Showing 4 ideas for tag "ischemic"

Goal 3: Advance Translational Research

New Targets for the Treatment of Heart Failure

Heart failure (HF) is one of the major health challenges in the 21st Century. Its prevalence is due a growing number of patients who survive heart attacks, who later develop heart failure; and the high incidence of diabetes leading to diabetic cardiomyopathy. Current treatments for HF only slow the progression of the disease; no treatment stops or reverses this adverse sequence. These limitations provoke the question... more »

Is this idea a Compelling Question (CQ) or Critical Challenge (CC)? Compelling Question (CQ)

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The current treatment regimens for patients with heart failure (HF) focus on strategies to reduce cardiac work (by reducing heart rate, beta-blockers), afterload reduction (ACE inhibitors), and decrease in preload/blood volume (ACE inhibitors, aldosterone antagonists, diuretics). None of these treatments stop or reverse the progression of the disease. A recent gene therapy trial designed to improve cardiac contractility and calcium handling in HF has failed in clinical trials. Perhaps the reason that the current and experimental treatments have not produced an outcome of stopping or reversing the progression of the disease relates to the "cell" they are targeting. In this regard, the current treatments principally target cardiac myocytes, but there is evidence that vascular perfusion abnormalities may also be involved in the disease. One such piece of evidence relates to the diffuse fibrosis occurring in the failing hearts. Such fibrosis is often referred to as replacement fibrosis in that the fibrotic tissue has replaced cardiac myocytes which died. This death could be the result of a perfusion abnormalities caused by inadequate dilation of the coronary resistance vessels. Thus, is heart failure a pathology involving both the coronary circulation and cardiac muscle? In this regard, future investigations of heart failure consider cardiac-coronary interactions leading to perfusion abnormalities as a key factor in the progression of heart failure.

Feasibility and challenges of addressing this CQ or CC

The challenge of addressing a coronary vascular contribution to heart failure would involve an interdisciplinary approach using genetic models with cardiac and/or vascular (smooth muscle and endothelium) expression or knock-out of key genes involved in cardiac function and vascular control. Sophisticated measurements of cardiac function and metabolic status of the heart using echocardiography, MRI, PET and a L-Band EPR would provide insight into flow-function-metabolism-oxygenation relations in the normal and failing heart.

Name of idea submitter and other team members who worked on this idea William M Chilian

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Goal 2: Reduce Human Disease

Noninvasive biomarkers for characterizing cardiovascular disease

Critical Challenge

Is this idea a Compelling Question (CQ) or Critical Challenge (CC)? Critical Challenge (CC)

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Phenotypical characterization of cardiovascular disease with computed tomography (CT) and magnetic resonance imaging (MR) to individualize targeted therapies for coronary artery and myocardial disease. Coronary artery disease is a major cause of patient death in the United States. Nonischemic myocardial disease includes entities with clinically heterogeneous presentations and is thus challenging to manage.

Feasibility and challenges of addressing this CQ or CC

Currently CT and MR technology allows dynamic evaluation of the perfusion and contractility of the heart. Quantitative measures of disease burden, such as atherosclerotic plaque composition and myocardial texture imaging biomarkers (such as T1 mapping, activation mapping, flow pattern analysis, delayed myocardial enhancement), are possible. Positron emission tomography (PET)/MR, which combines metabolic with functional evaluation, is currently available and facilitates the development of targeted molecular-imaging techniques. Metrics derived from these techniques may serve to stratify patients noninvasively and direct appropriate therapies. Such imaging methods address noninvasive evaluation of cardiovascular disease, including ischemic heart disease but also myocardial diseases that include secondary and infiltrative cardiomyopathies, hypertrophic cardiomyopathy, and organ rejection in the scenario of transplantation.

Name of idea submitter and other team members who worked on this idea Society of Thoracic Radiology

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Goal 2: Reduce Human Disease

What is the optimal management of coronary artery disease in patients with chronic kidney disease

Patients with chronic kidney disease (CKD) have an extremely high risk of death from cardiovascular cause. The prognosis of patients with chronic kidney disease who also have coronary artery disease is worse than certain cancer. While great strides have been made to create awareness about breast cancer, there is paucity of knowledge about the cardiovascular risk of CKD patients among both physicians and patients. Moreover,... more »

Is this idea a Compelling Question (CQ) or Critical Challenge (CC)? Compelling Question (CQ)

Details on the impact of addressing this CQ or CC

Patients with chronic kidney disease tend to be undertreated (from CV perspective), underrepresented (in clinical trials) and underdiagnosed with less referral for stress testing, even though cardiovascular cause is the leading cause of death in these patients. Patients with chronic kidney disease is a growing cohort and with increase in obesity and diabetes, the prevalence is exploding exponentially. The decision as to what is the best treatment option for patients with coronary artery disease who also have kidney disease- revascularization or medical therapy-is important and can be a paradigm shift in the way we treat such patients

Feasibility and challenges of addressing this CQ or CC

Randomized clinical trials are urgently needed to answer this question.

Name of idea submitter and other team members who worked on this idea Sripal Bangalore

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Goal 2: Reduce Human Disease

Identify Pathways of Risk Linking Psychosocial Stress to Ischemic Heart Disease in Women

Women differ from men in their manifestations of ischemic heart disease (IHD). They also differ from men with respect to prevalence of psychosocial factors and vulnerability to specific mental disorders. Young women, in particular, appear to be highly susceptible to the adverse cardiovascular effects of psychosocial stress. Those who already have clinical manifestations of IHD display high psychosocial burden which could... more »

Is this idea a Compelling Question (CQ) or Critical Challenge (CC)? Compelling Question (CQ)

Details on the impact of addressing this CQ or CC

The study of young women from the community, and women with early-onset IHD, could be critical in uncovering women-specific pathways of IHD risk related to psychosocial stress. Investigations of the association between psychosocial factors and IHD should include sufficient numbers of young and middle-aged adults, and rather than only adjusting for sex, should conduct analyses stratified by sex. If psychosocial stress is a major risk factor for early-onset IHD in women, then psychosocial interventions specifically tailored to address women’s stressors and applied early in women’s lives should be especially helpful in improving or reverting IHD risk in this group. Most psychosocial or drug treatment interventions for depression have not been effective for improving IHD outcomes particularly among women, suggesting that more attention should be given to psychosocial pathways specific for women and to the identification of vulnerable subsets.

Feasibility and challenges of addressing this CQ or CC

Calls for proposals for mechanistic studies and intervention trials targeted to young women and men at risk for IHD or sampled according to different exposure levels should be a feasible starting point to investigate this area and begin identifying vulnerable subgroups and sex differences.

Name of idea submitter and other team members who worked on this idea Viola Vaccarino

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