enrolled. LAAC was performed under sedation using fluoroscopy and trans-esophageal echocardiography (TEE) monitoring. The follow-up included clinical, TEE and/or cardiac computed tomography angiography (CCTA). PDL was defined by the presence of contrast within the LAA on CCTA, and MACE included stroke, device-related thrombosis and cardiovascular death. LAAC failures (nxa0=xa03) and patients without imaging during follow-up were excluded (nxa0=xa010). Results Overall, 70 patients (mean age 75xa0±xa08 years, mean CHA2DS2-VAScxa0=xa04.4xa0±xa01.5 and mean HAS-BLED 3.4xa0±xa01.1) were implanted using Amplatzer Cardiac Plug (nxa0=xa024), Amulet (nxa0=xa032) or Watchman devices (nxa0=xa014). Indications were stroke recurrence under optimal treatment (nxa0=xa07) or contraindication to anticoagulation (nxa0=xa063). After LAAC, patients with a contraindication to anticoagulation received antiplatelet therapy alone (aspirin alone, nxa0=xa033). On CCTA at 3, 6 and 12 months, PDL was observed respectively in 70% (46/66), 64% (27/42) and 50% (13/26) of patients. Patients with PDL had a larger LAA diameter (21xa0±xa03xa0mm vs. 18xa0±xa03xa0mm, Pxa0=xa00.01) and a lower prosthesis compression (13xa0±xa07% vs. 9xa0±xa07%, Pxa0=xa00.02). During follow-up (median 261xa0days [147–399]), MACE were observed in 7.1% of patients including 2 strokes, 2 device-related thrombosis, and 1 cardiovascular death. The presence of a PDL was not associated with MACE. Conclusion PDL is frequently observed (>xa050%) after LAAC and tends to decrease over the time. No association is observed between PDL and MACE.

Usefulness of echocardiographic-fluoroscopic fusion imaging in adult structural heart disease

Percutaneous approaches to treat structural heart diseases are growing in number and complexity. Multimodality imaging is essential for planning and monitoring such interventions. The combination of three-dimensional transoesophageal echocardiography with fluoroscopy is the cornerstone of interventional imaging. However, these two modalities are displayed on separate screens, and are handled by different physicians, which requires a complex mental reconstruction for the interventional team. To overcome this issue, echocardiographic-fluoroscopic fusion imaging has been introduced recently in clinical practice. This system combines, in a single view, the precise visualization of catheter and devices provided by fluoroscopy with the continuous soft tissue information provided by echocardiography. In addition, the procedure may be guided using a marker-tracking mode. However, there are few data on how this new technology can have an impact on our routine clinical practice and patient outcomes. In this review, we provide a user manual for the system, discuss its potential clinical applications in adult structural heart diseases and consider future perspectives.

Transoesophageal echocardiography current practice in France: A multicentre study

BACKGROUNDnFew data are available on the application of transoesophageal echocardiography (TOE) recommendations in daily practice.nnnAIMSnTo evaluate TOE practice based on echocardiography societies guidelines, and to determine complication rates and factors associated with patient feelings.nnnMETHODSnBetween April and June 2017, we prospectively included all consecutive patients referred to 14 French hospitals for a transoesophageal echocardiogram (TOE). A survey was taken just after the examination, which included questions about pre-procedural anxiety, and any pain, unpleasant feeling or breathing difficulties experienced during the examination.nnnRESULTSnOverall, 1718 TOEs were performed, mainly for stroke evaluation. A standardized operating procedure checklist was completed in half of the patients before the examination. TOE was unpleasant for 62.4% of patients, but was stopped for agitation or intolerance in 3.5 and 1.4% of cases, respectively. We observed one severe complication (pulmonary oedema). The mean TOE duration was short (9.2±4.6minutes), but was longer with residents than with more experienced physicians (11±4.7 vs. 8.8±4.7minutes for junior physicians [P=0.0027]; vs. 8.9±4.8minutes for senior physicians [P=0.0013]; and vs. 7.5±4.1minutes for associate professors/professors [P<0.0001]). The visual analogue scale (VAS) score after TOE was good (8.3±1.7 out of 10), and was better in patients with general anaesthesia (GA) than in those without GA (9.3±0.9 vs. 8.1±1.7; P<0.0001). In patients without GA, the VAS score was similar with and without local anaesthesia (8.1±1.7 vs. 8.2±1.6; P=0.19). After multivariable adjustment, absence of anxiety before TOE and greater operator experience were consistently associated with a higher VAS score.nnnCONCLUSIONSnTOE is safe, with a low rate of complications and few stops for intolerance. A shorter TOE duration and better patient feelings were observed for experienced operators, highlighting the importance of the learning curve, and paving the way for teaching on a TOE simulator.