Safety and efficacy of istaroxime in patients with acute heart failure‐related pre‐cardiogenic shock – a multicentre, randomized, double‐blind, placebo‐controlled, parallel group study (<scp>SEISMiC</scp>)

Metra, Marco; Chioncel, Ovidiu; Cotter, Gad; Davison, Beth A.; Filippatos, Gerasimos; Mebazaa, Alexandre; Novosadova, Maria; Ponikowski, Piotr; Simmons, Phillip; Soffer, Joseph; Simonson, Steven G.

doi:10.1002/ejhf.2629

Cited by 19 publications

(20 citation statements)

References 14 publications

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“…The 24 h infusion has shown beneficial changes in echocardiography parameters, with a lack of major cardiac adverse effects in the acute HF patients’ cohort. These results are in line with the recent study by Metra et al, where the inotropic effect of istaroxime increased cardiac index with blood pressure changes and reduced left ventricular and atrial dimensions [ 193 ]. Interestingly, istaroxime shows less cardiotoxic and arrhythmogenic properties alongside significant inotropic effects than classical inotropes [ 194 ].…”

Section: Combination Of Mechanical Unloading and Pharmacotherapy For ...supporting

confidence: 93%

Novel Targets for a Combination of Mechanical Unloading with Pharmacotherapy in Advanced Heart Failure

Jędrzejewska

Braczko

Kawecka

et al. 2022

IJMS

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LVAD therapy is an effective rescue in acute and especially chronic cardiac failure. In several scenarios, it provides a platform for regeneration and sustained myocardial recovery. While unloading seems to be a key element, pharmacotherapy may provide powerful tools to enhance effective cardiac regeneration. The synergy between LVAD support and medical agents may ensure satisfying outcomes on cardiomyocyte recovery followed by improved quality and quantity of patient life. This review summarizes the previous and contemporary strategies for combining LVAD with pharmacotherapy and proposes new therapeutic targets. Regulation of metabolic pathways, enhancing mitochondrial biogenesis and function, immunomodulating treatment, and stem-cell therapies represent therapeutic areas that require further experimental and clinical studies on their effectiveness in combination with mechanical unloading.

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Section: Combination Of Mechanical Unloading and Pharmacotherapy For ...supporting

confidence: 93%

Novel Targets for a Combination of Mechanical Unloading with Pharmacotherapy in Advanced Heart Failure

Jędrzejewska

Braczko

Kawecka

et al. 2022

IJMS

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“…cardiac index, LA area, and LV end-systolic volume) and was well tolerated. 364 Procalcitonin-guided initiation of antibiotic therapy did not improve clinical outcomes compared with standard of care in 742 patients admitted for acute HF. 365…”

Section: Treatmentmentioning

confidence: 94%

“…The Phase 2a SEISMIC study, including patients with pre‐CS, istaroxime improved BP and echocardiography measures related to HF (i.e. cardiac index, LA area, and LV end‐systolic volume) and was well tolerated 364 …”

Section: Acute Heart Failurementioning

confidence: 99%

Heart failure: an update from the last years and a look at the near future

et al. 2022

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In the last years, major progress occurred in heart failure (HF) management. Quadruple therapy is now mandatory for all the patients with HF with reduced ejection fraction. Whilst verciguat is becoming available across several countries, omecamtiv mecarbil is waiting to be released for clinical use. Concurrent use of potassium-lowering agents may counteract hyperkalaemia and facilitate renin-angiotensin-aldosterone system inhibitor implementations. The results of the EMPagliflozin outcomE tRial in Patients With chrOnic heaRt Failure With Preserved Ejection Fraction (EMPEROR-Preserved) trial were confirmed by the Dapagliflozin in Heart Failure with Mildly Reduced or Preserved Ejection Fraction (DELIVER) trial, and we now have, for the first time, evidence for treatment of also patients with HF with preserved ejection fraction. In a pre-specified meta-analysis of major randomized controlled trials, sodium-glucose co-transporter-2 inhibitors reduced all-cause mortality, cardiovascular (CV) mortality, and HF hospitalization in the patients with HF regardless of left ventricular ejection fraction. Other steps forward have occurred in the treatment of decompensated HF. Acetazolamide in Acute Decompensated Heart Failure with Volume Overload (ADVOR) trial showed that the addition of intravenous acetazolamide to loop diuretics leads to greater decongestion vs. placebo. The addition of hydrochlorothiazide to loop diuretics was evaluated in the CLOROTIC trial. Torasemide did not change outcomes, compared with furosemide, in TRANSFORM-HF. Ferric derisomaltose had an effect on the primary outcome of CV mortality or HF rehospitalizations in IRONMAN (rate ratio 0.82; 95% confidence interval 0.66-1.02; P = 0.070). Further options for the treatment of HF, including device therapies, cardiac contractility modulation, and percutaneous treatment of valvulopathies, are summarized in this article.

