Microvascular Obstruction in ST-Segment Elevation Myocardial Infarction : Looking Back to Move Forward. Focus on CMR

After a myocardial infarction (MI), despite the resolution of the coronary occlusion, the deterioration of myocardial perfusion persists in a considerable number of patients. This phenomenon is known as microvascular obstruction (MVO). Initially, the focus was placed on re-establishing blood flow in the epicardial artery. Then, the observation that MVO has profound negative structural and prognostic repercussions revived interest in microcirculation. In the near future, the availability of co-adjuvant therapies (beyond timely coronary reperfusion) aimed at preventing, minimizing, and repairing MVOs and finding convincing answers to questions regarding what, when, how, and where to administer these therapies will be of utmost importance. The objective of this work is to review the state-of-the-art concepts on pathophysiology, diagnostic methods, and structural and clinical implications of MVOs in patients with ST-segment elevation MIs. Based on this knowledge we discuss previously-tested and future opportunities for the prevention and repair of MVO

End-systole and end-diastole detection in short axis cine MRI using a fully convolutional neural network with dilated convolutions

[EN] The correct assessment and characterization of heart anatomy and functionality is usually done through inspection of magnetic resonance image cine sequences. In the clinical setting it is especially important to determine the state of the left ventricle. This requires the measurement of its volume in the end-diastolic and end-systolic frames within the sequence trough segmentation methods. However, the first step required for this analysis before any segmentation is the detection of the end-systolic and end-diastolic frames within the image acquisition. In this work we present a fully convolutional neural network that makes use of dilated convolutions to encode and process the temporal information of the sequences in contrast to the more widespread use of recurrent networks that are usually employed for problems involving temporal information. We trained the network in two different settings employing different loss functions to train the network: the classical weighted cross-entropy, and the weighted Dice loss. We had access to a database comprising a total of 397 cases. Out of this dataset we used 98 cases as test set to validate our network performance. The final classification on the test set yielded a mean frame distance of 0 for the end-diastolic frame (i.e.: the selected frame was the correct one in all images of the test set) and 1.242 (relative frame distance of 0.036) for the end-systolic frame employing the optimum setting, which involved training the neural network with the Dice loss. Our neural network is capable of classifying each frame and enables the detection of the end-systolic and end-diastolic frames in short axis cine MRI sequences with high accuracy.Funding sources This work was partially supported by the Conselleria d'Innovació, Universitats, Ciència i Societat Digital, Generalitat Valenciana (grants AEST/2020/029 and AEST/2021/050) .Pérez-Pelegrí, M.; Monmeneu, JV.; López-Lereu, MP.; Maceira, AM.; Bodi, V.; Moratal, D. (2022). End-systole and end-diastole detection in short axis cine MRI using a fully convolutional neural network with dilated convolutions. Computerized Medical Imaging and Graphics. 99:1-8. https://doi.org/10.1016/j.compmedimag.2022.102085189

Automatic left ventricle volume calculation with explainability through a deep learning weak-supervision methodology

[EN] Background and objective: Magnetic resonance imaging is the most reliable imaging technique to assess the heart. More specifically there is great importance in the analysis of the left ventricle, as the main pathologies directly affect this region. In order to characterize the left ventricle, it is necessary to extract its volume. In this work we present a neural network architecture that is capable of directly estimating the left ventricle volume in short axis cine Magnetic Resonance Imaging in the end-diastolic frame and provide a segmentation of the region which is the basis of the volume calculation, thus offering explain-ability to the estimated value. Methods: The network was designed to directly target the volumes to estimate, not requiring any labeled segmentation on the images. The network was based on a 3D U-net with extra layers defined in a scan-ning module that learned features like the circularity of the objects and the volumes to estimate in a weakly-supervised manner. The only targets defined were the left ventricle volumes and the circularity of the object detected through the estimation of the pi value derived from its shape. We had access to 397 cases corresponding to 397 different subjects. We randomly selected 98 cases to use as test set. Results: The results show a good match between the real and estimated volumes in the test set, with a mean relative error of 8% and a mean absolute error of 9.12 ml with a Pearson correlation coefficient of 0.95. The derived segmentations obtained by the network achieved Dice coefficients with a mean value of 0.79. Conclusions: The proposed method is capable of obtaining the left ventricle volume biomarker in the end-diastole and offer an explanation of how it obtains the result in the form of a segmentation mask without the need of segmentation labels to train the algorithm, making it a potentially more trustworthy method for clinicians and a way to train neural networks more easily when segmentation labels are not readily available.The authors acknowledge financial support from the Consel-leria d'Educacio, Investigacio, Cultura i Esport, Generalitat Valenciana (grants AEST/2019/037 and AEST/2020/029) , from the Agencia Valenciana de la Innovacion, Generalitat Valenciana (ref. INNCAD00/19/085) , and from the Centro para el Desarrollo Tecnologico Industrial (Programa Eurostars2, actuacion Interempresas Internacional) , Spanish Ministerio de Ciencia, Innovacion y Universidades (ref. CIIP-20192020) .Pérez-Pelegrí, M.; Monmeneu, JV.; López-Lereu, MP.; Pérez-Pelegrí, L.; Maceira, AM.; Bodi, V.; Moratal, D. (2021). Automatic left ventricle volume calculation with explainability through a deep learning weak-supervision methodology. Computer Methods and Programs in Biomedicine. 208:1-8. https://doi.org/10.1016/j.cmpb.2021.106275S1820

