Echocardiographic Deformation Imaging for Early Detection of Genetic Cardiomyopathies: JACC Review Topic of the Week

Clinical screening of the relatives of patients with genetic cardiomyopathies is challenging, as they often lack detectable cardiac abnormalities at presentation. Life-threatening adverse events can already occur in these early stages of disease, so sensitive tools to reveal the earliest signs of disease are needed. The utility of echocardiographic deformation imaging for early detection has been explored for this population in multiple studies but has not been broadly implemented in clinical practice. The authors discuss contemporary evidence on the utility of deformation imaging in relatives of patients with genetic cardiomyopathies. The available body of data shows that deformation imaging reveals early disease-specific abnormalities in dilated cardiomyopathy, hypertrophic cardiomyopathy, and arrhythmogenic cardiomyopathy. Deformation imaging seems promising to enhance the screening and follow-up protocols in relatives, and the authors propose measures to accelerate its implementation in clinical care

Некоторые проблемы добычи полезных ископаемых на глубоких горизонтах недр

Cardiovascular screening may benefit middle-aged sportsmen, as coronary artery disease (CAD) is the main cause of exercise-related sudden cardiac death. Arterial stiffness, as measured by pulse wave velocity (PWV), may help identify sportsmen with subclinical CAD. We examined the additional value of PWV measurements to traditional CAD risk factors for identifying CAD.From the Measuring Athlete's Risk of Cardiovascular events (MARC) cohort of asymptomatic, middle-aged sportsmen who underwent low-dose Cardiac CT (CCT) after routine sports medical examination (SME), 193 consecutive sportsmen (aged 55 ± 6.6 years) were included with additional PWV measurements before CCT. Sensitivity, specificity and predictive values of PWV values (>8.3 and >7.5 m/s) assessed by Arteriograph were used to identify CAD (coronary artery calcium scoring ≥ 100 Agatston Units or coronary CT angiography luminal stenosis ≥ 50%) and to assess the additional diagnostic value of PWV to established cardiovascular risk factors.Forty-seven sportsmen (24%) had CAD on CCT. They were older (58.9 vs. 53.8 years, p<0.001), had more hypertension (17 vs. 4%, p=0.003), higher cholesterol levels (5.7 vs. 5.4 mmol/l) p=0.048), and more often were (ever) smokers (55 vs. 34%, p=0.008). Mean PWV was higher in those with CAD (8.9 vs. 8.0 m/s, p=0.017). For PWV >8.3m/s respectively >7.5 m/s sensitivity to detect CAD on CT was 43% and 74%, specificity 69% and 45%, positive predictive value 31% and 30%, and negative predictive value 79% and 84%. Adding PWV to traditional risk factor models did not change the area under the curve (from 0.78 (95% CI = 0.709-0.848)) to AUC 0.78 (95% CI 0.710-0.848, p = 0.99)) for prediction of CAD on CCT.Limited additional value was found for PWV on top of established risk factors to identify CAD. PWV might still have a role to identify CAD in middle-aged sportsmen if risk factors such as cholesterol are unknown

Discovering and Visualizing Disease-Specific Electrocardiogram Features Using Deep Learning: Proof-of-Concept in Phospholamban Gene Mutation Carriers

BACKGROUND: ECG interpretation requires expertise and is mostly based on physician recognition of specific patterns, which may be challenging in rare cardiac diseases. Deep neural networks (DNNs) can discover complex features in ECGs and may facilitate the detection of novel features which possibly play a pathophysiological role in relatively unknown diseases. Using a cohort of PLN (phospholamban) p.Arg14del mutation carriers, we aimed to investigate whether a novel DNN-based approach can identify established ECG features, but moreover, we aimed to expand our knowledge on novel ECG features in these patients. METHODS: A DNN was developed on 12-lead median beat ECGs of 69 patients and 1380 matched controls and independently evaluated on 17 patients and 340 controls. Differentiating features were visualized using Guided Gradient Class Activation Mapping++. Novel ECG features were tested for their diagnostic value by adding them to a logistic regression model including established ECG features. RESULTS: The DNN showed excellent discriminatory performance with a c-statistic of 0.95 (95% CI, 0.91-0.99) and sensitivity and specificity of 0.82 and 0.93, respectively. Visualizations revealed established ECG features (low QRS voltages and T-wave inversions), specified these features (eg, R- and T-wave attenuation in V2/V3) and identified novel PLN-specific ECG features (eg, increased PR-duration). The logistic regression baseline model improved significantly when augmented with the identified features (P<0.001). CONCLUSIONS: A DNN-based feature detection approach was able to discover and visualize disease-specific ECG features in PLN mutation carriers and revealed yet unidentified features. This novel approach may help advance diagnostic capabilities in daily practice

