Large-scale partial sequencing of randomly selected cDNA clones to generate expressed sequence tags (ESTs) is an efficient means of discovering novel genes and characterizing transcription in different tissues. To characterize gene expression and its changes in cardiac development and disease, an EST project was initiated using adult and fetal human heart cDNA libraries. Generation of 3,874 ESTs from an adult heart library, representing the first catalogue of genes expressed in the cardiovascular system, revealed that approximately half of all transcripts represented genes of unknown function. Analysis of the remaining half of transcripts representing known genes demonstrated expression patterns consistent with physiologic function of the heart. Comparison of these patterns with those derived from 2,244 ESTs generated from fetal heart, and with patterns obtained from other tissues, found several differences in gene expression between fetal and adult heart suggestive of a rapidly growing, less differentiated phenotype in the fetal heart relative to the adult heart. Further acquisition of larger numbers of ESTs from nine cardiac cDNA libraries, coupled with development of new strategies for data analysis, allowed for detailed prediction of individual genes exhibiting differential expression in cardiac development and disease. These strategies were applied to analyze gene expression in hypertrophic failing heart, and to study the expression of cell cycle regulators in cardiac development and hypertrophy. In the former analysis, a total of 64 genes was predicted to be differentially expressed in cardiac hypertrophy. Supporting the validity of these predictions, RT-PCR analysis of 12 of these genes confirmed 11 to be differentially expressed. In the latter analysis, transcripts of cell cycle regulators were suggested to be differentially expressed between fetal and adult hearts. Subsequent ' in vitro' analyses confirmed down-regulation of S- and G2/M-phase regulators in adult heart relative to fetal heart, and also found re-induction of several S-phase (e.g., cyclin A, PCNA), but not G2/M-phase (e.g., cyclin B, cdc2), regulators in hypertrophy. These results extend, at a molecular level, current understanding of cardiovascular function, while suggesting several new avenues of investigation. Further, they demonstrate the power of EST-based expression analyses for exploring questions of cardiovascular biology and medicine.

Ventricular arrhythmias cause most cases of sudden cardiac death, which is the leading cause of death in the US. This issue reviews the causes of arrhythmias and the promising new drugs and devices to treat arrhythmias.

Raising hopes for disease treatment and prevention, but also the specter of discrimination and "designer genes," genetic testing is potentially one of the most socially explosive developments of our time. This book presents a current assessment of this rapidly evolving field, offering principles for actions and research and recommendations on key issues in genetic testing and screening. Advantages of early genetic knowledge are balanced with issues associated with such knowledge: availability of treatment, privacy and discrimination, personal decision-making, public health objectives, cost, and more. Among the important issues covered: Quality control in genetic testing. Appropriate roles for public agencies, private health practitioners, and laboratories. Value-neutral education and counseling for persons considering testing. Use of test results in insurance, employment, and other settings.

This book delineates the state of the art of the diagnosis and treatment of J wave syndromes, as well as where future research needs to be directed. It covers basic science, translational and clinical aspects of these syndromes. The authors are leading experts in their respective fields, who have contributed prominently to the literature concerning these topics. J wave syndromes are one of the hottest topics in cardiology today. Cardiac arrhythmias associated with Brugada syndrome (BrS) or an early repolarization (ER) pattern in the inferior or infero-lateral ECG leads are thought to be mechanistically linked to accentuation of transient outward current (Ito)-mediated J waves. Although BrS and ER syndrome (ERS) differ with respect to magnitude and lead location of abnormal J waves, they are thought to represent a continuous spectrum of phenotypic expression termed J wave syndromes. ERS is divided into three subtypes with the most severe, Type 3, displaying an ER pattern globally in the inferior, lateral and right precordial leads. BrS has been linked to mutations in 19 different genes, whereas ERS has been associated with mutations in 7 different genes. There is a great deal of confusion as to how to properly diagnose and treat the J wave syndromes as well as confusion about the underlying mechanisms. The demonstration of successful epicardial ablation of BrS has provided new therapeutic options for the management of this syndrome for which treatment alternatives are currently very limited, particularly in the case of electrical storms caused by otherwise uncontrollable recurrent VT/VF. An early repolarization pattern is observed in 2-5% of the US population. While it is clear that the vast majority of individuals exhibiting an ER pattern are not at risk for sudden cardiac death, the challenge moving forward is to identify those individuals who truly are at risk and to design safe and effective treatments.