Actividade de Investigação

INVESTIGATION GROUPS

A. | Ischemia models, myocardial regeneration and cardiac intervention (Fausto J. Pinto)

Ischemia model. The need to develop a therapeutic agent to prevent or attenuate IRI is generally recognized. No such agents are currently approved for clinical use. We aim to develop more accurate pre-clinical models of IRI in rodents as well as human plasma samples to further translate our results for the human setting. Ultimately the improvements we are expecting to obtain in organ function will translate into clinical use and the request in EU and FDA for the designation as Orphan Medicinal Product of the drugs and hence allow the development with advice of the regulatory agencies of a drug for this clinical situation for which no therapeutic options are available. The proposed strategies took into consideration the research published by our group but in short term we propose to study the effect of recombinant human erythropoietin and the analogue ARA290 and the inhibition of GSK3beta (two highly specific inhibitors available to our groups). In general, the purposes of the experiments to be conducted in this project are to identify the effect of different pharmacological interventions in the prevention/treatment of the organ injury/dysfunction associated to septic shock. Serum and urinary indicators of organ injury/dysfunction will be measured, as well as relevant organ sections for histologic scoring of organ injury and for immunologic evidence of nitrotyrosine formation and poly [ (ADP)-ribose] (PAR). Nitrate levels measured in rat plasma using the Griess assay. Citokyne levels, namely IL-1ß, IL-6 nad TNFalpha will be also examined. Organ myeloperoxidase (MPO) activity and malondialdehyde (MDA) levels will be measured using state of the art molecular biology technology available.

Incremental value of myocardial oxygenation by CMR on high-resolution perfusion for ischemia detection. Main objectives of this study is assessing the incremental diagnostic accuracy of BOLD CMR at 3.0 T in patients with suspected coronary artery disease in addition to high-resolution stress-perfusion, using coronary angiography with invasive fractional flow reserve (FFR) determination as the reference method for ischemia. Secondary objectives: a) to compare the accuracy of two different BOLD protocols for myocardial ischemia as classified by FFR; b) To compare the BOLD findings with the perfusion severity and coronary anatomic severity; c) to analyze the clinical significance of BOLD and perfusion findings in the long-term prognosis of patients not submitted to intervention, based on the FFR findings.

Left atrial appendage closure in atrial fibrillation in TAVI. Promote a multicenter study in patients programmed to receive TAVI for aortic stenosis and concomitant atrial fibrillation with high stroke risk (CHA2DS2-VASC score = 2) and high bleeding risk (HAS-BLED = 3). Patients will be randomized (1:1) to TAVI plus percutaneous LAA closure or TAVI alone. Both groups will be treated with double antiplatelet therapy for 6 months followed by monotherapy. The primary composite end-points will be efficacy (stroke; systemic embolization and cardiovascular/unexplained death) and safety (cardiac tamponade; major bleeding; procedure-related stroke; hemorrhagic stroke; device embolization) at 2 and 5-years follow-up. We aim to evaluate efficacy and safety of LAA closure in valvular (TAVI) atrial fibrillation with high bleeding risk.

Myocardial regeneration: The strategic program will be implemented through an integrative partnership of CCUL and other research Units such as the IMM (Institute of Molecular Medicine), the Genetics and the Physiology Department of the Faculty of Medicine of Lisbon University. The Catheterization Laboratory, the Magnetic Resonance unit are directly integrated in the Unit through the CCUL researchers, which are either responsible for those Units or for the research activity related to these projects. Partnerships are also being established with international Centres[AA1] , such as Brigham & Women’s Hospital. 

 

B. | Heart failure and cardiomyopathies (Dulce Brito)

This Research Group has developed research activity on two pillars Heart failure and Cardiomyopathies and is formed by recognized experienced cardiologists (3 PhD), full members of the CCUL and several co-investigators (described in team section), including a one clinical geneticist and one molecular geneticist.

