PROJECT: Outcome Research in Advanced Heart Failure
Early publications focused on organization of multidisciplinary care and clinical outcomes in advanced heart failure, mechanical support, and heart transplantation.
Heart failure affects >6 million people in the United States. For selected patients with advanced heart failure for whom optimal medical management does not provide a good enough longevity & quality of life outlook, we consider the options of coronary artery bypass graft (CABG) surgery, percutaneous coronary interventions (PCI) (recruitment goal n=250) (Stratum #1=Ischemia), aortic valve replacement (AVR) surgery, mitral valve replacement (MVR) surgery, trans-catheter aortic valve replacement (TAVR), transcatheter Mitral Clip (Stratum #2=Overload), ventricular tachycardia ablation and stellate gangliectomy (Stratum #3=Arrhythmia), and mechanical circulatory support (MCS) surgery, heart transplantation (HTx) surgery (Stratum #4=Dyscontractility). For patients who are neither candidates for heart transplantation nor lifelong mechanical circulatory support and are very ill, based on advance care planning, less aggressive therapy focusing on quality of life and alleviation of suffering may be an alternative.
The current outcomes project focusses on retrospective validation of Functional Recovery Potential Across 7 Years of UCLA Advanced Heart Failure Patient care.
Deng, MC, Treasure, T., De Meester, J. M., Smits, J. M., Heinecke, J., Scheld, H. H., & Murday, A. (2000). Effect of receiving a heart transplant: analysis of a national cohort entered on to a waiting list, stratified by heart failure severityCommentary: Time for a controlled trial?. Bmj, 321(7260), 540-545.
Deng MC, Edwards LB, Hertz MI, Rowe AW, Keck BM, Kormos R, Naftel DC, Kirklin JK, Taylor DO. Mechanical circulatory support device database of the International Society for Heart and Lung Transplantation: third annual report—2005. The Journal of heart and lung transplantation. 2005 Sep 1;24(9):1182-7.
PROJECT: Molecular Biomarkers in Heart Transplantation
From this emerged the translational interest of the relationship between immunological activation and cardiovascular outcomes, most visibly in the completed “Immunology of Cardiac Rejection” AlloMapTM project. Over the last >20 years, working in my labs at Stanford University, Muenster University, Columbia University and UCLA, we have co-developed the first diagnostic and prognostic peripheral blood mononuclear cell (PBMC) gene expression profiling (GEP) biomarker test in transplantation medicine that gained US-FDA-regulatory clearance and international evidence-based medicine guideline acceptance to rule out rejection without invasive biopsies.
PROJECT: Molecular Biomarkers in Advanced Heart Failure
Conceptually related to the AlloMapTM project is the ongoing Advanced Heart Failure Organ Dysfunction project. Based on the AlloMapTM success, the NIH-United States Critical Illness and Injury Trials (USCIIT) Group invited us in 2008 to expand this work to develop a similar PBMC-GEP biomarker test to 1) better understand HF-related frailty and organ dysfunction, 2) better diagnose and predict outcomes, and 3) better treat HF-related organ dysfunction. We propose the overall project hypothesis that the interaction between altered leukocyte and endothelial cell biology in hypoperfused organs and tissues has the potential to worsen organ dysfunction and further activate the immune system, leading to uncontrolled systemic inflammatory response, MOD and death. We are now expanding on this work to develop a genomic blood test to better predict outcomes in patients with various forms of heart failure (MyLeukoMAPTM).
Sub-Project 1: Aging & Functional Recovery Potential In Advanced Heart Failure
Our central hypothesis is that organ dysfunction and patient death after mechanical circulatory support- or heart transplantation-surgery is resulting from innate and adaptive immune cell dysfunction reflecting an age-related reduced “Functional Recovery Potential (FRP)” that can be predicted by a multidimensional molecular biomarker (MMB) test.
Bondar G, Cadeiras M, Wisniewski N, Maque J, Chittoor J, Chang E, Bakir M, Starling C, Shahzad K, Ping P, Reed E, Deng MC. Comparison of whole blood and peripheral blood mononuclear cell gene expression for evaluation of the perioperative inflammatory response in patients with advanced heart failure. PloS one. 2014 Dec 17;9(12):e115097.
Bondar, G., Togashi, R., Cadeiras, M., Schaenman, J., Cheng, R. K., Masukawa, L., ... & Deng MC. (2017). Association between preoperative peripheral blood mononuclear cell gene expression profiles, early postoperative organ function recovery potential and long-term survival in advanced heart failure patients undergoing mechanical circulatory support. PloS one, 12(12), e0189420.
PROJECT: Systems Biology
Integrating these clinical-translational projects is the lab’s systems biological conceptual work.
Cadeiras M, von Bayern M, Sinha A, Shahzad K, Latif F, Lim WK, Grenett H, Tabak E, Klingler T, Califano A, Deng MC. Drawing networks of rejection–a systems biological approach to the identification of candidate genes in heart transplantation. Journal of cellular and molecular medicine. 2011 Apr 1;15(4):949-56.
PROJECT: Molecular Biomarkers for CMV-Infection after Transplantation
The goal of this project are to conduct systems analyses of heterologous immunity during CMV infection and define the role of CMV infection on the generation of heterologous T cell alloimmunity in renal transplantation.
PROJECT: Molecular Biomarkers in Heart Failure with Preserved Ejection Fraction
The goal of this project is to develop and combine patient-specific clinical MRI and LV pressure data in a computer model to diagnose changes in diastolic myocardial stiffness in patients with HFpEF.
PROJECT: Molecular Biomarkers in Myocarditis
PROJECT: Science In the Making
The link between our practice of modern medicine, training of humanism in medicine and research apprenticeship into the clinical framework of a humanistically sound high–tech modern medicine paradigm is reflected in our research collaboration with Prof. Federica Raia (UCLA DGSOM and GSEIS).
PROJECT: Relational Medicine
Linking systems biology back into the clinical framework of a humanistically sound high –tech modern medicine encounter is reflected in my most recent research collaboration with Prof. Federica Raia (UCLA DGSOM and GSEIS) in the “Relational Medicine” project.
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