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- Perspectives on directions and priorities for future preclinical studies in regenerative medicinePublication . Grigorian Shamagian, Lilian; Madonna, Rosalinda; Taylor, Doris; Climent, Andreu M.; Prosper, Felipe; Rosario, Luis; Bayes-Genis, Antoni; Ferdinandy, Péter; Fernández-Avilés, Francisco; Izpisua Belmonte, Juan Carlos; Fuster, Valentin; Bolli, RobertoThe myocardium consists of numerous cell types embedded in organized layers of ECM (extracellular matrix) and requires an intricate network of blood and lymphatic vessels and nerves to provide nutrients and electrical coupling to the cells. Although much of the focus has been on cardiomyocytes, these cells make up <40% of cells within a healthy adult heart. Therefore, repairing or regenerating cardiac tissue by merely reconstituting cardiomyocytes is a simplistic and ineffective approach. In fact, when an injury occurs, cardiac tissue organization is disrupted at the level of the cells, the tissue architecture, and the coordinated interaction among the cells. Thus, reconstitution of a functional tissue must reestablish electrical and mechanical communication between cardiomyocytes and restore their surrounding environment. It is also essential to restore distinctive myocardial features, such as vascular patency and pump function. In this article, we review the current status, challenges, and future priorities in cardiac regenerative or reparative medicine. In the first part, we provide an overview of our current understanding of heart repair and comment on the main contributors and mechanisms involved in innate regeneration. A brief section is dedicated to the novel concept of rejuvenation or regeneration, which we think may impact future development in the field. The last section describes regenerative therapies, where the most advanced and disruptive strategies used for myocardial repair are discussed. Our recommendations for priority areas in studies of cardiac regeneration or repair are summarized in Tables 1 and 2 .
- Omalizumab induced Takotsubo syndrome : case reportPublication . Aguiar-Ricardo, Inês; Nunes-Ferreira, Afonso; Roda, Ângela; Rosario, LuisBackground: Omalizumab is a humanized monoclonal anti-immunoglobulin E antibody, approved for the treatment of spontaneous chronic urticaria, with high efficacy and an excellent safety profile. Although its adverse effects are rare, allergic reactions and cardiovascular events were previously described. Case summary: The authors describe the case of a 75-year-old woman, followed at the outpatient dermatology clinic due to spontaneous chronic urticaria, treated with omalizumab 300 mg every 4 weeks. After the 11th administration of omalizumab, the patient developed an episode of thoracalgia associated with electro- and echocardiographic abnormalities. Coronary angiogram excluded coronary artery disease, and left ventriculography demonstrated mid-apical akinesia and basal hyperkinesia, consistent with the Takotsubo syndrome (TS). Discussion: Takotsubo syndrome was already reported in association with other monoclonal antibodies. However, to our knowledge, this is the first case of TS following the administration of omalizumab.
- Secondary mitral valve regurgitation dynamic response during isometric exercisePublication . de Sousa, Teresa Reynolds; André, Nzinga; Almeida, Ana G.; Pinto, Fausto J.; Rosario, LuisObjective: Secondary Mitral Valve Regurgitation (SMVR) is a dynamic condition whose severity is modified by different loading conditions, and prior studies found increases in regurgitation under stress conditions to convey higher morbidity and mortality. Therapeutic options in SMVR include pharmacologic therapy, percutaneous device or repair surgery, and recent guidelines acknowledge gaps in evidence for specific subsets of patients. Stress echocardiography identifies the dynamic modifications during altered loading conditions and may become a helpful tool in managing this condition. Isometric stress increases arterial blood pressure with minor changes in heart rate. In this study, we aim to identify the acute changes in SMVR during isometric exercise in order to develop a diagnostic and prognostic test.
- e-CoVig: a novel mHealth system for remote monitoring of symptoms in COVID-19Publication . Raposo, Afonso; Marques, Luis; Correia, Rafael; Melo, Francisco; Valente, João; Pereira, Telmo; Rosario, Luis; Froes, Filipe; Sanches, João; Silva, Hugo Plácido daIn 2019, a new virus, SARS-CoV-2, responsible for the COVID-19 disease, was discovered. Asymptomatic and mildly symptomatic patients were forced to quarantine and closely monitor their symptoms and vital signs, most of the time at home. This paper describes e-CoVig, a novel mHealth application, developed as an alternative to the current monitoring paradigm, where the patients are followed up by direct phone contact. The e-CoVig provides a set of functionalities for remote reporting of symptoms, vital signs, and other clinical information to the health services taking care of these patients. The application is designed to register and transmit the heart rate, blood oxygen saturation (SpO2), body temperature, respiration, and cough. The system features a mobile application, a web/cloud platform, and a low-cost specific device to acquire the temperature and SpO2. The architecture of the system is flexible and can be configured for different operation conditions. Current commercial devices, such as oximeters and thermometers, can also be used and read using the optical character recognition (OCR) functionality of the system. The data acquired at the mobile application are sent automatically to the web/cloud application and made available in real-time to the medical staff, enabling the follow-up of several users simultaneously without the need for time consuming phone call interactions. The system was already tested for its feasibility and a preliminary deployment was performed on a nursing home showing promising results.
