Istaroxime, a first in class new chemical entity exhibiting SERCA-2 activation and Na-K-ATPase inhibition: a new promising treatment for acute heart failure syndromes?

Abstract:

:Acute heart failure syndromes (AHFS) are associated with the rapid onset of heart failure (HF) signs and symptoms. Hospitalizations for AHFS continue to rise and are associated with significant mortality and morbidity. Several pharmacological agents are currently approved for the treatment of AHFS, but their use is associated with an increase in short-term mortality. There is a need for new agents that can be given in the acute setting with increased efficacy and safety. Istaroxime is a unique agent with both inotropic and lusitropic properties which is currently being studied for the treatment of AHFS. Istaroxime inhibits the sodium-potassium adenosine triphosphatase (ATPase) and stimulates the sarcoplasmic reticulum calcium ATPase isoform 2 (SERCA-2) thereby improving contractility and diastolic relaxation. Early data from human studies reveal that istaroxime decreases pulmonary capillary wedge pressure (PCWP) and possibly improves diastolic function without causing a significant change in heart rate (HR), blood pressure, ischemic or arrhythmic events. Most commonly reported side effects were related to gastrointestinal intolerance and were dose related. In conclusion, istaroxime is a novel agent being investigated for the treatment of AHFS whose mechanism of action and cellular targets make it a promising therapy. Further studies with longer infusion times in patients with hypotension are required to confirm its efficacy and safety.

journal_name

Heart Fail Rev

journal_title

Heart failure reviews

authors

Khan H,Metra M,Blair JE,Vogel M,Harinstein ME,Filippatos GS,Sabbah HN,Porchet H,Valentini G,Gheorghiade M

doi

10.1007/s10741-009-9136-z

subject

Has Abstract

pub_date

2009-12-01 00:00:00

pages

277-87

issue

4

eissn

1382-4147

issn

1573-7322

journal_volume

14

pub_type

杂志文章,评审
  • Heart transplantation in the young and elderly.

    abstract:INTRODUCTION:Heart transplantation has become an acceptable treatment in pediatric patients with end-stage heart disease and complex congenital heart disease. The liberalization of recipient eligibility criteria, mainly age, along with the expansion of the donor pool has resulted in the acceptable transplantation of ol...

    journal_title:Heart failure reviews

    pub_type: 杂志文章

    doi:10.1023/a:1011406022657

    authors: Laks H,Marelli D,Odim J,Fazio D

    更新日期:2001-09-01 00:00:00

  • The use of cognitive behavioral therapy in the treatment of depression for individuals with CHF.

    abstract::Patients diagnosed with CHF have disproportionately high rates of depression. Research has demonstrated significant consequences of depression in patients with CHF including poor quality of life, worse medical adherence and increased health complications, health care utilization, and medical costs. Despite these conse...

    journal_title:Heart failure reviews

    pub_type: 杂志文章,评审

    doi:10.1007/s10741-008-9081-2

    authors: O'Hea E,Houseman J,Bedek K,Sposato R

    更新日期:2009-03-01 00:00:00

  • Protective molecular mechanisms of clusterin against apoptosis in cardiomyocytes.

    abstract::Loss of cardiomyocytes occurs with aging and contributes to cardiovascular complications. In the present study, we highlighted the role of clusterin, a protein that has recently been associated with the protection of cardiomyocytes from apoptosis. Clusterin protects cardiac cells against damage from myocardial infarct...

    journal_title:Heart failure reviews

    pub_type: 杂志文章,评审

    doi:10.1007/s10741-017-9654-z

    authors: Pereira RM,Mekary RA,da Cruz Rodrigues KC,Anaruma CP,Ropelle ER,da Silva ASR,Cintra DE,Pauli JR,de Moura LP

    更新日期:2018-01-01 00:00:00

  • Arrhythmic complication in cardiorenal syndrome.

    abstract::In this paper, two different aspects of the relationship between chronic kidney disease and sudden cardiac death (SCD) have been reviewed. In end-stage renal disease patients, SCD risk is increased, and among patients implanted with a cardioverter defibrillator (ICD), dialysed ones carry a superior relative risk compa...

