Showing 3 ideas for tag "cardiomyopathy"

Goal 3: Advance Translational Research

Immunologic predictors of cardiac function following apheresis for dilated cardiomyopathy

Apheresis has been used to treat dilated cardiomyopathy yet the mechanism of action and predictors of response are unknown and clinical utility needs to be confirmed. What is the clinical utility, mechanism of action, and predictors of response?

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

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Dilated cardiomyopathy (DCM) is progressive ventricular enlargement and dysfunction, responsible for 10,000 deaths and 46,000 hospitalizations in the U.S. annually. It is the primary indication for heart transplantation. It may represent viral infection triggered autoimmunity with myocardial autoantibodies identified in 80% of patients and higher autoimmune disease prevalence in patients.

Immunoadsorption and plasma exchange have been used to treat DCM. Staphylococcal protein A agarose (SPAA) columns have the largest published evidence with improved left ventricular (LV)ejection fraction, decreased LV circumference, decreased BNP, improved exercise tolerance, improved oxygen uptake, increased regulator T-cells, decreased stimulatory T-cells, decreased costimulatory T-cells, and improved quality of life. Decreased morbidity and mortality with fewer patients progressing to transplantation and lower health care costs has been described. Given organ shortages, morbidity, and expense of transplantation, a treatment that delays or avoids transplantation would improve health and reduced costs.

Immunological variables such as IgG subtypes, Th1, Th2, Th17 and T regulatory cell number, associated cytokines, and nuclear transcription factors implicated in DCM pathogenesis could correlate with LV function following apheresis and identify apheresis selection criteria and offer a novel mechanism to investigate how autoantibody reduction influences cellular immune components.

Feasibility and challenges of addressing this CQ or CC

DCM is the most common cause of cardiac transplantation with a large number of patients available for study. There are numerous standardized tools for measuring patient quality of life and function for those suffering from congestive heart failure. There are readily available assays for examining potential immunologic variables. If TPE is examined, this procedure is readily available.

Challenges would include the fact that the immunoadsorption columns that have been used are not cleared by the Food and Drug Administration and therefore there is limited to no experience with their use in the U.S. Immunologic evaluations could also require endomyocardial biopsy which represents an invasive procedure which could limit patient enrollment and increase risk.

Name of idea submitter and other team members who worked on this idea Bruce Saichais on behalf of ASFA

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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)

Details on the impact of addressing this CQ or CC

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

Research priorities in Pediatric Cardiomyopathy and Heart Failure

If NHLBI set research priorities for pediatric cardiomyopathy and heart failure, it would help investigators better align their application with institute goals.

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

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The most promising areas are genotype-deep phenotype studies, advances in cardiac imaging to quantify extracellular volume as a measure of fibrosis; working with industry to develop better VADS/pre-transplant devices for small children, QOL studies in heart transplant children and their families, personalized medicine, pharmacogenomics, RCTs for new heart failure interventions and also cardiac rehabilitation, leverage and expand registries to support RCTs, molecular mechanism studies including studies of restrictive physiology, using genomic findings to directly inform clinical practice.

Name of idea submitter and other team members who worked on this idea Jwilkins1953

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