Left Atrial Glucose Metabolism Evaluation by 18F-FDG-PET in Persistent Atrial Fibrillation and in Sinus Rhythm.

The role of atrial metabolism alterations for initiation and atrial fibrillation (AF) persistence remains poorly understood. Therefore, we evaluated left atrial glucose metabolism by nicotinic acid derivative stimulated 18-fluorodeoxyglucose positron emission tomography in 36 patients with persistent AF undergoing catheter ablation before and 3 months after return to sinus rhythm and compared values against healthy controls. Under identical hemodynamics and metabolic conditions, and although left ventricular FDG uptake remained unchanged, patients in persistent AF presented significantly higher total left atrial and left atrial appendage uptake, which decreased significantly after return to sinus rhythm, despite improvement of passive and active atrial contractile function. These findings support a role of altered glucose metabolism and metabolic wasting underlying the pathophysiology of persistent AF.

Evaluation and management of patients with coronary chronic total occlusions considered for revascularisation. A clinical consensus statement of the European Association of Percutaneous Cardiovascular Interventions (EAPCI) of the ESC, the European Association of Cardiovascular Imaging (EACVI) of the ESC, and the ESC Working Group on Cardiovascular Surgery.

Chronic total occlusions (CTOs) of coronary arteries can be found in the context of chronic or acute coronary syndromes; sometimes they are an incidental finding in those apparently healthy individuals undergoing imaging for preoperative risk assessment. Recently, the invasive management of CTOs has made impressive progress due to sophisticated preinterventional assessment, including advanced non-invasive imaging, the availability of novel and dedicated tools for CTO percutaneous coronary intervention (PCI), and experienced interventionalists working in specialised centres. Thus, it is crucial that referring physicians who see patients with CTO be aware of recent developments and of the initial evaluation requirements for such patients. Besides a careful history and clinical examination, electrocardiograms, exercise tests, and non-invasive imaging modalities are important for selecting the patients most suitable for CTO PCI, while others may be referred to coronary artery bypass graft or optimal medical therapy only. While CTO PCI improves angina and reduces the use of antianginal drugs in patients with symptoms and proven ischaemia, hibernation and/or wall motion abnormalities at baseline or during stress, the effect of CTO PCI on major cardiovascular events is still controversial. This clinical consensus statement specifically focuses on referring physicians, providing a comprehensive algorithm for the preinterventional evaluation of patients with CTO and the current evidence for the clinical effectiveness of the procedure. The proposed care track has been developed by members and with the support of the European Association of Percutaneous Cardiovascular Interventions (EAPCI), the European Association of Cardiovascular Imaging (EACVI), and the European Society of Cardiology (ESC) Working Group on Cardiovascular Surgery.

Carbohydrate antigen 125: a useful marker of congestion, fibrosis, and prognosis in heart failure with preserved ejection fraction.

AIMS: Heart failure (HF) with preserved ejection fraction (HFpEF) is a disease associated with high morbidity and mortality, for which it is difficult to identify patients with the poorest prognosis in routine clinical practice. Carbohydrate antigen 125 (CA 125) has been shown to be a potential marker of congestion and prognosis in HF. We sought to better characterize HFpEF patients with high CA 125 levels by using a multimodal approach. METHODS AND RESULTS: We prospectively enrolled 139 HFpEF patients (78 ± 8 years; 60% females) and 25 controls matched for age and sex (77 ± 5 years; 60% females). They underwent two-dimensional echocardiography, cardiac magnetic resonance with late gadolinium enhancement [including extracellular volume (ECV) measurement], and serum measurements of CA 125 level. The primary endpoint of the study was a composite of all-cause mortality or first HF hospitalization. The prognostic impact of CA 125 was determined using Cox proportional hazard models. Median CA 125 levels were significantly higher in HFpEF patients compared with controls [CA 125: 23.5 (14.5-44.7) vs. 14.6 (10.3-21.0) U/mL, P = 0.004]. CA 125 levels were positively correlated with a congestion marker [N-terminal pro-brain natriuretic peptide (NT-proBNP) levels, Pearson's r = 0.37, P < 0.001] and markers of cardiac fibrosis estimated by both ECV (Pearson's r = 0.26, P = 0.003) and fibroblast growth factor 23 levels (Pearson's r = 0.50, P < 0.001). Over a median follow-up of 49 (22-64) months, 97 HFpEF patients reached the composite endpoint. Even after adjustment for the Meta-Analysis Global Group in Chronic risk score, a CA 125 level ≥35 U/mL was still a significant predictor of the composite endpoint [hazard ratio (HR): 1.58 (1.04-2.41), P = 0.032] and more particularly of HF hospitalization [HR: 1.81 (1.13-2.92), P = 0.014]. In contrast, NT-proBNP levels were not an independent predictor. CONCLUSIONS: CA 125 levels were significantly higher in HFpEF patients compared with controls matched for age and sex and were associated with markers of congestion and cardiac fibrosis. CA 125 levels were a strong and independent predictor of HF hospitalization in HFpEF patients. These data suggest a potential value of CA 125 as a biomarker for staging and risk prediction in HFpEF.

