Heart failure remains a leading cause of morbidity and mortality worldwide. Although depressed pump function is common, development of effective therapies to stimulate contraction has proven difficult. This is thought to be attributable to their frequent reliance on cAMP stimulation to increase activator Ca ²⁺ . A potential alternative is nitroxyl (HNO), the 1-electron reduction product of nitric oxide (NO) that improves contraction and relaxation in normal and failing hearts in vivo. The mechanism for myocyte effects remains unknown. Here, we show that this activity results from a direct interaction of HNO with the sarcoplasmic reticulum Ca ²⁺ pump and the ryanodine receptor 2, leading to increased Ca ²⁺ uptake and release from the sarcoplasmic reticulum. HNO increases the open probability of isolated ryanodine-sensitive Ca ²⁺ -release channels and accelerates Ca ²⁺ reuptake into isolated sarcoplasmic reticulum by stimulating ATP-dependent Ca ²⁺ transport. Contraction improves with no net rise in diastolic calcium. These changes are not induced by NO, are fully reversible by addition of reducing agents (redox sensitive), and independent of both cAMP/protein kinase A and cGMP/protein kinase G signaling. Rather, the data support HNO/thiolate interactions that enhance the activity of intracellular Ca ²⁺ cycling proteins. These findings suggest HNO donors are attractive candidates for the pharmacological treatment of heart failure.

Objective: To examine evidence‐based quality indicators (QIs) in US veterans with gout diagnosis, and to examine the effect of demographics, heath care utilization/access, comorbid conditions, or physican characteristics as predictors of quality of gout care.Methods: Using the Minneapolis Veterans Affairs electronic medical record system, we identified a cohort of veterans receiving medication to treat gout between January 1, 1999 and December 31, 2003, and evaluated 3 recently published evidence‐based QIs for gout management: QI 1 = allopurinol dose <300 mg in gout patients with renal insufficiency, QI 2 = uric acid check within 6 months of starting a new allopurinol prescription, and QI 3 = complete blood count and creatine kinase check every 6 months for gout patients receiving prolonged colchicine therapy. We calculated the proportion of patients whose therapy adhered to each QI and to all applicable indicators (overall physician adherence). Logistic regression analysis examined association of overall physician adherence with sociodemographics, health care utilization, comorbidity, and provider characteristics.Results: Of 3,658 patients with a diagnosis of gout, 663 patients qualified for examination of ≥1 QI. Of these 663 patients, therapy in only 144 (22%) adhered to all applicable QIs; 59 (78%) of 76 adhered to QI 1, 155 (24%) of 643 adhered to QI 2, and 18 (35%) of 52 adhered to QI 3. Overall physician adherence to QIs was significantly lower in older veterans and in those with more inpatient visits per year, but was higher in those with more primary care visits or more health care providers.Conclusion: Suboptimal physician adherence to QIs was seen for all 3 QIs tested in this cohort of veterans with gout. These findings can guide quality improvement efforts.