    journal_title:Heart failure reviews

    pub_type: 杂志文章,评审

    doi:10.1007/s10741-010-9210-6

    authors: Padeletti L,Innocenti L,Paoletti Perini A,Gronda E

    更新日期:2011-11-01 00:00:00

  • Advanced glycation end-products, a pathophysiological pathway in the cardiorenal syndrome.

    abstract::The prevalence of heart failure (HF) is increasing. A distinction is made between diastolic HF (preserved left ventricular ejection fraction (LVEF)) and systolic HF (reduced LVEF). Advanced glycation end-products (AGEs) are crystallized proteins that accumulate during ageing, but are particularly increased in patients...

    journal_title:Heart failure reviews

    pub_type: 杂志文章,评审

    doi:10.1007/s10741-010-9225-z

    authors: Willemsen S,Hartog JW,Heiner-Fokkema MR,van Veldhuisen DJ,Voors AA

    更新日期:2012-03-01 00:00:00

  • Classical inotropes and new cardiac enhancers.

    abstract::Acute heat failure syndromes are a heterogenous group of conditions. Chronic heart failure exacerbations represent the vast majority of cases. Pathophysiologic mechanisms, such as hypotension with peripheral tissue hypoperfusion, renal function impairment and myocardial ischemia and injury, adversely affect patients' ...

    journal_title:Heart failure reviews

    pub_type: 杂志文章,评审

    doi:10.1007/s10741-007-9014-5

    authors: Parissis JT,Farmakis D,Nieminen M

    更新日期:2007-06-01 00:00:00

  • In search of a standard when analyzing medication adherence in patients with heart failure using claims data: a systematic review.

    abstract::To determine and address medication non-adherence is important and may improve patient outcomes. Our aim was to perform a systematic review on the operationalization of adherence measures in patients with heart failure using claims data. We searched the MEDLINE, EMBASE, and Cochrane databases. A quality check of the f...

    journal_title:Heart failure reviews

    pub_type: 杂志文章

    doi:10.1007/s10741-017-9656-x

    authors: Krueger K,Griese-Mammen N,Schubert I,Kieble M,Botermann L,Laufs U,Kloft C,Schulz M

    更新日期:2018-01-01 00:00:00

  • Direct cardiovascular impact of SGLT2 inhibitors: mechanisms and effects.

    abstract::Diabetes is a global epidemic and a leading cause of death with more than 422 million patients worldwide out of whom around 392 million alone suffer from type 2 diabetes (T2D). Sodium-glucose cotransporter 2 inhibitors (SGLT2i) are novel and effective drugs in managing glycemia of T2D patients. These inhibitors gained...

    journal_title:Heart failure reviews

    pub_type: 杂志文章,评审

    doi:10.1007/s10741-017-9665-9

    authors: Kaplan A,Abidi E,El-Yazbi A,Eid A,Booz GW,Zouein FA

    更新日期:2018-05-01 00:00:00

  • Cor pulmonale: the role of traditional and advanced echocardiography in the acute and chronic settings.

    abstract::Cor pulmonale is the condition in which the right ventricle undergoes morphological and/or functional changes due to diseases that affect the lungs, the pulmonary circulation, or the breathing process. Depending on the speed of onset of the pathological condition and subsequent effects on the right ventricle, it is po...

    journal_title:Heart failure reviews

    pub_type: 杂志文章,评审

    doi:10.1007/s10741-020-10014-4

    authors: Mandoli GE,Sciaccaluga C,Bandera F,Cameli P,Esposito R,D'Andrea A,Evola V,Sorrentino R,Malagoli A,Sisti N,Nistor D,Santoro C,Bargagli E,Mondillo S,Galderisi M,Cameli M,Working group of Echocardiography of Italian Society

    更新日期:2020-08-29 00:00:00

  • New strategies for improving stem cell therapy in ischemic heart disease.

    abstract::Stem cell therapy is a promising approach to the treatment of ischemic heart disease via replenishing cell loss after myocardial infarction. Both preclinical studies and clinical trials have indicated that cardiac function improved consistently, but very modestly after cell-based therapy. This mainly attributed to low...

    journal_title:Heart failure reviews

    pub_type: 杂志文章,评审

    doi:10.1007/s10741-016-9576-1

    authors: Huang P,Tian X,Li Q,Yang Y

    更新日期:2016-11-01 00:00:00

  • Defining the role of ultrafiltration therapy in acute heart failure: a systematic review and meta-analysis.