Review and critical appraisal of the indications for cardiac magnetic resonance imaging in the ESC guidelines.

Cardiac MRI has made significant advances in the past decade, becoming an important technique for the evaluation of various cardiac pathologies. The aim of this document is to review the current indications for performing cardiac MRI based on the current ESC guidelines for STEMI, NSTEMI, chronic coronary artery disease, heart failure, arrhythmias, sudden cardiac death, valvular heart disease, pericardial disease and congenital heart disease. The review discusses the diagnostic and prognostic value of cMR for numerous cardiac diseases, and its important value in assessing structural heart disease and predicting arrhythmia risk. Additionally, it reflects upon the appropriateness of the guidelines and points out areas where the indications should be revised in future editions, based on the author's personal opinion. It is suggested that guideline criteria for the use of cMR should be more explicit to promote its use and lead to more specific reimbursements. However, further studies are needed to even better document the value of cMR in the future.

Cardiac structure, function, and coronary anatomy 10 years after isolated contemporary adjuvant radiotherapy in breast cancer patients with low cardiovascular baseline risk.

AIMS: The effects of isolated contemporary low-dose breast cancer (BC) radiotherapy (RT) on the heart remain poorly understood. This study aims to assess the long-term impacts of BC-RT on cardiac structure and function. METHODS AND RESULTS: Seventy-six women (62 ± 7 years) without history of prior heart disease, who had undergone RT for either first left (n = 36) or right (n = 40) BC, without additional medical oncology therapy apart from hormonal treatment 11 ± 1 years earlier, underwent transthoracic echocardiography, cardiac magnetic resonance imaging (CMR), computed tomography coronary angiography (CTCA), NT-proBNP, and a 6-min walk test (6MWT). They were compared with 54 age-matched healthy female controls. By CTCA, 68% of BC patients exhibited no or very mild coronary disease, while only 11% had moderate stenosis (50-69%) and 3% had significant stenosis (>70%). Despite slightly reduced regional echocardiographic midventricular strains, BC patients exhibited similar global left and right ventricular volumes, ejection fractions, and global strains by echocardiography and CMR as controls. Mitral E/e' ratios were slightly higher, and mitral deceleration times were slightly lower, but NT-proBNP was similar to controls. Also, 6MWT was normal. None had late gadolinium enhancement, and extracellular volume fraction was similar in BC (28 ± 3 vs. 29 ± 3, P = 0.15) and controls. No differences were observed relative to dose or side of RT. CONCLUSION: Aside from minor alterations of regional strains and diastolic parameters, women who received isolated RT for BC had low prevalence of coronary disease, normal global systolic function, NT-proBNP, and exercise capacity and showed no structural changes by CMR, refuting significant long-term cardiotoxicity in such low-risk patients.

Impact of early versus class I-triggered surgery on postoperative survival in severe aortic regurgitation: An observational study from the Aortic Valve Insufficiency and Ascending Aorta Aneurysm International Registry.