- Left ventricular systolic dysfunction in Marfan syndrome is related to aortic distensibilityPublication . Rigueira, Joana; Placido, R.; David, Cláudio; Rosario, Luis; Aguiar-Ricardo, Inês; Campos, P.; Francisco, Ana Rita; Pinto, Fausto J.; G. Almeida, AnaBackground: The cardiovascular involvement in Marfan syndrome (MS) is characterized mainly by dilatation and reduced distensibility of the ascending aorta. Left ventricular (LV) dysfunction has been detected in MS and a primary cardiomyopathy has been suggested but the pathophysiology is unclear. The purpose of this study was to evaluate the LV function in patients with MS and to assess the relationship with the aortic distensibility, as possible underlying mechanism. Methods: We studied 53 patients with MS (27.0 ± 11 years, 29 men) without valvular or hypertensive heart disease and a control group of 26 healthy subjects (29 ± 9 years, 17 men). All underwent echocardiography and cardiac magnetic resonance (CMR) and the following indexes were analyzed: a) Echo: mitral flow velocities E/A ratio and deceleration of mitral E; E’ velocity obtained from the medial and lateral mitral ring; E/E’ ratio b) CMR: LV volumes indexed to BSA and ejection fraction (EF); global longitudinal strain (GLS, Circle cvI42); maximal size and distensibility of proximal ascending aorta. Distensibility was calculated from maximal (systolic) and minimum (diastolic) area of maximal proximal ascending aorta (cross-sectional images from SSFP sequence) using the formula=(maximum area-minimum area)/[ minimum area x (systolic BP-diastolic BP)]. Results: 17 from 53 patients with MS had increased LV end-diastolic volume, 14 decreased EF (<50%) and 22 decreased GLS. Compared with the control group, patients with MS showed increased LV end-diastolic volume (85.0 ± 5.2vs 80.1 ± 5.3ml/m2, p = 0.04), lower GLS (17.1 ± 1.9 vs 18.9 ± 2.2, p = 0.01) lower LVEF (53.0 ± 7.1% vs 56.0 ± 5.4%, p = 0.03) and higher E/E’ value (9.2 ± 1.3 vs. 6.2 ± 0.8, p = 0.01) as well as larger dimensions of proximal aorta (39 ± 2.2cm vs 32 ± 0.8,p = 0.010) and lower aortic distensibility (3.4 ± 1.9 vs. 4.4 ± 1.7 dynes cm-1, p = 0.03). In the group of patients, a correlation was found between the aortic distensibility and the LVEF (r = 0.47, p = 0.045) and GLS (r = 0.65, p = 0.02), but not with the other variables. Aortic distensibility was an independent predictor of LV dysfunction using a cutoff of 50% for LVEF and 19% for GLS. Conclusion: In our population of patients with MS, we found changes in the LV function, which were related with aortic distensibility, possibly sharing a common pathway. The prognostic significance of these findings is under evaluation.
- Ventricular tachycardia revealing cardiac infiltration by mycosis fungoidesPublication . Carrilho-Ferreira, Pedro; Ferreira, Marco; Ferreira, Cristina; Correia, Maria José; Nunes Diogo, António; Rosario, LuisA 53-year-old man, with a 15-year history of mycosis fungoides (MF), presented with fever, dizziness, and presyncope. On examination, he was tachycardic (180 bpm) and hypotensive (100/70 mmHg). The ECG showed diffuse ST-segment depression, and cardiac troponin I was elevated (3.47 ng/ml). He was admitted with a suspected acute coronary syndrome. On the third day of hospitalization there were several episodes of sustained monomorphic ventricular tachycardia (MVT).
- AI-driven decision support for early detection of cardiac events: unveiling patterns and predicting myocardial ischemiaPublication . Elvas, Luís B.; Nunes, Miguel; Ferreira, Joao C.; Dias, Miguel Sales; Rosario, LuisCardiovascular diseases (CVDs) account for a significant portion of global mortality, emphasizing the need for effective strategies. This study focuses on myocardial infarction, pulmonary thromboembolism, and aortic stenosis, aiming to empower medical practitioners with tools for informed decision making and timely interventions. Drawing from data at Hospital Santa Maria, our approach combines exploratory data analysis (EDA) and predictive machine learning (ML) models, guided by the Cross-Industry Standard Process for Data Mining (CRISP-DM) methodology. EDA reveals intricate patterns and relationships specific to cardiovascular diseases. ML models achieve accuracies above 80%, providing a 13 min window to predict myocardial ischemia incidents and intervene proactively. This paper presents a Proof of Concept for real-time data and predictive capabilities in enhancing medical strategies.