    abstract::Ultrafiltration (UF) has emerged as an alternative therapy for acute decompensated heart failure (ADHF) due to its physiological benefits such as improvement in neurohormonal activation. We performed a systematic review and a meta-analysis to evaluate the efficacy, safety, and the impact on outcomes for UF therapy as ...

    journal_title:Heart failure reviews

    pub_type: 杂志文章,meta分析,评审

    doi:10.1007/s10741-016-9559-2

    authors: Jain A,Agrawal N,Kazory A

    更新日期:2016-09-01 00:00:00

  • Renin-angiotensin-system inhibition in the context of corona virus disease-19: experimental evidence, observational studies, and clinical implications.

    abstract::Coronavirus disease 2019 (COVID-19) is due to severe acute respiratory syndrome coronavirus (SARS-CoV)-2 which binds and enters the host cells through the angiotensin-converting enzyme (ACE)2. While the potential for benefit with the use of renin-angiotensin-aldosterone system inhibitors (RAASi) and the risks from sto...

    journal_title:Heart failure reviews

    pub_type: 杂志文章,评审

    doi:10.1007/s10741-020-10022-4

    authors: Triposkiadis F,Starling RC,Xanthopoulos A,Butler J,Boudoulas H

    更新日期:2020-09-01 00:00:00

  • B-type natriuretic peptide: physiologic role and assay characteristics.

    abstract::The discovery of cardiac natriuretic peptides two decades ago has lead to considerable research to investigate their biochemical and physiological properties. Clearly the heart is not just a pump but is also an endocrine organ that together with the kidneys control volume overload. The natriuretic peptides are a group...

    journal_title:Heart failure reviews

    pub_type: 杂志文章,评审

    doi:10.1023/a:1026182912461

    authors: Azzazy HM,Christenson RH

    更新日期:2003-10-01 00:00:00

  • Energy metabolism in the hypertrophied heart.

    abstract::In response to a prolonged pressure- or volume-overload, alterations occur in myocardial fatty acid, glucose, and glycogen metabolism. Oxidation of long chain fatty acids has been found to be reduced in hypertrophied hearts compared to non-hypertrophied hearts. However, this observation depends upon the degree of card...

    journal_title:Heart failure reviews

    pub_type: 杂志文章,评审

    doi:10.1023/a:1015380609464

    authors: Sambandam N,Lopaschuk GD,Brownsey RW,Allard MF

    更新日期:2002-04-01 00:00:00

  • Preconditioning in humans.

    abstract::Brief ischemia to the myocardium initiates a cascade of biochemical events in cardiac myocytes that protects the heart muscle during subsequent ischemic insults. This phenomenon is called ischemic preconditioning. If an acute myocardial infarction is preceded by preinfarction angina, it results in smaller infarction s...

    journal_title:Heart failure reviews

    pub_type: 杂志文章,评审

    doi:10.1007/s10741-007-9037-y

    authors: Rezkalla SH,Kloner RA

    更新日期:2007-12-01 00:00:00

  • β-Adrenergic receptor, an essential target in cardiovascular diseases.

    abstract::β-Adrenergic receptors (βARs) belong to a large family of cell surface receptors known as G protein-coupled receptors (GPCRs). They are coupled to Gs protein (Gαs) for the activation of adenylyl cyclase (AC) yielding cyclic AMP (CAMP), and this provides valuable responses, which can affect the cardiac function such as...

    journal_title:Heart failure reviews

    pub_type: 杂志文章,评审

    doi:10.1007/s10741-019-09825-x

    authors: Ali DC,Naveed M,Gordon A,Majeed F,Saeed M,Ogbuke MI,Atif M,Zubair HM,Changxing L

    更新日期:2020-03-01 00:00:00

  • Unraveling new mechanisms of exercise intolerance in chronic heart failure: role of exercise training.

    abstract::Despite remarkable progress in the therapeutic approach of patients with chronic heart failure (CHF), exercise intolerance remains one of the hallmarks of the disease. During the past two decades, evidence has accumulated to underscore the key role of both endothelial dysfunction and skeletal muscle wasting in the pro...

    journal_title:Heart failure reviews

    pub_type: 杂志文章,评审

    doi:10.1007/s10741-012-9324-0

    authors: Conraads VM,Van Craenenbroeck EM,De Maeyer C,Van Berendoncks AM,Beckers PJ,Vrints CJ

