Physiologic Range of Myocardial Mechano-Energetic Efficiency among Healthy Subjects: Impact of Gender and Age.

BACKGROUND: Myocardial mechano-energetic efficiency (MEE) is the capability of the left ventricle (LV) to convert the chemical energy obtained from the cardiac oxidative metabolism into mechanical work. The aim of present study was to establish normal non-invasive MEE and MEEi reference values. METHODS: In total, 1168 healthy subjects underwent physical examinations, clinical assessment, and standardized transthoracic echocardiographic (TTE) examination. MEE was obtained by TTE as the ratio between stroke volume (SV) and heart rate (HR): MEE = SV/HR [HR expressed in seconds (HR/60)]. Because MEE is highly related to left ventricular mass (LVM), MEE was then divided by LVM with the purpose of obtaining an estimate of energetic expenditure per unit of myocardial mass (i.e., indexed MEE, MEEi, mL/s/g). RESULTS: The mean values of MEE and MEEi in the overall population were 61.09 ± 18.19 mL/s; 0.45 ± 0.14, respectively. In a multivariable analysis, gender, body surface area (BSA), diastolic blood pressure, left atrial volume indexed to BSA, E/e' and tricuspid annular plane systolic excursion (TAPSE) were the independent variables associated with MEE, while age, gender, BSA and TAPSE were the independent variables associated with MEEi. CONCLUSIONS: The knowledge of age- and gender-based MEE and MEEi normal values may improve the global assessment of LV cardiac mechanics and serve as a reference to identify phenotypes at high risk of cardiovascular events.

Right Heart Pulmonary Circulation Unit Response to Exercise in Patients with Controlled Systemic Arterial Hypertension: Insights from the RIGHT Heart International NETwork (RIGHT-NET).

BACKGROUND: Systemic arterial hypertension (HTN) is the main risk factor for the development of heart failure with preserved ejection fraction (HFpEF). The aim of the study was was to assess the trends in PASP, E/E' and TAPSE during exercise Doppler echocardiography (EDE) in hypertensive (HTN) patients vs. healthy subjects stratified by age. METHODS: EDE was performed in 155 hypertensive patients and in 145 healthy subjects (mean age 62 ± 12.0 vs. 54 ± 14.9 years respectively, p < 0.0001). EDE was undertaken on a semi-recumbent cycle ergometer with load increasing by 25 watts every 2 min. Left ventricular (LV) and right ventricular (RV) dimensions, function and hemodynamics were evaluated. RESULTS: Echo-Doppler parameters of LV and RV function were lower, both at rest and at peak exercise in hypertensives, while pulmonary hemodynamics were higher as compared to healthy subjects. The entire cohort was then divided into tertiles of age: at rest, no significant differences were recorded for each age group between hypertensives and normotensives except for E/E' that was higher in hypertensives. At peak exercise, hypertensives had higher pulmonary artery systolic pressure (PASP) and E/E' but lower tricuspid annular plane systolic excursion (TAPSE) as age increased, compared to normotensives. Differences in E/E' and TAPSE between the 2 groups at peak exercise were explained by the interaction between HTN and age even after adjustment for baseline values (p < 0.001 for E/E', p = 0.011 for TAPSE). At peak exercise, the oldest group of hypertensive patients had a mean E/E' of 13.0, suggesting a significant increase in LV diastolic pressure combined with increased PASP. CONCLUSION: Age and HTN have a synergic negative effect on E/E' and TAPSE at peak exercise in hypertensive subjects.

Reference Ranges of Left Ventricular Hemodynamic Forces in Healthy Adults: A Speckle-Tracking Echocardiographic Study.

BACKGROUND: The normal limits of left ventricular (LV) hemodynamic forces (HDFs) are not exactly known. The aim of this study was to explore the full spectrum of HDF parameters in healthy subjects and determine their physiologic correlates. METHODS: 269 healthy subjects were enrolled (mean age: 43 ± 14 years; 123 (45.7%) men). All participants underwent an echo-Doppler examination. Tri-plane tissue tracking from apical views was used to measure 2D global endocardial longitudinal strain (GLS), circumferential strain (GCS), and LV HDFs. HDFs were normalized with LV volume and divided by specific weight. RESULTS: LV systolic longitudinal HDFs (%) were higher in men (20.8 ± 6.5 vs. 18.9 ± 5.6, p = 0.009; 22.0 ± 6.7 vs. 19.8 ± 5.6, p = 0.004, respectively). There was a significant correlation between GCS (increased) (r = -0.240, p < 0.001) and LV longitudinal HDFs (reduced) (r = -0.155, p = 0.01) with age. In a multivariable analysis age, BSA, pulse pressure, heart rate and GCS were the only independent variables associated with LV HDFs (ß coefficient = -0.232, p < 0.001; 0.149, p = 0.003; 0.186, p < 0.001; 0.396, p < 0.001; -0.328, p < 0.001; respectively). CONCLUSION: We report on the physiologic range of LV HDFs. Knowledge of reference values of HDFs may prompt their implementation into clinical routine and allow a more comprehensive assessment of the LV function.