Deep neural network-based clustering of deformation curves reveals novel disease features in PLN pathogenic variant carriers

Echocardiographic deformation curves provide detailed information on myocardial function. Deep neural networks (DNNs) may enable automated detection of disease features in deformation curves, and improve the clinical assessment of these curves. We aimed to investigate whether an explainable DNN-based pipeline can be used to detect and visualize disease features in echocardiographic deformation curves of phospholamban (PLN) p.Arg14del variant carriers. A DNN was trained to discriminate PLN variant carriers (n = 278) from control subjects (n = 621) using raw deformation curves obtained by 2D-speckle tracking in the longitudinal axis. A visualization technique was used to identify the parts of these curves that were used by the DNN for classification. The PLN variant carriers were clustered according to the output of the visualization technique. The DNN showed excellent discriminatory performance (C-statistic 0.93 [95% CI 0.87–0.97]). We identified four clusters with PLN-associated disease features in the deformation curves. Two clusters showed previously described features: apical post-systolic shortening and reduced systolic strain. The two other clusters revealed novel features, both reflecting delayed relaxation. Additionally, a fifth cluster was identified containing variant carriers without disease features in the deformation curves, who were classified as controls by the DNN. This latter cluster had a very benign disease course regarding development of ventricular arrhythmias. Applying an explainable DNN-based pipeline to myocardial deformation curves enables automated detection and visualization of disease features. In PLN variant carriers, we discovered novel disease features which may improve individual risk stratification. Applying this approach to other diseases will further expand our knowledge on disease-specific deformation patterns. Graphical abstract: [Figure not available: see fulltext.] Overview of the deep neural network-based pipeline for feature detection in myocardial deformation curves. Firstly, phospholamban (PLN) p.Arg14del variant carriers and controls were selected and a deep neural network (DNN) was trained to detect the PLN variant carriers. Subsequently, a clustering-based approach was performed on the attention maps of the DNN, which revealed 4 distinct phenotypes of PLN variant carriers with different prognoses. Moreover, a cluster without features and a benign prognosis was detected

Nasopharyngeal Myoepithelial Carcinoma Mimicking Nasopharyngeal Carcinoma

AbstractMyoepithelial carcinoma (malignant myoepithelioma) (MC) is a rare tumor, defined as a malignant salivary neoplasm composed almost exclusively of tumor cells with myoepithelial differentiation. It can arise in unusual location sites, such as the nasopharynx, and may be difficult to approach. Nasopharyngeal MC can sometimes present as a nasopharyngeal mass which may be mistaken for primary nasopharyngeal carcinoma (NPC). The treatment strategy for nasopharyngeal MC is different from NPC, and maximal surgical resection of the main lesion is still considered as the mainstay of therapy. Herein we present a 32-year-old man with a nasopharyngeal mass which was initially mistaken as NPC, and which was later confirmed as MC after a comprehensive review of the pathology

Varespladib and cardiovascular events in patients with an acute coronary syndrome: the VISTA-16 randomized clinical trial