OBJECTIVES: Class I triggers for severe and chronic aortic regurgitation surgery mainly rely on symptoms or systolic dysfunction, resulting in a negative outcome despite surgical correction. Therefore, US and European guidelines now advocate for earlier surgery. We sought to determine whether earlier surgery leads to improved postoperative survival. METHODS: We evaluated the postoperative survival of patients who underwent surgery for severe aortic regurgitation in the international multicenter registry for aortic valve surgery, Aortic Valve Insufficiency and Ascending Aorta Aneurysm International Registry, over a median follow-up of 37 months. RESULTS: Among 1899 patients (aged 49 ± 15 years, 85% were male), 83% and 84% had class I indication according to the American Heart Association and European Society of Cardiology, respectively, and most were offered repair surgery (92%). Twelve patients (0.6%) died after surgery, and 68 patients died within 10 years after the procedure. Heart failure symptoms (hazard ratio, 2.60 [1.20-5.66], P = .016) and either left ventricular end-systolic diameter greater than 50 mm or left ventricular end-systolic diameter index greater than 25 mm/m2 (hazard ratio, 1.64 [1.05-2.55], P = .030) predicted survival independently over and above age, gender, and bicuspid phenotype. Therefore, patients who underwent surgery based on any class I trigger had worse adjusted survival. However, patients who underwent surgery while meeting early imaging triggers (left ventricular end-systolic diameter index 20-25 mm/m2 or left ventricular ejection fraction 50% to 55%) had no significant outcome penalty. CONCLUSIONS: In this international registry of severe aortic regurgitation, surgery when meeting class I triggers led to postoperative outcome penalty compared with earlier triggers (left ventricular end-systolic diameter index 20-25 mm/m2 or ventricular ejection fraction 50%-55%). This observation, which applies to expert centers where aortic valve repair is feasible, should encourage the global use of repair techniques and the conduction of randomized trials.

Designed Loop Extension Followed by Combinatorial Screening Confers High Specificity to a Broad Matrix MetalloproteinaseInhibitor.

Matrix metalloproteinases (MMPs) are key drivers of various diseases, including cancer. Development of probes and drugs capable of selectively inhibiting the individual members of the large MMP family remains a persistent challenge. The inhibitory N-terminal domain of tissue inhibitor of metalloproteinases-2 (N-TIMP2), a natural broad MMP inhibitor, can provide a scaffold for protein engineering to create more selective MMP inhibitors. Here, we pursued a unique approach harnessing both computational design and combinatorial screening to confer high binding specificity toward a target MMP in preference to an anti-target MMP. We designed a loop extension of N-TIMP2 to allow new interactions with the non-conserved MMP surface and generated an efficient focused library for yeast surface display, which was then screened for high binding to the target MMP-14 and low binding to anti-target MMP-3. Deep sequencing analysis identified the most promising variants, which were expressed, purified, and tested for selectivity of inhibition. Our best N-TIMP2 variant exhibited 29 pM binding affinity to MMP-14 and 2.4 µM affinity to MMP-3, revealing 7500-fold greater specificity than WT N-TIMP2. High-confidence structural models were obtained by including NGS data in the AlphaFold multiple sequence alignment. The modeling together with experimental mutagenesis validated our design predictions, demonstrating that the loop extension packs tightly against non-conserved residues on MMP-14 and clashes with MMP-3. This study demonstrates how introduction of loop extensions in a manner guided by target protein conservation data and loop design can offer an attractive strategy to achieve specificity in design of protein ligands.

Strength of a cement-based dental material: Early age testing and first micromechanical modeling at mature age.

The compressive strength evolution of 37 centigrade-cured Biodentine, a cement-based dental material, is quantified experimentally by crushing cylindrical specimens with length-to-diameter ratios amounting to 1.84 and 1.34, respectively, at nine different material ages ranging from 1 h to 28 days. After excluding strength values significantly affected by imperfections, formulae developed for concrete are i) adapted for inter- and extrapolation of measured strength values, and ii) used for quantification of the influence of the slenderness of the specimens on the compressive strength. The microscopic origin of the macroscopic uniaxial compressive strength of mature Biodentine is investigated by means of a micromechanics model accounting for lognormal stiffness and strength distributions of two types of calcite-reinforced hydrates. The following results are obtained: The material behavior of Biodentine is non-linear in the first few hours after production. After that, Biodentine behaves virtually linear elastic all the way up to sudden brittle failure. The strength evolution of Biodentine can be well described as the exponential of a function involving the square root of the inverse of the material age. The genuine uniaxial compressive strength evolution can be quantified using a correction formula taken from a standard for testing of concrete, which accounts for length-to-diameter ratios of cylindrical samples deviating from 2. Multiscale modeling suggests that 63% of the overall material volume, occupied by dense calcite-reinforced hydration products, fail virtually simultaneously. This underlines the highly optimized nature of the studied material.

Quantification of primary mitral regurgitation by echocardiography: A practical appraisal.