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“…Istaroxime has improved diastolic and systolic cardiac function among patients hospitalized for acute HFrEF 33 . The phase 2a SEISMiC trial randomized 60 patients with acute HF with pre‐cardiogenic shock, defined as systolic blood pressure <90 mmHg without hypoperfusion, venous lactate ≥2 mmol/L and/or mechanical or inotropic support, to istaroxime 1.0–1.5 μg/kg/min or placebo for 24 h. Istaroxime improved systolic blood pressure without significant differences in serious adverse events or adverse events except for more nausea, vomiting and infusion site pain in the istaroxime‐treated patients 34 …”

Section: Acute Heart Failurementioning

confidence: 99%

“…33 μg/kg/min or placebo for 24 h. Istaroxime improved systolic blood pressure without significant differences in serious adverse events or adverse events except for more nausea, vomiting and infusion site pain in the istaroxime-treated patients. 34 Early assessment of urinary sodium (UNa) concentration can be useful to assess intrinsic renal sodium avidity (IRSA). 35 Patients with a random UNa spot sample before randomization from the ROSE-AHF trial were categorized according to tertiles of UNa as high (range 19-40 mmol/L), intermediate (range 41-68 mmol/L), or low (range 69-139 mmol/L) IRSA.…”

Section: Acute Heart Failurementioning

confidence: 99%

October 2022 at a glance: focus on clinical trials

Tomasoni

Adamo

Metra

2022

European J of Heart Fail

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Assessment of biomarkers is a cornerstone of heart failure (HF) management. [1][2][3][4] A review from the Biomarkers Working Group of the Heart Failure Association summarizes the utility of biomarkers for defining and managing congestion on top of clinical evaluation, haemodynamics, and imaging. 5 The same group also reviewed the use of circulating biomarkers in clinical trials. They may be used as inclusion criteria, as surrogate endpoints, or as safety endpoints. 6 Focus on clinical trials SGLT2 inhibitorsSodium-glucose cotransporter 2 (SGLT2) inhibitors are recommended as foundational therapy for patients with HF and reduced ejection fraction (HFrEF) for their effects on mortality and HF hospitalizations. [7][8][9][10] They also improved quality of life in randomized controlled trials but their effects on exercise capacity, a measurement not changed by neurohormonal modulators, are less studied. 11 In the multicentre randomized double-blind DAPA-VO 2 trial, dapagliflozin, compared with placebo, significantly improved peak oxygen consumption at 1 and 3 months in stable patients with HFrEF. 12 Administration of SGLT2 inhibitors is associated with an initial decline in estimated glomerular filtration rate (eGFR). Changes in eGFR from randomization to week 4 were assessed in the EMPEROR-Reduced trial. On average, empagliflozin induced a leftward shift of the distribution of the initial eGFR changes, i.e. a greater decrease, of -2.5 ml/min/1.73 m 2 versus placebo in patients with HFrEF. 13 The initial mild decline in eGFR was not associated with a higher risk of HF, mortality, or kidney safety events. 13 Similarly, in the EMPULSE trial, including patients hospitalized for acute HF with an eGFR >20 ml/min/1.73 m 2 , empagliflozin caused an initial decline in eGFR of -2 ml/min/1.73 m 2 at day 15 compared to placebo that was no longer evident at day 90. The clinical benefit of empagliflozin was independent of baseline eGFR. 14 Liver dysfunction is a marker of more severe HF and an independent predictor of poor prognosis. 15 In the Dapagliflozin And Prevention of Adverse outcomes in Heart Failure (DAPA-HF) trial, patients with the highest bilirubin tertile had more severe HFrEF

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Safety and efficacy of istaroxime in patients with acute heart failure‐related pre‐cardiogenic shock – a multicentre, randomized, double‐blind, placebo‐controlled, parallel group study (SEISMiC)

Cited by 19 publications

References 14 publications

Novel Targets for a Combination of Mechanical Unloading with Pharmacotherapy in Advanced Heart Failure

Novel Targets for a Combination of Mechanical Unloading with Pharmacotherapy in Advanced Heart Failure

Heart failure: an update from the last years and a look at the near future

October 2022 at a glance: focus on clinical trials

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