PSPU-Net for Automatic Short Axis Cine MRI Segmentation of Left and Right Ventricles

[EN] Characterization of the heart anatomy and function is mostly done with magnetic resonance image cine series. To achieve a correct characterization, the volume of the right and left ventricle need to be segmented, which is a timeconsuming task. We propose a new convolutional neural network architecture that combines U-net with PSP modules (PSPU-net) for the segmentation of left and right ventricle cavities and left ventricle myocardium in the diastolic frame of short-axis cine MRI images and compare its results against a classic 3D U-net architecture. We used a dataset containing 399 cases in total. The results showed higher quality results in both segmentation and final volume estimation for a test set of 99 cases in the case of the PSPU-net, with global dice metrics of 0.910 and median absolute relative errors in volume estimations of 0.026 and 0.039 for the left ventricle cavity and myocardium and 0.051 for the right ventricles cavity.DM acknowledges financial support from the Conselleria d'Educacio, Investigacio, Cultura i Esport, Generalitat Valenciana (grants AEST/2019/037 and AEST/2020/029), from the Agencia Valenciana de la Innovacion, Generalitat Valenciana (ref. INNCAD00/19/085), and from the Centro para el Desarrollo Tecnologico Industrial (Programa Eurostars-2, actuacion Interempresas Internacional), Spanish Ministerio de Ciencia, Innovacion y Universidades (ref. CIIP20192020). We are grateful to Andres Larroza for his valuable technical assistance in the project.Pérez-Pelegrí, M.; Monmeneu, JV.; López-Lereu, MP.; Ruiz-España, S.; Del-Canto, I.; Bodi, V.; Moratal, D. (2020). PSPU-Net for Automatic Short Axis Cine MRI Segmentation of Left and Right Ventricles. IEEE Computer Society. 1048-1053. https://doi.org/10.1109/BIBE50027.2020.00177S1048105

Role of PCSK9 in the course of ejection fraction change after ST-segment elevation myocardial infarction : a pilot study

Altres ajuts: Conselleria d'Educació, Investigació, Cultura i Esport GV/2018/116Proprotein convertase subtilisin/kexin type 9 (PCSK9) has emerged as a therapeutic target for reducing plasma low-density lipoprotein cholesterol. Beyond lipid control, recent findings suggest a deleterious effect of this protein in the pathogenesis of postmyocardial infarction left ventricle remodelling and heart failure-related complications. The aim of this study was to assess the relationship between circulating PCSK9 and 6 month cardiac magnetic resonance imaging-derived left ventricular ejection fraction (LVEF) after a first ST-segment elevation myocardial infarction (STEMI). We prospectively evaluated 40 patients with a first STEMI, LVEF < 50% and treated with primary percutaneous coronary intervention in which PCSK9 was measured 24 h postreperfusion. All patients underwent cardiac magnetic resonance imaging 1 week and 6 months after STEMI. Baseline characteristics were compared across median values of PCSK9. The association between PCSK9 levels and LVEF at 6 months was evaluated by analysis of covariance. The mean age of the sample was 60 ± 12 years and 33 (82.5%) were male patients. The infarct location was anterior in 27 patients (67.5%), and 9 patients (22.5%) were Killip class ≥ II. The mean 1 week and 6 month LVEF were 41 ± 7% and 48 ± 10%, respectively. The mean PCSK9 was 1.93 ± 0.38 U/mL. Testing the association between serum PCSK9 and 6 month LVEF with analysis of covariance revealed an inverse relationship (r = −0.35, P = 0.028). After multivariate adjustment, circulating PCSK9 remained significant and inversely associated with 6 month LVEF (P = 0.002). In patients with a first STEMI with reduced ejection fraction at index admission and treated with primary percutaneous coronary intervention, circulating PCSK9 was associated with lower LVEF at 6 months