All of the researchers are directly or indirectly linked to the Faculty of Medicine and Santa Maria University Hospital. The RG uses the facilities provided by the Department of Cardiology at Santa Maria University Hospital to which all members have an open access and where most of them work permanently on a daily basis. The group will be coordinated by Dulce Brito the PI. The scientific part of the project will be conducted by the PI and Prof. Hugo Madeira. The group will take regular meetings with the whole team (every 2 months) in order to discuss the work done so far, solve potential problems and proceed to any adjustment needed.

The Department of Cardiology is equipped with all modern non-invasive techniques, essentials in terms of diagnosis, functional and organic evaluation, risk assessment and treatment monitoring. The group has outstanding achievements regarding scientific publications and participation in both national and international scientific meetings.

 

C. | Hypertension neurovascular control and target organs dysfunction (J. Braz Nogueira)

The group has been investigating the evolution of hypertensive disease, and injuries to major organs affected by this disease, namely kidney, arteries, eye, central nervous system and heart.

 

D. | Research Group on Vascular Biology, Imaging and Surgery (J. Fernandes e Fernandes)

The group developped the following areas of investigation:
- Identification of active carotid lesions using high definition ultrasonography with computer-assisted plaque analysis.
- 3D Assessment of carotid plaques based on ultrasonographic images.
- Biochemical and echo-structural determinats of athersoclerotic plaque vulnerability.
- Repercussion of chronic inflammation on the endothelial function and its influence in early atherosclerosis development in systemic rheumatic diseases

 

E. | Valvular Heart Disease and Pulmonary Hypertension. From biomarkers to fluid mechanics and cell biology (Ana G. Almeida).

This Research Group has developed research activity on two pillars, pulmonary hypertension and valvular heart disease. Pulmonary artery hypertension is a condition associated with high mortality, in any of the clinical presentations and etiologies and represents a heavy economical burden for the costly therapies now available. On the other hand, there is a lack of knowledge on the mechanisms, clinical outcome is variable and a need to assess and understand the effect and mechanisms of newer therapies on morbidity and mortality. We have been developing studies to better understand the underlying pathophysiology, using cutting-edge basic science (such as genetic assessment and novel physiologic biomarkers), pulmonary vessel wall dynamics, as well as heart structure and function, using advanced imaging (echocardiography, cardiovascular magnetic resonance and computed tomography). New therapeutic agents are being tested and monitored regarding the clinical effects and the changes on hemodynamics, biomarkers and cardiovascular function. The physiologic response to exercise and pharmacological stress has also been a matter of research, since we hypothesise that this may have impact in prognosis.

Valvular heart disease (VHD) has been the other pillar of research of this group, which only in the next project will be structured in the CCUL. VHD interacts with pulmonary artery hypertension, adding an unfavourable impact on the outcome. The underlying mechanisms for development of pulmonary artery hypertension in patients with VHD are not clearly established and are being investigated by our group, using both basic science, biomarkers and advanced cardiovascular imaging. Additionally and importantly, the research on valvular disease itself is focused on understanding the changes of valve structure, cell biology and fluid and pressure dynamics, assess the impact on cardiovascular function and histopathology structure using advanced imaging methods (two-dimensional and three-dimensional echocardiography, cardiovascular magnetic resonance, strain imaging, cardiac CT), bio-imaging and biomarkers. The impact of genetics on the severity and prognosis is also being tested. New methods for valve pathophysiology evaluation and cardiovascular function are being developed by a team of clinical, basic and physics scientists, and compared with the conventional methods. An important area of study is focused on the prognosis of valve heart disease patients with new therapies, pharmacological and devices implantation, directed to reduce adverse events and improve outcome and long-term survival. Another future area regards the role of VHD in myocardial diseases due to systemic conditions. This program has been started during the previous years but is now ready to follow a more comprehensive path in the next 2014-2020 in order to better understand and study the disease mechanisms and to assess and monitor the impact on prognosis, namely using new diagnostic techniques and tests. The clinical effect and its mechanisms of action of new therapies will be thoroughly investigated and we expect with our research to improve the survival and the morbidity of these patients.

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