Although neurohumoral antagonism has successfully reduced heart failure morbidity and mortality, the residual disability and death rate remains unacceptably high. Though abnormalities of myocardial metabolism are associated with heart failure, recent data suggest that heart failure may itself promote metabolic changes such as insulin resistance, in part through neurohumoral activation. A detrimental self-perpetuating cycle (heart failure --> altered metabolism --> heart failure) that promotes the progression of heart failure may thus be postulated. Accordingly, we review the cellular mechanisms and pathophysiology of altered metabolism and insulin resistance in heart failure. It is hypothesized that the ensuing detrimental myocardial energetic perturbations result from neurohumoral activation, increased adverse free fatty acid metabolism, decreased protective glucose metabolism, and in some cases insulin resistance. The result is depletion of myocardial ATP, phosphocreatine, and creatine kinase with decreased efficiency of mechanical work. On the basis of the mechanisms outlined, appropriate therapies to mitigate aberrant metabolism include intense neurohumoral antagonism, limitation of diuretics, correction of hypokalemia, exercise, and diet. We also discuss more novel mechanistic-based therapies to ameliorate metabolism and insulin resistance in heart failure. For example, metabolic modulators may optimize myocardial substrate utilization to improve cardiac function and exercise performance beyond standard care. The ultimate success of metabolic-based therapy will be manifest by its capacity further to lessen the residual mortality in heart failure.

Prescribed and supervised resistance training (RT) enhances muscular strength and endurance, functional capacity and independence, and quality of life while reducing disability in persons with and without cardiovascular disease. These benefits have made RT an accepted component of programs for health and fitness. The American Heart Association recommendations describing the rationale for participation in and considerations for prescribing RT were published in 2000. This update provides current information regarding the (1) health benefits of RT, (2) impact of RT on the cardiovascular system structure and function, (3) role of RT in modifying cardiovascular disease risk factors, (4) benefits in selected populations, (5) process of medical evaluation for participation in RT, and (6) prescriptive methods. The purpose of this update is to provide clinicians with recommendations to facilitate the use of this valuable modality.

Accelerated cardiovascular disease is a frequent complication of renal disease. Chronic kidney disease promotes hypertension and dyslipidemia, which in turn can contribute to the progression of renal failure. Furthermore, diabetic nephropathy is the leading cause of renal failure in developed countries. Together, hypertension, dyslipidemia, and diabetes are major risk factors for the development of endothelial dysfunction and progression of atherosclerosis. Inflammatory mediators are often elevated and the renin-angiotensin system is frequently activated in chronic kidney disease, which likely contributes through enhanced production of reactive oxygen species to the accelerated atherosclerosis observed in chronic kidney disease. Promoters of calcification are increased and inhibitors of calcification are reduced, which favors metastatic vascular calcification, an important participant in vascular injury associated with end-stage renal disease. Accelerated atherosclerosis will then lead to increased prevalence of coronary artery disease, heart failure, stroke, and peripheral arterial disease. Consequently, subjects with chronic renal failure are exposed to increased morbidity and mortality as a result of cardiovascular events. Prevention and treatment of cardiovascular disease are major considerations in the management of individuals with chronic kidney disease.

Whether elevated serum troponin levels identify patients with acute pulmonary embolism at high risk of short-term mortality or adverse outcome is undefined.

Diabetes mellitus increases the risk of heart failure independently of underlying coronary artery disease, and many believe that diabetes leads to cardiomyopathy. The underlying pathogenesis is partially understood. Several factors may contribute to the development of cardiac dysfunction in the absence of coronary artery disease in diabetes mellitus. This review discusses the latest findings in diabetic humans and in animal models and reviews emerging new mechanisms that may be involved in the development and progression of cardiac dysfunction in diabetes.

Since the 1980s, antifibrinolytic therapies have assisted surgical teams in reducing the amount of blood loss. To date, however, serious questions remain regarding the safety and effectiveness of these agents.

The intent of this review is to provide the clinician with a summary of what is currently known about the contribution of genetics to the origin of congenital heart disease. Techniques are discussed to evaluate children with heart disease for genetic alterations. Many of these techniques are now available on a clinical basis. Information on the genetic and clinical evaluation of children with cardiac disease is presented, and several tables have been constructed to aid the clinician in the assessment of children with different types of heart disease. Genetic algorithms for cardiac defects have been constructed and are available in an appendix. It is anticipated that this summary will update a wide range of medical personnel, including pediatric cardiologists and pediatricians, adult cardiologists, internists, obstetricians, nurses, and thoracic surgeons, about the genetic aspects of congenital heart disease and will encourage an interdisciplinary approach to the child and adult with congenital heart disease.