Treatment with 24 hour istaroxime infusion in patients hospitalised for acute heart failure: a randomised, placebo‐controlled trial

Abstract

Istaroxime is a first-in-class agent which acts through inhibition of the sarcolemmal Na + /K + pump and activation of the SERCA2a pump. This study assessed the effects of a 24 h infusion of istaroxime in patients hospitalised for acute heart failure (AHF).

Istaroxime in acute heart failure: the holy grail is at HORIZON?

“…19 In the present study, there were no differences in troponin release after study drug infusion in either the istaroxime or placebo group. 16 These findings suggest that istaroxime-induced improvements in diastolic function do not increase myocardial oxygen demand or increase myocardial damage. Along with improvement in renal function (increased eGFR), these effects suggest better organ protection, making the drug a potentially attractive option for the treatment of patients with hypotension and low cardiac output (Figure 1).…”

“…Potential role of istaroxime in the management of patients with acute heart failure (AHF). The HORIZON-HF 13 and Istaroxime ADHF 16 clinical trials have shown improvement of diastolic properties, without increasing heart rate or decreasing systolic blood pressure (SBP). CS, cardiogenic shock; IV, intravenous.…”

“…12 A favourable lusitropic effect, as assessed by increased mitral deceleration time, occurred only at the highest dose. 15 In this issue of the Journal, Carubelli et al 16 evaluated the effects of a 24 h infusion of two doses of istaroxime in patients hospitalized for AHF with left ventricular ejection fraction (LVEF) ≤40%. The study was a randomized, double-blind, placebo-controlled, parallel-group study, designed to evaluate the efficacy of two different doses of istaroxime (0. at rest or on minimal exertion and need for intravenous diuretic therapy (>40 mg intravenous furosemide); SBP between 90 and 125 mmHg without signs or symptoms of peripheral hypoperfusion; intermediate to high E/e ′ ratio by tissue Doppler echocardiography (>10); B-type natriuretic peptide (BNP) or N-terminal pro-BNP (NT-proBNP) plasma levels ≥350 pg/mL or ≥1400 pg/mL, respectively.…”

Cardiac foetal reprogramming: a tool to exploit novel treatment targets for the failing heart

“…Treatment with istaroxime in animal models of HF have shown improved cardiac function with no adverse effects [121,122]. Following these animal studies, a clinical trial evaluating the effects of acute istaroxime administration in HF patients has demonstrated an improvement in cardiac function in these patients [123][124][125]. Although such a pharmacological intervention does not directly target cardiac foetal reprogramming, like direct gene therapy does, it does ensure that the remaining SERCA2 is more active, therefore compensating for the lack of SERCA2 expression.…”

September 2020 at a glance: focus on heart failure with preserved ejection fraction and medical therapy

“…19 In patients hospitalized for acute HF, istaroxime had beneficial effects on left ventricular function, without hypotension, tachycardia, or serious cardiac adverse events. 20…”