Pulmonary Oedema—Therapeutic Targets

Chioncel, Ovidiu; Collins, Sean P.; Ambrosy, Andrew P.; Gheorghiade, Mihai; Filippatos, Gerasimos

doi:10.15420/cfr.2015.01.01.38

Cited by 15 publications

(7 citation statements)

References 83 publications

(102 reference statements)

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“…Similarly, although small studies suggest that vasodilators are preferable as first‐line therapy in AHF patients with hypertension, a definitive trial testing this strategy is required to fill this evidence void. Furthermore, no therapy has shown simultaneous benefits in symptomatic relief, haemodynamic improvement, increased survival and end‐organ protection . New methods such as thoracic impedance monitoring have been used to detect pulmonary oedema in the research setting …”

Section: Gaps In Knowledge and Future Directionsmentioning

confidence: 99%

Organ dysfunction, injury and failure in acute heart failure: from pathophysiology to diagnosis and management. A review on behalf of the Acute Heart Failure Committee of the Heart Failure Association (HFA) of the European Society of Cardiology (ESC)

Harjola

Mullens

Banaszewski

et al. 2017

European J of Heart Fail

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Organ injury and impairment are commonly observed in patients with acute heart failure (AHF), and congestion is an essential pathophysiological mechanism of impaired organ function. Congestion is the predominant clinical profile in most patients with AHF; a smaller proportion presents with peripheral hypoperfusion or cardiogenic shock. Hypoperfusion further deteriorates organ function. The injury and dysfunction of target organs (i.e. heart, lungs, kidneys, liver, intestine, brain) in the setting of AHF are associated with increased risk for mortality. Improvement in organ function after decongestive therapies has been associated with a lower risk for post-discharge mortality. Thus, the prevention and correction of organ dysfunction represent a therapeutic target of interest in AHF and should be evaluated in clinical trials. Treatment strategies that specifically prevent, reduce or reverse organ dysfunction remain to be identified and evaluated to determine if such interventions impact mortality, morbidity and patient-centred outcomes. This paper reflects current understanding among experts of the presentation and management of organ impairment in AHF and suggests priorities for future research to advance the field.

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Section: Gaps In Knowledge and Future Directionsmentioning

confidence: 99%

Organ dysfunction, injury and failure in acute heart failure: from pathophysiology to diagnosis and management. A review on behalf of the Acute Heart Failure Committee of the Heart Failure Association (HFA) of the European Society of Cardiology (ESC)

Harjola

Mullens

Banaszewski

et al. 2017

European J of Heart Fail

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300

256

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“…β-adrenergic compound agonists such as dopamine, terbutaline, and isoproterenol improve lung liquid clearance by upregulating NKA (Saldías et al, 2000;Saldías et al, 2002). At low concentrations, CG inhibits the enzyme, displaying cell signaling via NKA without interruption of ion-pump function, which is essential for edema clearance (Chioncel et al, 2015). The ion pump-independent action and signal transduction turn NKA into an important clinical treatment target.…”

Section: Nkamentioning

confidence: 99%

Na+/K+-ATPase as a Target of Cardiac Glycosides for the Treatment of SARS-CoV-2 Infection

et al. 2021

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Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), identified for the first time in Wuhan, China, causes coronavirus disease 2019 (COVID-19), which moved from epidemic status to becoming a pandemic. Since its discovery in December 2019, there have been countless cases of mortality and morbidity due to this virus. Several compounds such as chloroquine, hydroxychloroquine, lopinavir-ritonavir, and remdesivir have been tested as potential therapies; however, no effective treatment is currently recommended by regulatory agencies. Some studies on respiratory non-enveloped viruses such as adenoviruses and rhinovirus and some respiratory enveloped viruses including human respiratory syncytial viruses, influenza A, parainfluenza, SARS-CoV, and SARS-CoV-2 have shown the antiviral activity of cardiac glycosides, correlating their effect with Na+/K+-ATPase (NKA) modulation. Cardiac glycosides are secondary metabolites used to treat patients with cardiac insufficiency because they are the most potent inotropic agents. The effects of cardiac glycosides on NKA are dependent on cell type, exposure time, and drug concentration. They may also cause blockage of Na+ and K+ ionic transport or trigger signaling pathways. The antiviral activity of cardiac glycosides is related to cell signaling activation through NKA inhibition. Nuclear factor kappa B (NFκB) seems to be an essential transcription factor for SARS-CoV-2 infection. NFκB inhibition by cardiac glycosides interferes directly with SARS-CoV-2 yield and inflammatory cytokine production. Interestingly, the antiviral effect of cardiac glycosides is associated with tyrosine kinase (Src) activation, and NFκB appears to be regulated by Src. Src is one of the main signaling targets of the NKA α-subunit, modulating other signaling factors that may also impair viral infection. These data suggest that Src-NFκB signaling modulated by NKA plays a crucial role in the inhibition of SARS-CoV-2 infection. Herein, we discuss the antiviral effects of cardiac glycosides on different respiratory viruses, SARS-CoV-2 pathology, cell signaling pathways, and NKA as a possible molecular target for the treatment of COVID-19.

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“…In contrast, in acute pulmonary oedema, pulmonary congestion is predominantly due to an acute increase in afterload with a relative volume redistribution rather than an absolute fluid accumulation. 15 Overall, congestion and fluid overload (the wet haemodynamic profile) is the most common profile in patients presenting with AHF. Less than 10% of patients present with signs of hypoperfusion and low blood pressure (the cold haemodynamic profile).…”

mentioning

confidence: 99%

Congestion and Diuretic Resistance in Acute or Worsening Heart Failure

2020

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Hospitalisation for acute heart failure (AHF) is associated with high mortality and high rehospitalisation rates. In the absence of evidence-based therapy, treatment is aimed at stabilisation and symptom relief. The majority of AHF patients have signs and symptoms of fluid overload, and, therefore, decongestion is the number one treatment goal. Diuretics are the cornerstone of therapy in AHF, but the treatment effect is challenged by diuretic resistance and poor diuretic response throughout the spectrum of chronic to worsening to acute to post-worsening HF. Adequate dosing and monitoring and evaluation of diuretic effect are important for treatment success. Residual congestion at discharge is a strong predictor of worse outcomes. Therefore, achieving euvolaemia is crucial despite transient worsening renal function.

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Pulmonary Oedema—Therapeutic Targets

Cited by 15 publications

References 83 publications

Organ dysfunction, injury and failure in acute heart failure: from pathophysiology to diagnosis and management. A review on behalf of the Acute Heart Failure Committee of the Heart Failure Association (HFA) of the European Society of Cardiology (ESC)

Organ dysfunction, injury and failure in acute heart failure: from pathophysiology to diagnosis and management. A review on behalf of the Acute Heart Failure Committee of the Heart Failure Association (HFA) of the European Society of Cardiology (ESC)

Na+/K+-ATPase as a Target of Cardiac Glycosides for the Treatment of SARS-CoV-2 Infection

Congestion and Diuretic Resistance in Acute or Worsening Heart Failure

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