Istaroxime: A New Luso-Inotropic Agent for Heart Failure

Istaroxime: Is the Remedy Better than the Disease?

“…In the same study, istaroxime was also administered for the first time, orally for 34 weeks, to cardiomyopathic Syrian BIO TO.2 hamsters. The drug prolonged survival to 32% of the animals [15]. The same investigators have also shown previously that istaroxime was more effective than dobutamine in improving left ventricular performance in the early (2-3 days) and late (2 weeks) phase of acute myocardial infarction in a canine model [18].…”

“…It is known that sympathetic activation plays a crucial pathogenetic role in the development and progression of heart failure and markers of its function, such as heart rate variability, represent independent predictors of patients' outcome. According to the analysis of heart rate variability, istaroxime prevented the disturbance of autonomic tone by preserving the parasympathetic activity [19], expanding previous reports showing that istaroxime did not affect heart rate [15,16]. In addition, an improvement of coronary flow reserve was also documented [19].…”

“…Micheletti et al showed that intravenous istaroxime improved several echocardiographic contraction and relaxation indices in guinea pigs that had been exposed to 3-month aortic banding [17]. In another study by Mattera et al, a 24-hour intravenous istaroxime infusion at 1, 3, and 4 μg/kg/min to dogs increased left ventricular dP/dtmax and -dP/dtmax, without changing heart rate, blood pressure, or double product or causing arrhythmic events [15]. In the same study, istaroxime was also administered for the first time, orally for 34 weeks, to cardiomyopathic Syrian BIO TO.2 hamsters.…”

“…The novel agent istaroxime seems to respond to both of the above abnormalities by its dual mechanism of action that includes inhibition of the sodium-potassium ATPase and stimulation of the sarcoplasmic reticulum calcium ATPase (SERCA) isoform 2 (SERCA2). The first property induces cytoplasmic calcium accumulation with a positive inotropic response, while the second one leads to rapid clearance of cytoplasmic calcium to sarcoplasmic reticulum, leading to myocardial relaxation and a lucitropic response and at the same time preventing arrythmiogenesis caused by calcium overload [15]. Thus, istaroxime acts as an intracellular calcium modulator, in favor of the contraction-relaxation cycle [14].…”

SERCA2a: its role in the development of heart failure and as a potential therapeutic target

“…38,39 Due to its double action, istaroxime has been proved to treat acute HF syndrome in guinea pigs and dogs, improving systolic and diastolic function, central hemodynamics, systolic blood pressure, and reducing heart rate. [40][41][42] Istaroxime has also been used in human patients; the Hemodynamic, Echocardiographic, and Neurohor- …”