Preoperative Assessment and Management of Cardiovascular Risk in Patients Undergoing Non-Cardiac Surgery: Implementing a Systematic Stepwise Approach during the COVID-19 Pandemic Era.

Major adverse cardiac events, defined as death or myocardial infarction, are common causes of perioperative mortality and major morbidity in patients undergoing non-cardiac surgery. Reduction of perioperative cardiovascular risk in relation to non-cardiac surgery requires a stepwise patient evaluation that integrates clinical risk factors, functional status and the estimated stress of the planned surgical procedure. Major guidelines on preoperative cardiovascular risk assessment recommend to establish, firstly, the risk of surgery per se (low, moderate, high) and the related timing (elective vs. urgent/emergent), evaluate the presence of unstable cardiac conditions or a recent coronary revascularization (percutaneous coronary intervention or coronary artery bypass grafting), assess the functional capacity of the patient (usually expressed in metabolic equivalents), determine the value of non-invasive and/or invasive cardiovascular testing and then combine these data in estimating perioperative risk for major cardiac adverse events using validated scores (Revised Cardiac Risk Index (RCRI) or National Surgical Quality Improvement Program (NSQIP)). This stepwise approach has the potential to guide clinicians in determining which patients could benefit from cardiovascular therapy and/or coronary artery revascularization before non-cardiac surgery towards decreasing the incidence of perioperative morbidity and mortality. Finally, it should be highlighted that there is a need to implement specific strategies in the 2019 Coronavirus disease (COVID-19) pandemic to minimize the risk of transmission of COVID-19 infection during the preoperative risk assessment process.

A giant mediastinal teratoma: From diagnosis to complete resection and restitutio ad integrum.

The current report highlights the integrated work-up of an unexpected giant mediastinal teratoma in 28 years old female. A comprehensive multi-modality imaging approach was implemented in order to define the diagnosis and tailor the most appropriate surgical intervention.

[An unusual case of Takotsubo syndrome after dipyridamole stress echocardiography]. / Uno strano caso di sindrome Takotsubo dopo eco-stress con dipiridamolo.

Takotsubo syndrome is a transient form of left ventricular dysfunction, more common in postmenopausal women, which involves left ventricular mid-apical akinesis and mimics acute coronary syndrome. It is characterized by left ventricular apical ballooning without significant coronary artery stenosis on coronary angiography. The basic mechanisms of Takotsubo cardiomyopathy are still unclear. There is some evidence that emotional, physical or pharmacological stress associated with increased catecholamine levels, coronary spasm, dynamic left ventricular obstruction, or coronary microvascular dysfunction might be involved. We describe the case of an 81-year-old woman who developed a Takotsubo syndrome only 3 h after pharmacological stress echocardiography with dipyridamole. To our knowledge, this is the first case reported in the literature in such context.

Predictors of in-hospital and long-term mortality in unselected patients admitted to a modern coronary care unit.

AIMS: Objective data on epidemiology, management and outcome of patients with acute cardiac illness are still scarce, and producing evidence-based guidelines remains an issue. In order to define the clinical characteristics and the potential predictors of in-hospital and long-term mortality, we performed a retrospective, observational study, in a tertiary cardiac centre in Italy. METHODS: One thousand one hundred and sixty-five consecutive patients, admitted to our intensive cardiac care unit (ICCU) during the year 2016, were included in the study. The data were collected from the hospital discharge summary and the electronic chart records. RESULTS: Global in-hospital mortality was 7.2%. Predictors of in-hospital mortality were age [odds ratio (OR): 2.0; P = 0.011], female sex (OR: 2.18; P = 0.003), cardiac arrest (OR: 12.21; P = 0.000), heart failure/cardiogenic shock (OR: 9.99; P = 0.000), sepsis/septic shock (OR: 5.54; P = 0.000), acute kidney injury (OR: 3.25; P = 0.021) and a primary diagnosis of acute heart failure or a condition other than acute heart failure and acute coronary syndrome. During a mean follow-up period of 17.4 ± 4.8 months, 96 all-cause deaths occurred in patients who were still alive at discharge. One-year mortality rate was 8.2%. Predictors of long-term mortality were age (hazard ratio: 1.08; P = 0.000), female sex (hazard ratio: 0.59; P = 0.022), comorbidity at least 3 (hazard ratio: 1,60; P = 0.047), acute kidney injury (hazard ratio: 3.15; P = 0.001), inotropic treatment (hazard ratio: 2.54; P = 0.002) and a primary diagnosis of acute heart failure. CONCLUSION: In our Level-2 ICCU, predictors of in-hospital and long-term mortality are similar to those commonly found in a Level-3 ICU. These data strongly suggest that ICUs dealing with acute cardiovascular patients should be reorganized with a necessary upgrading of competences and resources for medical and nursing staff.

