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Biomedical subjects

Valentín Fuster

Publications and source records attributed to Valentín Fuster.

6 recordsLinked to original sources
PubMed2006

[Inoperable valve disease: should percutaneous valve replacement be an option?].

Surgical valve replacement is the treatment of choice in patients with severe valvular heart disease. However, published data clearly show that long-term survival is seriously compromised in those with a low inotropic reserve. In addition, a growing number of patients (estimated to be around 15% of those with aortic stenosis) present in such a poor and deteriorating clinical condition that they cannot be accepted for surgery because it involves a very high risk of death. Percutaneous balloon valvuloplasty is a less aggressive alternative which offers a form of palliative treatment that can increase the patient's life expectancy and bring about immediate hemodynamic and clinical improvement. It is in this context that the possibility of carrying out percutaneous valve replacement has become available as a novel therapeutic option since Cribier first reported using the procedure to treat a patient with severe aortic stenosis. Since this first operation, both the techniques employed and the material composition of the prosthesis have undergone substantial development. However, significant problems have been encountered in evaluating the safety and efficacy of percutaneous valve replacement. These, to a great extent, stem from the risks associated with treating elderly patients who have high morbidity and mortality. In the United States, one clinical study was even suspended because two of the first four patients undergoing treatment died. In contrast, studies carried out in other countries, although they have involved only a few patients, have produced more promising results. Moreover, because the cause of death in these series was frequently due to factors that were independent of good valvular function, the future of the technique is generally thought to be positive. Nevertheless, the results obtained with percutaneous mitral valve replacement have been poor. In conclusion, the technique of percutaneous valve replacement, although still undergoing development, is becoming established as a viable alternative for treating inoperable valve disease, at least in aortic valves.

Aortic Valve Stenosis↗
PubMed2004

[Oral antithrombins and the future of antithrombotic therapy].

The coagulation cascade leads, via thrombin activation, to the formation of fibrin (from its precursor fibrinogen) and platelet thrombus. Several drugs are able to interfere with some of the enzymatic factors involved in thrombin activation, but thrombin inhibitors (heparin, hirudin and hirulog [bivalirudin]) are of particular interest because they disrupt the coagulation cascade by acting upon one of its final steps. Among the thrombin inhibitors, oral antithrombins (ximelagatran) appear to hold great promise for the control of thrombogenicity in a number of clinical contexts. Oral antithrombins do not require the participation of cofactors to exert their action, and in contrast to thrombin inhibitors administered parenterally, they bind specifically to the active site of thrombin without interfering with other portions of the molecule. Their specificity makes these drugs safe and obviates the need to monitor coagulability. Moreover, they show a low rate of interaction with other drugs or with foods, and the response to fixed doses is predictable. A number of clinical studies have investigated antithrombins for prophylaxis prior to orthopedic surgery, in the prevention of cerebrovascular accidents associated with atrial fibrillation, and in the control of coronary artery disease. These studies have shown that antithrombins are superior to other habitually used treatment options. Surprisingly, their use in long-term studies has not been associated with an increased rate of bleeding events. Their interesting molecular characteristics and considerable therapeutic efficacy and safety suggest that oral antithrombins will in the near future become a valuable therapeutic option.

Administration, Oral↗
PubMed2003

[Role of coronary risk factors in blood thrombogenicity and acute coronary syndromes].

Recent advances in basic science have linked some systemic risk factors to endothelial dysfunction which gives rise to atherosclerotic disease and triggers the progression of thrombotic complications. Superficial erosion of the stenotic plaque can be observed in one-third of acute coronary syndromes (ACS). In these cases the presence of classic risk factors such as diabetes mellitus, hypercholesterolemia and smoking favor a state of "vulnerable blood" or high risk. Increased thrombogenicity can exacerbate thrombus formation and is able to trigger an ACS. The vessel endothelium regulates contractile, mitogenic and thrombotic activities of the vessel wall. Risk factors impair both homeostasis and hemostasis of the vessel wall and promote inflammatory signals. Platelet and monocyte activation favors the expression of tissue factor (TF), thus triggering the coagulation cascade with thrombin generation and clot formation. Increased blood thrombogenicity linked to classic risk factors may be associated with circulating TF levels which are much higher than those observed in healthy subjects without risk factors. These observations not only emphasize the usefulness of aggressive management of risk factors but open a new avenue for future studies to devise therapeutic strategies to treat ACS by inhibiting TF expression.

Acute Disease↗
PubMed2003

[Rapamycin: from the laboratory to the treatment of patients' arteries].

The history of rapamycin dates from 1965, when it was isolated from a microorganism in soil and its antibiotic properties were confirmed. Since its discovery, many scientific papers have demonstrated its antifungal and immunosuppressive properties. Our team pioneered in the study of the mechanism of action of rapamycin, motivated by its enormous promise as a therapeutic agent in atherosclerotic disease. We reported how it can inhibit the proliferation and migration of smooth muscle cells after a mechanical aggression, and demonstrated that this effect is mediated by p27 activation by rapamycin. The participation of p27, a key cyclin in the modulation of cell replication, in rapamycin's molecular signaling also spurred expectations in the field of oncological research because it involves a non-redundant system of regulation of the cell cycle susceptible to mutatio. The interesting characteristics of this active principle suggested that it would be worthwhile to investigate its protective effect in an experimental porcine model of angioplasty. Rapamycin showed that it can notably reduce vascular wall thickening, thus helping to preserve patency after angioplasty. Shortly after this study, the use of rapamycin-coated stents designed to release the active principle into the area of the atherosclerotic lesion was accompanied by an effective preservation of the arterial lumen in experimental models. It also produced a highly significant reduction in the rate of post-stent restenosis in various clinical studies in humans. However, the potential of this type of stent in diabetic patients is still unknown and we are on the point of beginning a large clinical trial (the FREEDOM study) to investigate its impact on the management of diabetic patients. Experimental and clinical evidence indicates that the development of oral agents capable of modifying the progression of atherosclerotic disease by acting on molecular targets involved in the control of the cell cycle will be a challenge in the coming years.

Animals↗
PubMed2002

[Applied cardiological research. Challenges for the new millenium].

Poor eating habits, a sedentary life style, and smoking have made acute coronary syndrome a disease characteristic of modern life. Although the widespread appearance of coronary heart disease has been delayed by 10 years, it is expected to be the primary cause of death in the world by the year 2020, in spite of the development of reperfusion therapy and the use of defibrillators. The incidence of coronary heart disease is spreading to more depressed areas and affecting an increasingly larger number of persons over 70, who are generally poorly represented in clinical studies and respond less favorably to treatment. Detaining the advance of this epidemic demands the development of a competitive research policy that includes rigorous training of researchers and scientific programs based on cooperation and teamwork. The success of this scientific strategy rests on public and private fund-raising to finance the anticipated priority areas of cardiovascular research in the coming years: vascular immunobiology, genome studies, tissue transplantation, and organogenesis. Advances in research complemented by the implementation of preventive measures based on a unified scientific approach and community educational campaigns could act effectively against the spread of cardiovascular disease in the world, thus avoiding otherwise inevitable social and economic consequences.

Biomedical Research↗