Aliskiren in the prevention of diffuse myocardial fibrosis in patients with Diabetes and hypertension with T1 mapping by 3.0T cardiovascular magnetic resonance

• Grant number: 12/17167-2
• Support Opportunities: Regular Research Grants
• Start date: March 01, 2013
• End date: February 29, 2016
• Field of knowledge: Health Sciences - Medicine - Medical Radiology
• Principal Investigator: Juliano de Lara Fernandes
• Grantee: Juliano de Lara Fernandes
• Host Institution: Faculdade de Ciências Médicas (FCM). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil

Abstract

Patients with diabetes and hypertension represent a group with high risk of cardiovascular diseases and show rapid development of cardiomyopathies. In these patients, besides coronary artery disease, increase in myocyte necrosis and diffuse interstitial fibrosis is also present. These changes occur very early in the course of the disease and already increase the patient's risks although their clinical manifestations are usually present only at later phases.The pathophysiological mechanisms that drive these changes are complex but the renin-angiotensin system plays a central role in the process. More importantly, not only the systemic stimuli are significant but also the intracellular synthesis of angiotensin II by the myocytes themselves seems to represent an essential step in the formation of interstitial fibrosis. Traditional blockers of the renin-angiotensin system using angiotensin converting enzyme inhibitors or angiotensin receptor blockers show a restricted role in the process as the intracellular mechanisms involved continue to stay ongoing despite peripheral and extra-cellular blockade.To quantitatively assess the diffuse myocardial fibrosis previously described, only recently have specific cardiovascular magnetic resonance techniques been developed. Through these techniques based on myocardial T1 mapping, it is now possible to diagnose these changes early on and to monitor the development or regression of diffuse fibrosis using magnetic resonance imaging.Based on the explained above, we propose this study to evaluate diffuse myocardial fibrosis in patients with diabetes and hypertension using T1 mapping in 3.0T magnetic resonance imaging and comparing these values to normal controls. We also propose to study the efficacy of the drug aliskiren - a direct renin inhibitor which showed to experimentally reduce the synthesis of intracellular angiotensin II by myocytes - after one year of treatment in comparison to a similar group without the use of the drug. Finally, we also want to assess whether patients who chronically and prolonged use the drug aliskiren have lower degrees of fibrosis compared to matched diabetic and hypertensive patients who have never used the drug. (AU)