Treating volume overload in acutely decompensated heart failure: established and novel therapeutic approaches

Koniari, Katerina; Parissis, John; Paraskevaidis, Ioannis; Anastasiou-Nana, Maria

doi:10.1177/2048872612457044

Cited by 20 publications

(23 citation statements)

References 97 publications

(100 reference statements)

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“…Attempts at introducing novel drug therapies for AHF have been marked by numerous setbacks over the past two decades, with multiple promising agents stalling due to efficacy and/or safety concerns following clinical trials 6. Challenges to drug development include a complex and incompletely understood disease pathophysiology (figure 1),7 off-target and adverse drug effects, significant patient heterogeneity, clinical trial design logistics and financial cost 8. In contrast to the multiple beneficial therapies approved for chronic heart failure over the past decade, the treatment of AHF has not significantly changed for decades.…”

Section: Introductionmentioning

confidence: 99%

Serelaxin and acute heart failure

Tietjens

Teerlink

2015

Heart

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Attempts at developing novel therapeutic agents for acute heart failure (AHF) over the past two decades have been marked by disappointment. Relaxin is a human peptide hormone believed to mediate many adaptive haemodynamic changes that occur during pregnancy. Because these effects may be useful for treating AHF, a recombinant version of human relaxin-2, serelaxin, has been developed as a novel therapeutic agent. Studies have confirmed serelaxin's haemodynamic effects of decreasing pulmonary and systemic resistance and increasing renal blood flow. A 1161-patient, placebo-controlled Phase III trial, RELAX-AHF, demonstrated significant improvement in symptoms, reduced worsening of heart failure, decreased hospital length of stay and increased 180-day survival after index hospitalisation. Additional Phase III trials (RELAX-AHF-2; RELAX-AHF-ASIA) are underway to further evaluate the efficacy of serelaxin in patients with AHF. This article will review the physiological function, mechanism of action, clinical trial results and future directions of serelaxin in the treatment of AHF.

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Section: Introductionmentioning

confidence: 99%

Serelaxin and acute heart failure

Tietjens

Teerlink

2015

Heart

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“…For instance, elderly females with preserved EF tend to present more often with rapidly progressive pulmonary oedema in the setting of hypertension related to mechanisms of reduced arterial compliance and venous capacitance . Other patients present with a distinct phenotype characterized by the insidious onset of dyspnoea, and peripheral oedema with evidence of hepatic and renal dysfunction due, in part, to RAAS activation, inflammation, and progressive cardiorenal syndrome . Regardless of the specific underlying mechanisms for an individual patient, congestion contributes to HF progression through further neurohormonal activation, LV geometric changes, pulmonary hypertension, right ventricular (RV) dysfunction, and adverse cardiorenal changes …”

Section: Pathophysiology Of Congestion In Acute Heart Failurementioning

confidence: 99%

“…In addition to gut sequesterants, serelaxin, and novel natriuretic peptides such as ularitide, there are a number of additional AHF therapeutic agents with potential decongestion benefits that are currently under investigation. For instance, these agents include luso‐inotropic agents (istraoxime), cardiac myosin activators (omecamtiv mecarbil), and oral soluble guanylate cyclase stimulators, which have recently been reviewed . Further studies will be needed to clarify the utility of these and other agents with regard to decongestion.…”

