ABSTRACT
Purpose of the Review: Iron deficiency in heart failure has been associated with impaired functional capacity and quality of life. The purpose of this paper is to review mechanisms of iron homeostasis and current clinical data exploring mechanisms of iron repletion in heart failure. Recent Finding: Multiple international societies now advise iron repletion for symptomatic heart failure patients with iron deficiency. Due to the chronic inflammation in heart failure, iron deficiency in heart failure is classically defined as ferritin < 100 µg/L or ferritin 100-300 µg/L and transferrin saturation < 20%. Multiple randomized clinical trials have demonstrated benefit from intravenous iron repletion, though studies have predominantly focused on functional capacity and quality of life. A recent study, AFFIRM-AHF, supports the treatment of iron deficiency identified during acute heart failure admissions, noting a reduction in future heart failure hospitalizations. Studies examining iron repletion in patients with heart failure with preserved ejection fraction are currently in process. Summary: Iron homeostasis is maintained predominantly through the regulation of iron absorption, keeping iron levels tightly controlled in the normal state regardless of iron intake. In chronic heart failure however, iron homeostasis becomes dysregulated with resulting iron deficiency in many patients, with and without associated anemia. Iron is a critical element not only for erythropoiesis and oxygen carrying, but also for energy production at the level of the mitochondria and in other cell processes. We thus propose a standardized approach be utilized to screen and treat heart failure patients with iron deficiency.
ABSTRACT
Ranolazine is an anti-anginal medication that reduces the sodium-dependent calcium overload via the inhibition of the late sodium current. After its approval for the treatment of chronic angina in 2006 in the USA, ranolazine has been reported to have several pleiotropic effects on various cardiac conditions, such as atrial fibrillation, ventricular arrhythmias, diastolic and microvascular dysfunction, and pulmonary arterial hypertension. Recently, several studies reported some promising results on the potential benefits of ranolazine on glycemic control. Though the mechanism of the antihyperglycemic effect is still unknown, ranolazine may exert the effect through ß cell preservation, inhibition of glucose secretion, and enhancement of insulin secretion in a glucose-dependent manner. Given the increased risk of cardiovascular disease in patients with diabetes, it will be useful if one medication can simultaneously improve chronic angina and diabetes. Therefore, ranolazine could be a favored choice among other anti-anginal agents for patients with comorbidity of chronic angina and diabetes mellitus. In this review, we summarize the available data from clinical studies and provide valuable insight into defining the target population for the antihyperglycemic effect of ranolazine.