The accurate quantification of primary mitral regurgitation (MR) and its consequences on cardiac remodeling is of paramount importance to determine the best timing for surgery in these patients. The recommended echocardiographic grading of primary MR severity relies on an integrated multiparametric approach. It is expected that the large number of echocardiographic parameters collected would offer the possibility to check the measured values regarding their congruence in order to conclude reliably on MR severity. However, the use of multiple parameters to grade MR can result in potential discrepancies between one or more of them. Importantly, many factors beyond MR severity impact the values obtained for these parameters including technical settings, anatomic and hemodynamic considerations, patient's characteristics and echocardiographer' skills. Hence, clinicians involved in valvular diseases should be well aware of the respective strengths and pitfalls of each of MR grading methods by echocardiography. Recent literature highlighted the need for a reappraisal of the severity of primary MR from a hemodynamic perspective. The estimation of MR regurgitation fraction by indirect quantitative methods, whenever possible, should be central when grading the severity of these patients. The assessment of the MR effective regurgitant orifice area by the proximal flow convergence method should be used in a semi-quantitative manner. Furthermore, it is crucial to acknowledge specific clinical situations in MR at risk of misevaluation when grading severity such as late-systolic MR, bi-leaflet prolapse with multiple jets or extensive leak, wall-constrained eccentric jet or in older patients with complex MR mechanism. Finally, it is debatable whether the 4-grades classification of MR severity would be still relevant nowadays, since the indication for mitral valve (MV) surgery is discussed in clinical practice for patients with 3+ and 4+ primary MR based on symptoms, specific markers of adverse outcome and MV repair probability. Primary MR grading should be seen as a continuum integrating both quantification of MR and its consequences, even for patients with presumed "moderate" MR.

The year 2021 in the European Heart Journal: Cardiovascular Imaging Part II.

The European Heart Journal-Cardiovascular Imaging was launched in 2012 and has during these years become one of the leading multimodality cardiovascular imaging journals. The journal is currently ranked as Number 19 among all cardiovascular journals. It has an impressive impact factor of 9.130. The most important studies published in our Journal from 2021 will be highlighted in two reports. Part II will focus on valvular heart disease, heart failure, cardiomyopathies, and congenital heart disease, while Part I of the review has focused on studies about myocardial function and risk prediction, myocardial ischaemia, and emerging techniques in cardiovascular imaging.

Usage of a graph database for the selection of sterile items in the OR.

PURPOSE: In this work, we present a subsystem of a robotic circulating nurse, that produces recommendations for the next supplied sterile item based on incomplete requests from the sterile OR staff, the current situation, predefined knowledge and experience from previous surgeries. We describe a structure to store and query the underlying information in terms of entities and their relationships of varying strength. METHODS: For the implementation, the graph database Neo4j is used as a core component together with its querying language Cypher. We outline a specific structure of nodes and relationships, i.e., a graph. Primarily, it allows to represent entities like surgeons, surgery types and items, as well as their complex interconnectivity. In addition, it enables to match given situations and partial requests in the OR with corresponding subgraphs. The subgraphs provide suitable sterile items and allow to prioritize them according to their utilization frequency. RESULTS: The graph database was populated with existing data from 854 surgeries describing the intraoperative use of sterile items. A test scenario is evaluated in which a request for "Prolene" is made during a cholecystectomy. The software identifies a specific "Prolene" suture material as the most probable requested sterile item, because of its utilization frequency from over 95%. Other "Prolene" suture materials were used in less than 15% of the cholecystectomies. CONCLUSION: We have proposed a graph database for the selection of sterile items in the operating room. The example shows how the partial information from different sources can be easily integrated in a query, leading to an unique result. Eventually, we propose possible enhancements to further improve the quality of the recommendations. In the next step, the recommendations of the software will be evaluated in real time during surgeries.

Prediction of Left Atrial Fibrosis and Success of Catheter Ablation by Speckle Tracking Echocardiography in Patients Imaged in Persistent Atrial Fibrillation.