Section: Other Novel Agents Under Investigationmentioning

confidence: 99%

Decongestion in acute heart failure

Mentz

Kjeldsen

Rossi

et al. 2014

European J of Heart Fail

126

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Congestion is a major reason for hospitalization in acute heart failure (HF). Therapeutic strategies to manage congestion include diuretics, vasodilators, ultrafiltration, vasopressin antagonists, mineralocorticoid receptor antagonists, and potentially also novel therapies such as gut sequesterants and serelaxin. Uncertainty exists with respect to the appropriate decongestion strategy for an individual patient. In this manuscript, we summarize the benefit and risk profiles for these decongestion strategies and provide guidance on selecting an appropriate approach for different patients. An evidence-based initial approach to congestion management involves high-dose intravenous diuretics with addition of vasodilators for dyspnea relief if blood pressure allows. To enhance diuresis or overcome diuretic resistance, options include dual nephron blockade with thiazide diuretics or natriuretic doses of mineralocorticoid receptor antagonists. Vasopressin antagonists may improve aquaresis and relieve dyspnea. If diuretic strategies are unsuccessful, then ultrafiltration may be considered. Ultrafiltration should be used with caution in the setting of worsening renal function. This review is based on discussions among scientists, clinical trialists and regulatory representatives at the 9th Global Cardio Vascular Clinical Trialists Forum in Paris, France, from November 30 to December 1, 2012.

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“…Congestion manifested as edema, dyspnea and fatigue is the primary reason for acute heart failure hospitalization [3]. Many patients show symptoms of congestion without gaining weight and it is therefore increasingly recognized that fluid redistribution contributes to acute heart failure, for instance via autonomic mechanisms, inflammation and abnormalities in adenosine signalling [4]. Hemodynamic parameters, such as the extravascular lung water index (EVLWI) have been shown to be associated with mortality in acute lung injury/acute respiratory distress syndrome (ALI/ARDS) and after resuscitation [5, 6].…”

Section: Introductionmentioning

confidence: 99%

Pulse contour cardiac output monitoring in acute heart failure patients

Wernly

Lichtenauer

Franz

et al. 2016

Wien Klin Wochenschr

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SummaryBackgroundHeart failure is known to be a major public health problem. Fluid redistribution contributes to acute heart failure; therefore, knowledge of hemodynamic parameters could be important for optimizing outcomes. The pulse contour cardiac output monitor PiCCO uses the single thermal indicator technique and pulse contour analysis to calculate hemodynamic parameters of preload, afterload, cardiac output, systemic vascular resistance and extravascular lung water.ObjectivesWe primarily aimed to describe values and parameters seen in acute heart failure patients admitted to the intensive care unit (ICU) and secondly to investigate associations between hemodynamic measurements and survival data.Material and methodsIn this study 420 consecutive patients admitted to a tertiary medical university hospital ICU between January 2004 and December 2009 were retrospectively investigated. The study sample was divided into two subgroups: patients monitored by PiCCO (n = 47) and those not monitored by thermodilution measurements (n = 373). No predetermined treatment algorithm based on knowledge obtained by the PiCCO monitor was used and measurements were individually interpreted by the treating physician. The PiCCO monitor measurements were carried out according to manufacturer’s directions.ResultsPatients with PiCCO monitoring were clinically in poorer health with a mean simplified acute physiology score II (SAPS2) of 45 ± 17 vs. 56 ± 20 (p < 0.01). The ICU mortality (22 % vs. 38 %, p = 0.02) and, at least as a tendency, long-term-mortality were increased in patients monitored by PiCCO (RR 1.49, 95 % CI 0.96–2.31, p = 0.08). We provide hemodynamic measurements in acute heart failure patients: cardiac index (2.7 ± 1.2 l/min/m²) was reduced, preload and extravascular lung water index (EVLWI, 11.5 ± 5.1 ml/kg body weight), representing lung edema, were increased.ConclusionWe provide real world values for PiCCO parameters in acutely decompensated heart failure. In our study patients who were clinically in poorer health were monitored with PiCCO, resulting in increased mortality in this group. Further prospective studies to investigate the effects of treatment decisions triggered by information obtained by PiCCO monitoring for patients in acute heart failure are needed.

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Treating volume overload in acutely decompensated heart failure: established and novel therapeutic approaches

Abstract: Further clinical studies are required in order to determine their net effect on renal function and potential cardiovascular outcomes. Until then, management of volume overload in ADHF patients remains a challenge for the clinicians.

Cited by 20 publications

References 97 publications

Serelaxin and acute heart failure

Serelaxin and acute heart failure

Decongestion in acute heart failure

Pulse contour cardiac output monitoring in acute heart failure patients

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