Many agents thought to attenuate reperfusion injury have been unsuccessful in clinical investigation. In this study, adenosine resulted in a significant reduction in infarct size. These data support the need for a large clinical outcome trial.

Tolvaptan coadministration does not alter steady-state amiodarone or desethylamiodarone concentrations. Tolvaptan concentrations did not appear to be different from historical controls. The most frequently reported adverse event was polyuria (15 of 21 subjects for amiodarone + 30 mg tolvaptan); an expected outcome due to the known potent aquaretic action of tolvaptan. The combination of amiodarone and tolvaptan was well tolerated.

No abstract

Maximal utility of accessible data is attractive to all partners in clinical research, whether it directly improves patient care or more accurately allows identification of the safety and efficacy of a new drug or procedure. The Food and Drug Administration (FDA) has presented a guideline draft addressing digitization of electrocardiogram (ECG) data in clinical trials to improve the standards for collection, analysis, and storage of safety information on new medical therapies. This FDA initiative has led to discussions and collaboration among the FDA, the pharmaceutical industry, the electrocardiography manufacturers, and the academic as well as the nonacademic ECG core labs. In this article, we present a broad-based viewpoint from two groups of academic ECG core labs, the Alliance of Academic ECG Core Labs and the Virtual Electronic ECG Corelab International Consortium. We have chosen to widen the perspective from using digitized ECG data in safety trials only, as addressed by the FDA guideline draft, to a discussion on the possibilities and the potential problems when using digitized ECG data also in large clinical trials focusing on efficacy measurements. We conclude that the benefit of digital data mining is probably well worth an initial incremental effort and expense.

Chronic heart failure (CHF) is associated with increased inflammation. As inflammation impairs skeletal muscle protein maintenance, elevated skeletal muscle inflammation may increase the risk of developing CHF‐associated cachexia. Elevated expression and activation of the innate immune receptor, toll‐like receptor 4 (TLR4) may contribute to skeletal muscle inflammation. The purpose of the present study was to compare skeletal muscle expression of TLR4, phosphorylated‐IκBα (a marker of TLR4 activity), and the inflammatory cytokines IL‐6 and TNF‐α between CHF patients and healthy, age‐matched controls. Biopsies were taken from the vastus lateralis of CHF patients (CHF, N=8) and healthy controls (CON, N=8), and Western blotting was used to analyze skeletal muscle TLR4, phosphorylated‐IκBα, IL‐6, and TNF‐α. Additionally, serum levels of IL‐6 and TNF‐α were measured using enzyme linked immunosorbent assays. Compared to CON, CHF exhibited elevated skeletal muscle expression of phosphorylated‐IκBα and TNF‐α. There were trends for skeletal muscle TLR4 (P=0.15), serum IL‐6 (P=0.10) and serum TNF‐α (P=0.09) to be elevated in CHF compared to CON. These preliminary data show that CHF patients exhibit greater skeletal muscle inflammation than healthy controls, and that this difference may be partially explained by elevated TLR4 signaling. Funding: P30 AG024832.

Postinfarction angina greatly increases the risk of reinfarction, especially when accompanied by transient ECG changes. However, mortality is markedly increased only in the presence of concomitant hemodynamic abnormalities.