Junior Recital:Michelle Kittleson, Flute

Kemp Recital Hall Wednesday Evening April 18, 2007 7:00p.m

GENE EXPRESSION PROFILING IN ISCHEMIC AND NONISCHEMIC CARDIOMYOPATHY

Background Despite our growing understanding of the pathophysiology and management of heart failure, there exist no strategies to individualize therapy using predictors of long-term prognosis and response to therapy. Gene expression analysis using microarray technology provides a phenotypic resolution not possible with standard clinical criteria and could offer insights into disease mechanisms and also identify markers useful for diagnostic, prognostic, and therapeutic purposes. Thus, the two major applications of this technology are gene discovery and molecular signature analysis. These two applications were explored in studies involving the two major forms of cardiomyopathy, ischemic and nonischemic (ICM and NICM, respectively). Methods For a gene discovery analysis, we compared the gene expression of 21 NICM and 10 ICM samples with that of 6 nonfailing (NF) hearts using Affymetrix U133A microarrays and Significance Analysis of Microarrays software. For molecular signature analysis, we identified and validated an etiology signature with Prediction Analysis of Microarrays software using 48 ICM and NICM myocardial samples obtained from different institutions and at different clinical stages. Results The gene discovery analysis demonstrated that compared to NF hearts, 257 genes were differentially expressed in NICM and 72 genes in ICM. Only 41 genes were shared between the two comparisons and an analysis of the gene subsets revealed shared and unique disease-specific gene expression between end-stage cardiomyopathy of different etiologies. The molecular signature analysis demonstrated that an etiology prediction profile accurately distinguished between ICM and NICM, was generalizable to iii samples from separate institutions, specific to disease stage, and unaffected by differences in clinical characteristics. Conclusions We have demonstrated that there are shared and distinct genes involved in the development of heart failure of different etiologies, and that a molecular signature can accurately identify etiology in cardiomyopathy. These findings highlight the utility of the two distinct applications of gene expression analysis, and support ongoing efforts to develop cause-specific therapies and expression profiling-based biomarkers in heart failure. The ultimate goal is individualized therapy, whereby a heart failure patient could, through gene expression analysis, be offered an accurate assessment of prognosis, and how individualized medical therapy could affect his or her outcome

Implications of Extra-cardiac Disease in Patient Selection for Heart Transplantation: Considerations in Cardiac Amyloidosis

Disease-modifying therapies in both light chain and transthyretin amyloidosis have improved patient functional status and survival. Conceivably, as heart failure may progress despite amyloid therapies, more patients may be considered for heart transplantation. In earlier eras, extra-cardiac amyloid deposits significantly reduced post-heart transplant patient survival and functional status compared to the non-amyloid population. In the modern era, transplant centres have reported improved outcomes in amyloidosis as patient selection has grown more stringent. Importantly, systematic candidate evaluation should assess the degree of extra-cardiac involvement, the effectiveness of disease-modifying therapies and downstream effects on patients’ nutrition and frailty. This review outlines such an overall approach while also considering that organ-specific selection criteria may vary between individual transplant centres. A methodical approach to patient evaluation will promote better understanding of the prevalence and severity of extra-cardiac disease in amyloidosis patients referred for heart transplantation and of any disparities in decision outcomes in this population

Effects of Older Donor Age and Cold Ischemic Time on Long-Term Outcomes of Heart Transplantation

Using older donor hearts in cardiac transplantation may lead to inferior outcomes: older donors have more comorbidities that reduce graft quality, including coronary artery disease, hypertension, diabetes mellitus, and dyslipidemia. Shorter cold ischemic times might overcome the detrimental effect of older donor age. We examined the relationship between donor allograft age and cold ischemic time on the long-term outcomes of heart transplant recipients. rom 1994 through 2010, surgeons at our hospital performed 745 heart transplantations. We retrospectively classified these cases by donor ages of(younger) and ≥50 years (older), then by cold ischemic times of(short), 120 to 240 min (intermediate), and \u3e240 min (long). Endpoints included recipient and graft survival, and freedom from cardiac allograft vasculopathy, nonfatal major adverse cardiac events, and rejection. For intermediate ischemic times, the 5-year recipient survival rate was lower when donors were older (70% vs 82.6%

Characteristics, Outcomes, and Predictors of De Novo Malignancy After Heart Transplantation

BACKGROUND: Post-transplant malignancy (PTM) causes long-term morbidity and mortality in heart transplant (HTx) recipients. However, the detailed characteristics or predictors of PTM are not well-known. We evaluated the incidence, characteristics, long-term outcomes, and predictors of METHODS: We retrospectively analyzed the types and characteristics of RESULTS: Two hundred and six patients (20.8%) had CONCLUSION: Older age, white race, and longer administration of immunosuppressive therapies were independent risk factors for PTM, which was associated with increased mortality. Further research is necessary for the prevention and early detection of PTM in HTx recipients

2017 ACC/AHA/HFSA/ISHLT/ACP Advanced Training Statement on Advanced Heart Failure and Transplant Cardiology (Revision of the ACCF/AHA/ACP/HFSA/ISHLT 2010 Clinical Competence Statement on Management of Patients With Advanced Heart Failure and Cardiac Transplant)

Since the 1995 publication of its Core Cardiovascular Training Statement (COCATS),1 the American College of Cardiology (ACC) has played a central role in defining the knowledge, experiences, skills, and behaviors expected of all clinical cardiologists upon completion of training. Subsequent updates have incorporated major advances and revisions—both in content and structure—including, most recently,

Recent advances in heart transplantation [version 1; referees: 2 approved]

Despite advances in medical and electrical therapies for heart failure, morbidity and mortality remain high and patients often progress to end-stage heart failure. Over the last five decades, heart transplantation is considered a standard therapy for select patients with end-stage heart failure. However, while heart transplantation has become a treatment of choice for end-stage heart failure, challenges still exist for improvement in the short- and long-term outcomes. While there is an increase in the number of patients with end-stage heart failure, the number of donor organs remains a major limiting factor. Heart transplantation candidates in the current era are also more complex: older, antigen-sensitized, and on mechanical circulatory support at the time of listing and transplant. Such potential heart transplant recipients have an increased chance of problems, including antibody-mediated rejection and primary graft dysfunction. Recent advances could address the current challenges and include: 1) attempts to expand the pool of donor hearts; 2) changes in heart transplantation allocation policy allowing for more equitable organ distribution; and 3) advances in the management of antibody sensitization. Developments in these areas could result in improved survival and quality of life for heart transplantation recipients