Direct Oral Anticoagulants versus Warfarin in Octogenarians with Nonvalvular Atrial Fibrillation: A Systematic Review and Meta-Analysis

Direct oral anticoagulants (DOACs) have been demonstrated to be more effective and safer than vitamin-K antagonist (VKA) for stroke prevention in patients with nonvalvular atrial fibrillation (AF). This meta-analysis aims to assess the effect of DOACS vs. VKA in patients ≥ 80 and AF. Primary endpoints were stroke or systemic embolism and all-cause death. Secondary endpoints included major bleeding, intracranial bleeding, and gastrointestinal bleeding. A random-effects model was selected due to significant heterogeneity. A total of 147,067 patients from 16 studies were included, 71,913 (48.90%) treated with DOACs and 75,154 with VKA (51.10%). The stroke rate was significantly lower in DOACs group compared with warfarin group (Relative risk (RR): 0.72; 95% confidence interval (CI): 0.63-0.82; p < 0.001). All-cause mortality was significantly lower in DOACs group compared with warfarin group (RR: 0.82; 95% CI: 0.70-0.96; p = 0.012). Compared to warfarin, DOACs were not associated with reductions in major bleeding (RR: 0.85, 95% CI 0.69-1.04; p = 0.108) or gastrointestinal bleeding risk (RR: 1.08, 95% CI 0.76-1.53; p = 0.678) but a 43% reduction of intracranial bleeding (RR: 0.47, IC 95% 0.36-0.60; p < 0.001) was observed. Our meta-analysis demonstrates that DOACs are effective and safe with statistical superiority when compared with warfarin in octogenarians with AF

Acute Coronary Syndrome in the Older Patient

Coronary artery disease is one of the leading causes of morbidity and mortality, and its prevalence increases with age. The growing number of older patients and their differential characteristics make its management a challenge in clinical practice. The aim of this review is to summarize the state-of-the-art in diagnosis and treatment of acute coronary syndromes in this subgroup of patients. This comprises peculiarities of ST-segment elevation myocardial infarction (STEMI) management, updated evidence of non-STEMI therapeutic strategies, individualization of antiplatelet treatment (weighting ischemic and hemorrhagic risks), as well as assessment of geriatric conditions and ethical issues in decision making

Prediction of Reverse Remodeling at Cardiac MR Imaging Soon after First ST-Segment-Elevation Myocardial Infarction: Results of a Large Prospective Registry

[EN] Conclusion: Assessment of infarct size and MVO with cardiac MR imaging soon after STEMI enables one to make a decision in the prediction of reverse remodeling. (C) RSNA, 2015Supported by the Instituto de Salud Carlos III and FEDER (grant PI1400271) and the Generalitat Valenciana (grant PROMETEO/2013/007).Bodi, V.; Monmeneu, J.; Ortiz-Perez, J.; López-Lereu, M.; Bonanad, C.; Husser, O.; Minana, G.... (2016). Prediction of Reverse Remodeling at Cardiac MR Imaging Soon after First ST-Segment-Elevation Myocardial Infarction: Results of a Large Prospective Registry. Radiology. 278(1):54-63. https://doi.org/10.1148/radiol.2015142674S5463278

Coronary Revascularization and Long-Term Survivorship in Chronic Coronary Syndrome