IMPORTANCE: Secretory phospholipase A2(sPLA2) generates bioactive phospholipid products implicated in atherosclerosis. The sPLA2inhibitor varespladib has favorable effects on lipid and inflammatory markers; however, its effect on cardiovascular outcomes is unknown. OBJECTIVE: To determine the effects of sPLA2inhibition with varespladib on cardiovascular outcomes. DESIGN, SETTING, AND PARTICIPANTS: A double-blind, randomized, multicenter trial at 362 academic and community hospitals in Europe, Australia, New Zealand, India, and North America of 5145 patients randomized within 96 hours of presentation of an acute coronary syndrome (ACS) to either varespladib (n = 2572) or placebo (n = 2573) with enrollment between June 1, 2010, and March 7, 2012 (study termination on March 9, 2012). INTERVENTIONS: Participants were randomized to receive varespladib (500 mg) or placebo daily for 16 weeks, in addition to atorvastatin and other established therapies. MAIN OUTCOMES AND MEASURES: The primary efficacy measurewas a composite of cardiovascular mortality, nonfatal myocardial infarction (MI), nonfatal stroke, or unstable angina with evidence of ischemia requiring hospitalization at 16 weeks. Six-month survival status was also evaluated. RESULTS: At a prespecified interim analysis, including 212 primary end point events, the independent data and safety monitoring board recommended termination of the trial for futility and possible harm. The primary end point occurred in 136 patients (6.1%) treated with varespladib compared with 109 patients (5.1%) treated with placebo (hazard ratio [HR], 1.25; 95%CI, 0.97-1.61; log-rank P = .08). Varespladib was associated with a greater risk of MI (78 [3.4%] vs 47 [2.2%]; HR, 1.66; 95%CI, 1.16-2.39; log-rank P = .005). The composite secondary end point of cardiovascular mortality, MI, and stroke was observed in 107 patients (4.6%) in the varespladib group and 79 patients (3.8%) in the placebo group (HR, 1.36; 95% CI, 1.02-1.82; P = .04). CONCLUSIONS AND RELEVANCE: In patients with recent ACS, varespladib did not reduce the risk of recurrent cardiovascular events and significantly increased the risk of MI. The sPLA2inhibition with varespladib may be harmful and is not a useful strategy to reduce adverse cardiovascular outcomes after ACS. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01130246. Copyright 2014 American Medical Association. All rights reserved

Ultrasound enhanced prehospital thrombolysis using microbubbles infusion in patients with acute ST elevation myocardial infarction: Rationale and design of the Sonolysis study

Contains fulltext : 70525.pdf (publisher's version ) (Open Access)ABSTRACT: BACKGROUND -: Experimental studies have shown that ultrasound contrast agents enhance the effectiveness of thrombolytic agents in the presence of ultrasound in vitro and in vivo. Recently, we have launched a clinical pilot study, called "Sonolysis", to study this effect in patients with ST-elevation myocardial infarction based on proximal lesions of the infarct-related artery. METHODS/DESIGN -: In our multicenter, randomized, placebo controlled clinical trial we will include patients between 18 and 80 years of age with their first ST-elevation myocardial infarction based on a proximal lesion of the infarct-related artery. After receiving a single bolus alteplase 50 mg IV (Actilyse(R) Boehringer Ingelheim GmbH), a loading dose of aspirin 500 mg, and heparin 5000 IU in the ambulance according to the prehospital thrombolysis protocol, patients, following oral informed consent, are randomized to undergo 15 minutes of pulsatile ultrasound with intravenous administration of ultrasound contrast agent or placebo without ultrasound. Afterwards coronary angiography and, if indicated, percutaneous coronary intervention will take place. A total of 60 patients will be enrolled in approximately 1 year.The primary endpoints are based on the coronary angiogram and consist of TIMI flow, corrected TIMI frame count, and myocardial blush grade. Follow-up includes 12-lead ECG, 2D-echocardiography, cardiac MRI, and enzyme markers to obtain our secondary endpoints, including the infarct size, wall motion abnormalities, and the global left ventricular function. DISCUSSION -: The Sonolysis study is the first multicenter, randomized, placebo controlled clinical trial investigating the therapeutic application of ultrasound and microbubbles in acute ST-elevation myocardial infarction patients. A positive finding may stimulate further research and technical innovations to implement the treatment in the ambulance and maybe obtain even more patency at an earlier stage. TRIAL REGISTRATION -: Trialregister NTR161