Mechanism of action of the new anti-ischemia drug ranolazine

Myocardial ischemia is associated with reduced ATP fluxes and decreased energy supply resulting in disturbances of intracellular ion homeostasis in cardiac myocytes. In the recent years, increased persistent (late) sodium current was suggested to contribute to disturbed ion homeostasis by elevating intracellular sodium concentration with subsequent elevation of intracellular calcium. The new anti-ischemia drug ranolazine, a specific inhibitor of late sodium current, reduces sodium overload and hence ameliorates disturbed ion homeostasis. This is associated with symptomatic improvement of angina in patients. Moreover, ranolazine was shown to exhibit anti-arrhythmic effects. In the present article, we review the relevant pathophysiological concepts for the role of late sodium inhibition and summarize the most recent data from basic as well as clinical studies

ESC guidelines for the diagnosis and treatment of acute and chronic heart failure 2012: The Task Force for the Diagnosis and Treatment of Acute and Chronic Heart Failure 2012 of the European Society of Cardiology. Developed in collaboration with the Heart Failure Association (HFA) of the ESC.

Linea guida per la pratica clinic

Seniority of the first-treating doctor does not influence the outcome of acute whiplash injury: a prospective cohort study

The aim of the prospective cohort study was to investigate the outcome of acute whiplash injury first treated either by junior doctors (JD) [≤3 postgraduate years (PGY)] or more experienced doctors (MED) (>3 PGY). At baseline, crash-related data and health parameters including the SF36 were evaluated in whiplash patients (WP), who fulfilled criteria for whiplash-associated disorders grade I–II and presented up to 48 h after motor vehicle accident to our Emergency Department. 81 WP were recruited and treated by either one of 14 JD (35 WP) or one of 22 MED (46 WP). The follow-up examination included the course of pain intensity [numeric rating scale (NRS) 0–10] by the use of a 28 days-pain-diary and the incidence of symptoms (standardized-telephone-interview at 1, 3, and 6 months post trauma) in terms of neck pain NRS > 2, analgesic medication, work-off, and utilization of further medical services as well as SF36 evaluated at the end of the study. Although the entry population seemed similar, all outcome parameters were comparable between the JD- and MED-group (p > 0.05). Therefore, we conclude that seniority of the first-treating physician does not influence the outcome of acute whiplash injury

Heart failure with preserved ejection fraction

Heart failure with preserved ejection fraction (HFpEF) is the clinical syndrome of heart failure (HF) in the presence of a normal or near-normal left ventricular (LV) systolic function. Some studies suggest that HFpEF may now be the predominant HF phenotype. It is associated with considerable morbidity and mortality, and outcomes have not improved over recent decades. The diagnosis of HFpEF can be challenging, and there is inconsistency and debate regarding which diagnostic criteria should be used. Various pathophysiological mechanisms have been implicated in the development of HFpEF; however, there is unlikely to be a single unifying paradigm. Instead, it is a condition characterised by a complex interplay of various cardiovascular mechanisms and associated comorbidities, with marked phenotypic variation between patients. To date, randomised controlled trials (RCTs) have failed to demonstrate a prognostic benefit, but several large trials of promising therapies with hard clinical endpoints are due to report soon. Future RCTs are likely to focus on assessing targeted therapies in sub-phenotypes of HFpEF