    更新日期:2013-01-01 00:00:00

  • Association of loop diuretics use and dose with outcomes in outpatients with heart failure: a systematic review and meta-analysis of observational studies involving 96,959 patients.

    abstract::There is ongoing controversy regarding the association between loop diuretics (LD), especially in high doses, and adverse clinical outcomes in outpatients with heart failure (HF). We performed a systematic review of the evidence for LD in outpatients with HF. We searched MEDLINE, EMBASE, and Cochrane Clinical Trial Co...

    journal_title:Heart failure reviews

    pub_type: 杂志文章,评审

    doi:10.1007/s10741-020-09995-z

    authors: Kapelios CJ,Bonou Μ,Malliaras K,Athanasiadi E,Vakrou S,Skouloudi M,Masoura C,Barbetseas J

    更新日期:2020-06-21 00:00:00

  • Bias in natriuretic peptide-guided heart failure trials: time to improve guideline adherence using alternative approaches.

    abstract::Treatment of patients with heart failure with reduced ejection fraction (HFrEF) with currently available therapies reduces morbidity and mortality. However, implementation of these therapies is a problem with only few patients achieving guideline-recommended maximal doses of therapy. In an effort to improve guideline ...

    journal_title:Heart failure reviews

    pub_type: 杂志文章,评审

    doi:10.1007/s10741-020-10004-6

    authors: Stienen S,Bhatt A,Ferreira JP,Vaduganathan M,Januzzi J,Adams K,Tardif JC,Rossignol P,Zannad F

    更新日期:2021-01-01 00:00:00

  • Sodium glucose cotransporter 2 inhibitors: mechanisms of action in heart failure.

    abstract::Diabetes is a key independent risk factor in the development of heart failure (HF) and a strong, adverse prognostic factor in HF patients. HF remains the primary cause of hospitalisation for diabetics and, as previous studies have shown, when HF occurs in these patients, intensive glycaemic control does not directly i...

    journal_title:Heart failure reviews

    pub_type: 杂志文章,评审

    doi:10.1007/s10741-020-10041-1

    authors: Dutka M,Bobiński R,Ulman-Włodarz I,Hajduga M,Bujok J,Pająk C,Ćwiertnia M

    更新日期:2020-11-04 00:00:00

  • Mechanistic implications of altered protein expression in rheumatic heart disease.

    abstract::Rheumatic heart disease (RHD) is a major cause of cardiovascular morbidity and mortality in low- and middle-income countries, where living conditions promote spread of group A β-haemolytic streptococcus. Autoimmune reactions due to molecular mimicry of bacterial epitopes by host proteins cause acute rheumatic fever (A...

    journal_title:Heart failure reviews

    pub_type: 杂志文章,评审

    doi:10.1007/s10741-020-09993-1

    authors: Lumngwena EN,Skatulla S,Blackburn JM,Ntusi NAB

    更新日期:2020-07-11 00:00:00

  • Prognostic significance of T1 mapping parameters in heart failure with preserved ejection fraction: a systematic review.

    abstract::Heart failure with preserved ejection fraction (HFpEF) accounts for almost one-half of all heart failure (HF) patients and continues to increase in prevalence. While mortality with heart failure with reduced ejection fraction (HFrEF) has decreased over the past few decades with use of evidence-based HFrEF therapy, mor...

    journal_title:Heart failure reviews

    pub_type: 杂志文章,评审

    doi:10.1007/s10741-020-09958-4

    authors: Moustafa A,Khan MS,Alsamman MA,Jamal F,Atalay MK

    更新日期:2020-05-13 00:00:00

  • Non-ischemic dilated cardiomyopathy and cardiac fibrosis.

    abstract::Cardiac fibrosis is associated with non-ischemic dilated cardiomyopathy, increasing its morbidity and mortality. Cardiac fibroblast is the keystone of fibrogenesis, being activated by numerous cellular and humoral factors. Macrophages, CD4+ and CD8+ T cells, mast cells, and endothelial cells stimulate fibrogenesis dir...

    journal_title:Heart failure reviews

    pub_type: 杂志文章,评审

    doi:10.1007/s10741-020-09940-0

    authors: Cojan-Minzat BO,Zlibut A,Agoston-Coldea L

    更新日期:2020-03-13 00:00:00

  • Clinical characteristics, demographics and prognosis of transient left ventricular apical ballooning syndrome.