Ischemic heart disease (IHD) persists as the leading cause of death in the Western world. In recent decades, great headway has been made in reducing mortality due to IHD, based around secondary prevention. The advent of coronary revascularization techniques, first coronary artery bypass grafting (CABG) surgery in the 1960s and then percutaneous coronary intervention (PCI) in the 1970s, has represented one of the major breakthroughs in medicine during the last century. The benefit provided by these techniques, especially PCI, has been crucial in lowering mortality rates in acute coronary syndrome (ACS). However, in the setting where IHD is most prevalent, namely chronic coronary syndrome (CCS), the increase in life expectancy provided by coronary revascularization is controversial. Over more than 40 years, several clinical trials have been carried out comparing optimal medical treatment (OMT) alone with a strategy of routine coronary revascularization on top of OMT. Beyond a certain degree of symptomatic improvement and lower incidence of minor events, routine invasive management has not demonstrated a convincing effect in terms of reducing mortality in CCS. Based on the accumulated evidence more than half a century after the first revascularization procedures were used, invasive management should be considered in those patients with uncontrolled symptoms despite OMT or high-risk features related to left ventricular function, coronary anatomy, or functional assessment, taking into account the patient expectations and preferences

A Novel Clinical and Stress Cardiac Magnetic Resonance (C-CMR-10) Score to Predict Long-Term All-Cause Mortality in Patients with Known or Suspected Chronic Coronary Syndrome

[EN] Vasodilator stress cardiac magnetic resonance (stressCMR) has shown robust diagnostic and prognostic value in patients with known or suspected chronic coronary syndrome (CCS). However, it is unknown whether integration of stressCMR with clinical variables in a simple clinical-imaging score can straightforwardly predict all-cause mortality in this population. We included 6187 patients in a large registry that underwent stressCMR for known or suspected CCS. Several clinical and stressCMR variables were collected, such as left ventricular ejection fraction (LVEF) and ischemic burden (number of segments with stress-induced perfusion defects (PD)). During a median follow-up of 5.56 years, we registered 682 (11%) all-cause deaths. The only independent predictors of all-cause mortality in multivariable analysis were age, male sex, diabetes mellitus (DM), LVEF and ischemic burden. Based on the weight of the chi-square increase at each step of the multivariable analysis, we created a simple clinical-stressCMR (C-CMR-10) score that included these variables (age >= 65 years = 3 points, LVEF 5 segments = 1 point). This 0 to 10 points C-CMR-10 score showed good performance to predict all-cause annualized mortality rate ranging from 0.29%/year (score = 0) to >4.6%/year (score >= 7). The goodness of the model and of the C-CMR-10 score was separately confirmed in 2 internal cohorts (n> 3000 each). We conclude that a novel and simple clinical-stressCMR score, which includes clinical and stressCMR variables, can provide robust prediction of the risk of long-term all-cause mortality in a population of patients with known or suspected CCS.This work was supported by the Instituto de Salud Carlos III and co-funded by Fondo Europeo de Desarrollo Regional (FEDER) (grant numbers PI17/01836 and CIBERCV16/11/00486).Marcos-Garces, V.; Gavara-Doñate, J.; Monmeneu-Menadas, JV.; Lopez-Lereu, MP.; Pérez, N.; Rios-Navarro, C.; De Dios, E.... (2020). A Novel Clinical and Stress Cardiac Magnetic Resonance (C-CMR-10) Score to Predict Long-Term All-Cause Mortality in Patients with Known or Suspected Chronic Coronary Syndrome. Journal of Clinical Medicine. 9(6):1-13. https://doi.org/10.3390/jcm9061957S11396Hendel, R. C., Friedrich, M. G., Schulz-Menger, J., Zemmrich, C., Bengel, F., Berman, D. S., … Nagel, E. (2016). CMR First-Pass Perfusion for Suspected Inducible Myocardial Ischemia. 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Left ventricular ejection fraction and presence of myocardial necrosis assessed by cardiac magnetic resonance imaging correctly risk stratify patients with stable coronary artery disease: a multi-center all-comers trial. Clinical Research in Cardiology, 106(3), 219-229. doi:10.1007/s00392-016-1042-5Catalano, O., Moro, G., Perotti, M., Frascaroli, M., Ceresa, M., Antonaci, S., … Priori, S. G. (2012). Late gadolinium enhancement by cardiovascular magnetic resonance is complementary to left ventricle ejection fraction in predicting prognosis of patients with stable coronary artery disease. Journal of Cardiovascular Magnetic Resonance, 14(1). doi:10.1186/1532-429x-14-29Lipinski, M. J., McVey, C. M., Berger, J. S., Kramer, C. M., & Salerno, M. (2013). Prognostic Value of Stress Cardiac Magnetic Resonance Imaging in Patients With Known or Suspected Coronary Artery Disease. 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