Joint registration and synthesis using a probabilistic model for alignment of MRI and histological sections.

Nonlinear registration of 2D histological sections with corresponding slices of MRI data is a critical step of 3D histology reconstruction algorithms. This registration is difficult due to the large differences in image contrast and resolution, as well as the complex nonrigid deformations and artefacts produced when sectioning the sample and mounting it on the glass slide. It has been shown in brain MRI registration that better spatial alignment across modalities can be obtained by synthesising one modality from the other and then using intra-modality registration metrics, rather than by using information theory based metrics to solve the problem directly. However, such an approach typically requires a database of aligned images from the two modalities, which is very difficult to obtain for histology and MRI. Here, we overcome this limitation with a probabilistic method that simultaneously solves for deformable registration and synthesis directly on the target images, without requiring any training data. The method is based on a probabilistic model in which the MRI slice is assumed to be a contrast-warped, spatially deformed version of the histological section. We use approximate Bayesian inference to iteratively refine the probabilistic estimate of the synthesis and the registration, while accounting for each other's uncertainty. Moreover, manually placed landmarks can be seamlessly integrated in the framework for increased performance and robustness. Experiments on a synthetic dataset of MRI slices show that, compared with mutual information based registration, the proposed method makes it possible to use a much more flexible deformation model in the registration to improve its accuracy, without compromising robustness. Moreover, our framework also exploits information in manually placed landmarks more efficiently than mutual information: landmarks constrain the deformation field in both methods, but in our algorithm, it also has a positive effect on the synthesis - which further improves the registration. We also show results on two real, publicly available datasets: the Allen and BigBrain atlases. In both of them, the proposed method provides a clear improvement over mutual information based registration, both qualitatively (visual inspection) and quantitatively (registration error measured with pairs of manually annotated landmarks).

Bailout surgical explantation of a transcatheter valve-in-valve for subacute thrombosis: When there is no time for anticoagulation: Case report and literature review.

Trancatheter heart valve (THV) thrombosis is effectively treated with anticoagulation but alternative therapies are required when a faster gradient reduction is needed. Open heart surgery has been rarely performed due to the high perioperative mortality and only five cases have been described so far. Here we describe a case of emergent surgical explantation for THV thrombosis after a valve-in-valve. A 67years old man underwent transcatheter aortic valve implantation for a failed surgical bioprosthesis Epic 21mm (St. Jude Medical; St. Paul, Minnesota, US). A CoreValve 23mm (Medtronic, Minneapolis, Minnesota, US) was implanted through femoral access under conscious sedation without complications. Mean transvalvular gradient was effectively reduced (33mmHg vs 16mmHg) with no more than mild residual aortic regurgitation. After 8days the patient was discharged on dual antiplatelet therapy but was readmitted to the intensive care unit for pulmonary oedema 13days later. Echocardiography showed a raised transvalvular mean gradient (mean gradient change from discharge=15mmHg) without aortic regurgitation. Heart Team decided for emergent open heart surgery for the hemodynamic instability. On direct inspection THV was well positioned inside the surgical bioprosthesis but two cusps were covered by thrombus which markedly restricted their mobility. The THV and the former surgical valve were explanted and a new larger stented bioprosthesis was implanted. Thrombosis of the THV was confirmed on microscopic examination which showed no signs of inflammation or degeneration. The patient was discharged after 1month and the 3month follow up showed stable transvalvular gradients.

TAVI for Failed Valve-Sparing Operations: In-Hospital and Mid-Term Outcome.