Background: Non-invasive evaluation of left atrial structural and functional remodeling should be considered in all patients with persistent atrial fibrillation (AF) to optimal management. Speckle tracking echocardiography (STE) has been shown to predict AF recurrence after catheter ablation; however in most studies, patients had paroxysmal AF, and STE was performed while patients were in sinus rhythm. Aim: The aim of this study was to evaluate the ability of STE parameters acquired during persistent AF to assess atrial fibrosis measured by low voltage area, and to predict maintenance of sinus rhythm of catheter ablation. Methods: A total of 94 patients (69 men, 65 ± 9 years) with persistent AF prospectively underwent measurement of Global Peak Atrial Longitudinal Strain (GPALS), indexed LA Volume (LAVI), E/e' ratio, and LA stiffness index (the ratio of E/e' to GPALS) by STE prior to catheter ablation, while in AF. Low-voltage area (LVA) was assessed by electro-anatomical mapping and categorized into absent, moderate (>0 to <15%), and high (≥15%) atrial extent. AF recurrence was evaluated after 3 months of blanking. Results: Multivariable regression showed that LAVI, GPALS, and LA stiffness independently predicted LVA extent after correcting for age, glomerular filtration rate, and CHA2DS2-VASc score. Of all the parameters, LA stiffness index had the highest diagnostic accuracy (AUC 0.85), allowing using a cut-off value ≥0.7 to predict moderate or high LVA with 88% sensitivity and 47% specificity, respectively. In multivariable Cox analysis, both GPALS and LA stiffness were able to significantly improve the c statistic to predict AF recurrence (n = 40 over 9 months FU) over CHARGE-AF (p < 0.001 for GPALS and p = 0.01 for LA stiffness) or CHA2DS2-VASc score (p < 0.001 for GPALS and p = 0.02 for LA stiffness). GPALS and LA stiffness also improved the net reclassification index (NRI) over the CHARGE-AF index (NRI 0.67, 95% CI [0.33-1.13] for GPALS and NRI 0.73, 95% CI [0.12-0.91] for LA stiffness, respectively), and over the CHA2DS2-VASc score (NRI 0.43, 95% CI [-0.14 to 0.69] for GPALS and NRI 0.52, 95% CI [0.10-0.84], respectively) for LA stiffness to predict AF recurrence at 9 months. Conclusion: STE parameters acquired during AF allow prediction of LVA extent and AF recurrence in patients with persistent AF undergoing catheter ablation. Therefore, STE could be a valuable approach to select candidates for catheter ablation.

Motion Estimation by Deep Learning in 2D Echocardiography: Synthetic Dataset and Validation.

Motion estimation in echocardiography plays an important role in the characterization of cardiac function, allowing the computation of myocardial deformation indices. However, there exist limitations in clinical practice, particularly with regard to the accuracy and robustness of measurements extracted from images. We therefore propose a novel deep learning solution for motion estimation in echocardiography. Our network corresponds to a modified version of PWC-Net which achieves high performance on ultrasound sequences. In parallel, we designed a novel simulation pipeline allowing the generation of a large amount of realistic B-mode sequences. These synthetic data, together with strategies during training and inference, were used to improve the performance of our deep learning solution, which achieved an average endpoint error of 0.07 ± 0.06 mm per frame and 1.20 ± 0.67 mm between ED and ES on our simulated dataset. The performance of our method was further investigated on 30 patients from a publicly available clinical dataset acquired from a GE system. The method showed promise by achieving a mean absolute error of the global longitudinal strain of 2.5 ± 2.1% and a correlation of 0.77 compared to GLS derived from manual segmentation, much better than one of the most efficient methods in the state-of-the-art (namely the FFT-Xcorr block-matching method). We finally evaluated our method on an auxiliary dataset including 30 patients from another center and acquired with a different system. Comparable results were achieved, illustrating the ability of our method to maintain high performance regardless of the echocardiographic data processed.

Multimodality imaging in patients with heart failure and preserved ejection fraction: an expert consensus document of the European Association of Cardiovascular Imaging.

Nearly half of all patients with heart failure (HF) have a normal left ventricular (LV) ejection fraction (EF) and the condition is termed heart failure with preserved ejection fraction (HFpEF). It is assumed that in these patients HF is due primarily to LV diastolic dysfunction. The prognosis in HFpEF is almost as severe as in HF with reduced EF (HFrEF). In contrast to HFrEF where drugs and devices are proven to reduce mortality, in HFpEF there has been limited therapy available with documented effects on prognosis. This may reflect that HFpEF encompasses a wide range of different pathological processes, which multimodality imaging is well placed to differentiate. Progress in developing therapies for HFpEF has been hampered by a lack of uniform diagnostic criteria. The present expert consensus document from the European Association of Cardiovascular Imaging (EACVI) provides recommendations regarding how to determine elevated LV filling pressure in the setting of suspected HFpEF and how to use multimodality imaging to determine specific aetiologies in patients with HFpEF.