    abstract:BACKGROUND:Transient left ventricular apical ballooning syndrome also called Tako-Tsubo cardiomyopathy is defined as a syndrome consisting of stress induced apical ballooning of the left ventricle and normal coronary arteries. The majority of the published reports are case reports or case series with a small number of ...

    journal_title:Heart failure reviews

    pub_type: 杂志文章,meta分析

    doi:10.1007/s10741-005-8555-8

    authors: Donohue D,Movahed MR

    更新日期:2005-12-01 00:00:00

  • Beyond the myocardium? SGLT2 inhibitors target peripheral components of reduced oxygen flux in the diabetic patient with heart failure with preserved ejection fraction.

    abstract::Recent cardiovascular outcome trials have highlighted the propensity of the antidiabetic agents, SGLT2 inhibitors (SGLT2is or -flozin drugs), to exert positive clinical outcomes in patients with cardiovascular disease at risk for major adverse cardiovascular events (MACEs). Of interest in cardiac diabetology is the ph...

    journal_title:Heart failure reviews

    pub_type: 杂志文章,评审

    doi:10.1007/s10741-020-09996-y

    authors: Nashawi M,Sheikh O,Battisha A,Mir M,Chilton R

    更新日期:2020-06-24 00:00:00

  • Diastolic heart failure in the elderly.

    abstract::It is now clear that diastolic heart failure (DHF) is an important, perhaps even dominant form of heart failure in older Americans. However, our knowledge base regarding the epidemiology, pathophysiology, natural history, and therapy of this relatively recently recognized disorder is limited. A number of normal age re...

    journal_title:Heart failure reviews

    pub_type: 杂志文章,评审

    doi:10.1023/a:1013745705318

    authors: Kitzman DW

    更新日期:2002-01-01 00:00:00

  • Metabolic and structural impairment of skeletal muscle in heart failure.

    abstract::Physiologic endurance exercise performance is primarily limited by cardiac function. In patients with heart failure, there is dissociation between cardiac performance and exercise capacity, suggesting a distinct role of abnormal peripheral organ function, including skeletal muscle function. The impact of heart failure...

    journal_title:Heart failure reviews

    pub_type: 杂志文章,评审

    doi:10.1007/s10741-012-9353-8

    authors: Zizola C,Schulze PC

    更新日期:2013-09-01 00:00:00

  • The role of erythropoiesis stimulating agents and intravenous (IV) iron in the cardio renal anemia syndrome.

    abstract::Anemia is common in Congestive Heart Failure (CHF) and is associated with an increased mortality, morbidity and progressive renal failure. The most common causes of the anemia in CHF are (1) the associated Chronic Kidney Disease (CKD), which causes depression of erythropoietin (EPO) production in the kidney, and (2) e...

    journal_title:Heart failure reviews

    pub_type: 杂志文章,评审

    doi:10.1007/s10741-010-9194-2

    authors: Silverberg DS

    更新日期:2011-11-01 00:00:00

  • Transthyretin amyloid cardiomyopathy in women: frequency, characteristics, and diagnostic challenges.

    abstract::Transthyretin amyloid cardiomyopathy (ATTR-CM) is a progressive, life-threatening disease characterized by deposition of insoluble amyloid fibrils in the myocardium, resulting in cardiac structural and functional abnormalities and ultimately heart failure. Disease frequency is reportedly lower in women than men, but s...

    journal_title:Heart failure reviews

    pub_type: 杂志文章,评审

    doi:10.1007/s10741-020-10010-8

    authors: Bruno M,Castaño A,Burton A,Grodin JL

    更新日期:2021-01-01 00:00:00

  • Loop diuretic resistance complicating acute heart failure.

    abstract::Acute heart failure hospitalizations complicated by diuretic resistance are associated with worse outcomes. Yet, quantification of the frequency and accompanying risk from loop diuretic resistance is limited by the absence of a comprehensive definition with universal clinical application. Herein, we outline limitation...

    journal_title:Heart failure reviews

    pub_type: 杂志文章,评审

    doi:10.1007/s10741-019-09851-9

    authors: Cox ZL,Testani JM

    更新日期:2020-01-01 00:00:00