Human Cardiac-Specific cDNA Array for Idiopathic Dilated Cardiomyopathy: Sex-Related Differences

Idiopathic dilated cardiomyopathy (IDCM) constitutes a large portion of patients with heart failure of unknown etiology. Up to 50% of all transplant recipients carry this clinical diagnosis. Female-specific gene expression in IDCM has not been explored. We report sex-related differences in the gene expression profile of ventricular myocardium from patients undergoing cardiac transplantation. We produced and sequenced subtractive cDNA libraries, using human left ventricular myocardium obtained from male transplant recipients with IDCM and nonfailing human heart donors. With the resulting sequence data, we generated a custom human heart failure microarray for IDCM containing 1,145 cardiac-specific oligonucleotide probes. This array was used to characterize RNA samples from female IDCM transplant recipients. We identified a female gene expression pattern that consists of 37 upregulated genes and 18 downregulated genes associated with IDCM. Upon functional analysis of the gene expression pattern, deregulated genes unique to female IDCM were those that are involved in energy metabolism and regulation of transcription and translation. For male patients we found deregulation of genes related to muscular contraction. These data suggest that 1) the gene expression pattern we have detected for IDCM may be specific for this disease and 2) there is a sex-specific profile to IDCM. Our observations further suggest for the first time ever novel targets for treatment of IDCM in women and men

Nuggets, Pearls, and Vignettes of Master Heart Failure Clinicians

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/73696/1/j.1527-5299.2001.00307.x.pd

758–3 Right Ventricular Ejection Fraction is an Independent Predictor of Maximum Oxygen Consumption in Advanced Heart Failure

Maximum oxygen consumption (MVO2), left ventricular ejection fraction (LVEF), and left ventricular end-diastolic volume index (LVEDVI) are important determinants of prognosis in heart failure (HF). To determine the ventriculographic parameters influencing MVO2, simultaneous cardiopulmonary exercise testing (cycle ergometry) and first-pass rest and exercise radionuclide ventriculography were performed in 66 patients with advanced HF (age 51±9.9 mean±SD, NYHA 3±0.6, LVEF 0.22±0.07, RVEF 0.29±0.11, LVEDVI 154±49 m1/M2) during initial cardiac transplant evaluation. Mean percent predicted age-sex adjusted MVO2 achieved (%MVO2) was 38±12%. Univariate predictors of %MVO2 included RVEF at rest (p=0.001). RVEF at peak exercise (p=0.001), %maximum heart rate achieved (%MHR, p<0.01), LVESVI (p<0.05). and NYHA (p=0.05). Resting HR, resting or peak systolic or diastolic blood pressure, resting or peak exercise LVEF, exercise-related rise or fall>0.05 in either LVEF or RVEF, rest or peak exercise cardiac index, rest or peak exercise LVEDVI, NYHA, and diagnosis were not significant univariate predictors of %MVO2. RVEF at rest (p=0.001) and %MHR (p=(0.01) were the only independent predictors in a multiple linear regression model.ConclusionsIn patients with advanced HF, 1) RVEF is an independent predictor of %MVO2 and 2) neither rest or exercise LVEF predicts %MVO2