BACKGROUND AND AIM OF THE STUDY: Although transcatheter aortic valve implantation (TAVI) is a steadily expanding treatment for the pathology of the aortic valve, its role in the replacement of native aortic valves following valve-sparing surgery has not been investigated. METHODS: Among 150 patients who underwent TAVI at the authors' institution, three (2%) had a failed valve-sparing operation. The in-hospital outcome, mid-term mortality, and valvular function of the three patients were evaluated retrospectively. These patients, who were deemed at high surgical risk by the heart team, underwent TAVI for predominant severe aortic stenosis (n = 2) or pure severe aortic regurgitation (AR) (n = 1). RESULTS: A self-expandable CoreValve prosthesis was inserted via femoral access in all three patients. Based on the Valve Academic Research Consortium 2 criteria (VARC-2), implantation was successful in all cases, with only one major access site complication and no more than mild residual AR. At a follow up of 13 ± 6 months there were no deaths and the mean transvalvular gradient remained low (7 ± 6 mmHg at discharge; 7 ± 4 mmHg at follow up), without any echocardiographic signs of valve deterioration. CONCLUSIONS: The results obtained with this small patient cohort demonstrated the feasibility, safety, and favorable mid-term outcomes of TAVI for failed valve-sparing operations in high surgical risk patients. However, these findings must be validated in larger cohorts before extending such treatment routinely to this subset of patients.

A fully automated tortuosity quantification system with application to corneal nerve fibres in confocal microscopy images.

Recent clinical research has highlighted important links between a number of diseases and the tortuosity of curvilinear anatomical structures like corneal nerve fibres, suggesting that tortuosity changes might detect early stages of specific conditions. Currently, clinical studies are mainly based on subjective, visual assessment, with limited repeatability and inter-observer agreement. To address these problems, we propose a fully automated framework for image-level tortuosity estimation, consisting of a hybrid segmentation method and a highly adaptable, definition-free tortuosity estimation algorithm. The former combines an appearance model, based on a Scale and Curvature-Invariant Ridge Detector (SCIRD), with a context model, including multi-range learned context filters. The latter is based on a novel tortuosity estimation paradigm in which discriminative, multi-scale features can be automatically learned for specific anatomical objects and diseases. Experimental results on 140 in vivo confocal microscopy images of corneal nerve fibres from healthy and unhealthy subjects demonstrate the excellent performance of our method compared to state-of-the-art approaches and ground truth annotations from 3 expert observers.

Accelerating Convolutional Sparse Coding for Curvilinear Structures Segmentation by Refining SCIRD-TS Filter Banks.

Deep learning has shown great potential for curvilinear structure (e.g., retinal blood vessels and neurites) segmentation as demonstrated by a recent auto-context regression architecture based on filter banks learned by convolutional sparse coding. However, learning such filter banks is very time-consuming, thus limiting the amount of filters employed and the adaptation to other data sets (i.e., slow re-training). We address this limitation by proposing a novel acceleration strategy to speed-up convolutional sparse coding filter learning for curvilinear structure segmentation. Our approach is based on a novel initialisation strategy (warm start), and therefore it is different from recent methods improving the optimisation itself. Our warm-start strategy is based on carefully designed hand-crafted filters (SCIRD-TS), modelling appearance properties of curvilinear structures which are then refined by convolutional sparse coding. Experiments on four diverse data sets, including retinal blood vessels and neurites, suggest that the proposed method reduces significantly the time taken to learn convolutional filter banks (i.e., up to -82%) compared to conventional initialisation strategies. Remarkably, this speed-up does not worsen performance; in fact, filters learned with the proposed strategy often achieve a much lower reconstruction error and match or exceed the segmentation performance of random and DCT-based initialisation, when used as input to a random forest classifier.

Two-Dimensional Plane for Multi-Scale Quantification of Corneal Subbasal Nerve Tortuosity.

PURPOSE: To assess the performance of a novel system for automated tortuosity estimation and interpretation. METHODS: A supervised strategy (driven by observers' grading) was employed to automatically identify the combination of tortuosity measures (i.e., tortuosity representation) leading to the best agreement with the observers. We investigated 18 tortuosity measures including curvature and density of inflection points, computed at multiple spatial scales. To leverage tortuosity interpretation, we propose the tortuosity plane (TP) onto which each image is mapped. Experiments were carried out on 140 images of subbasal nerve plexus of the central cornea, covering four levels of tortuosity. Three experienced observers graded each image independently. RESULTS: The best tortuosity representation was the combination of mean curvature at spatial scales 2 and 5. These tortuosity measures were the axes of the proposed TP (interpretation). The system for tortuosity estimation revealed strong agreement with the observers on a global and per-level basis. The agreement with each observer (Spearman's correlation) was statistically significant (αs = 0.05, P < 0.0001) and higher than that of at least one of the other observers in two out of three cases (ρOUR = 0.7594 versus ρObs3 = 0.7225; ρOUR = 0.8880 versus ρObs1 = 0.8017, ρObs3 = 0.7315). Based on paired-sample t-tests, these improvements were significant (P < 0.001). CONCLUSIONS: Our automated system stratifies images by four tortuosity levels (discrete scale) matching or exceeding the accuracy of experienced observers. Of importance, the TP allows the assessment of tortuosity on a two-dimensional continuous scale, thus leading to a finer discrimination among images.

Leveraging Multiscale Hessian-Based Enhancement With a Novel Exudate Inpainting Technique for Retinal Vessel Segmentation.

Accurate vessel detection in retinal images is an important and difficult task. Detection is made more challenging in pathological images with the presence of exudates and other abnormalities. In this paper, we present a new unsupervised vessel segmentation approach to address this problem. A novel inpainting filter, called neighborhood estimator before filling, is proposed to inpaint exudates in a way that nearby false positives are significantly reduced during vessel enhancement. Retinal vascular enhancement is achieved with a multiple-scale Hessian approach. Experimental results show that the proposed vessel segmentation method outperforms state-of-the-art algorithms reported in the recent literature, both visually and in terms of quantitative measurements, with overall mean accuracy of 95.62% on the STARE dataset and 95.81% on the HRF dataset.

Combining efficient hand-crafted features with learned filters for fast and accurate corneal nerve fibre centreline detection.

We propose a new approach to corneal nerve fibre centreline detection for in vivo confocal microscopy images. Relying on a combination of efficient hand-crafted features and learned filters, our method offers an excellent compromise between accuracy and running time. Unlike previous solutions using sparse coding to learn small filter banks, we employ K-means to efficiently learn the high amount of filters needed to cope with the multiple challenges involved, e.g., low contrast and resolution, non-uniform illumination, tortuosity and confounding non-target structures. The use of K-means for dictionary learning allows us to learn banks of 100 filters in less than 30 seconds compared to several days needed when using sparse coding. Experimental results using a dataset including 100 images show that our approach outperforms significantly state-of-the-art methods in terms of precision-recall curves.

Targeting mitochondria as therapeutic strategy for metabolic disorders.

Mitochondria are critical regulator of cell metabolism; thus, mitochondrial dysfunction is associated with many metabolic disorders. Defects in oxidative phosphorylation, ROS production, or mtDNA mutations are the main causes of mitochondrial dysfunction in many pathological conditions such as IR/diabetes, metabolic syndrome, cardiovascular diseases, and cancer. Thus, targeting mitochondria has been proposed as therapeutic approach for these conditions, leading to the development of small molecules to be tested in the clinical scenario. Here we discuss therapeutic interventions to treat mitochondrial dysfunction associated with two major metabolic disorders, metabolic syndrome, and cancer. Finally, novel mechanisms of regulation of mitochondrial function are discussed, which open new scenarios for mitochondria targeting.

An experimental assessment of five indices of retinal vessel tortuosity with the RET-TORT public dataset.

We compare the performance of five indices of retinal vessel tortuosity against sampling rates of vessel centerlines. We consider distance measure, tortuosity density, two curvature-based measures, and a recently introduced slope-chain coding for general curves, never before assessed comparatively with retinal vessels. To enable replication of our results, we use the public dataset for retinal tortuosity, RET-TORT. We find that (1) the tortuosity density index offers good performance overall, but is not always the best performer; (2) curvature-based methods are the best if high-frequency resampling is possible, but (3) are the most sensitive to variations of the number of samples; (4) slope-chain coding performs best at low sampling rates, but the length of the linear elements must be chosen carefully. In general, performance may vary considerably with resampling, suggesting that the choice of a tortuosity index for clinical inference requires attention to numerical details, and ideally standardization thereof.

Endothelial G protein-coupled receptor kinase 2 regulates vascular homeostasis through the control of free radical oxygen species.

OBJECTIVE: The role of endothelial G protein-coupled receptor kinase 2 (GRK2) was investigated in mice with selective deletion of the kinase in the endothelium (Tie2-CRE/GRK2(fl/fl)). APPROACH AND RESULTS: Aortas from Tie2-CRE/GRK2(fl/fl) presented functional and structural alterations as compared with control GRK2(fl/fl) mice. In particular, vasoconstriction was blunted to different agonists, and collagen and elastic rearrangement and macrophage infiltration were observed. In primary cultured endothelial cells deficient for GRK2, mitochondrial reactive oxygen species was increased, leading to expression of cytokines. Chronic treatment with a reactive oxygen species scavenger in mice corrected the vascular phenotype by recovering vasoconstriction, structural abnormalities, and reducing macrophage infiltration. CONCLUSIONS: These results demonstrate that GRK2 removal compromises vascular phenotype and integrity by increasing endothelial reactive oxygen species production.