scholarly journals Pathophysiology and Therapeutic Approaches to Acute Decompensated Heart Failure

2021 ◽  
Vol 128 (10) ◽  
pp. 1468-1486
Author(s):  
Joyce N. Njoroge ◽  
John R. Teerlink
Keyword(s):  
Heart Failure ◽  
Acute Decompensated Heart Failure ◽  
Unmet Need ◽  
Decompensated Heart Failure ◽  
Cardiovascular Death ◽  
New Drugs ◽  
Therapeutic Approaches ◽  
Life Saving ◽  
Risk Patients ◽  
Hospital Morbidity

Acute decompensated heart failure (ADHF) is one of the leading admission diagnoses worldwide, yet it is an entity with incompletely understood pathophysiology and limited therapeutic options. Patients admitted for ADHF have high in-hospital morbidity and mortality, as well as frequent rehospitalizations and subsequent cardiovascular death. This devastating clinical course is partly due to suboptimal medical management of ADHF with persistent congestion upon hospital discharge and inadequate predischarge initiation of life-saving guideline-directed therapies. While new drugs for the treatment of chronic HF continue to be approved, there has been no new therapy approved for ADHF in decades. This review will focus on the current limited understanding of ADHF pathophysiology, possible therapeutic targets, and current limitations in expanding available therapies in light of the unmet need among these high-risk patients.

The clinical impact of delirium in the patients with acute decompensated heart failure

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
Y.A Aikawa ◽  
T.N Noguchi ◽  
I.M Morii
Keyword(s):  
Heart Failure ◽  
Acute Decompensated Heart Failure ◽  
Multivariable Analysis ◽  
Composite Endpoint ◽  
Decompensated Heart Failure ◽  
Cardiovascular Death ◽  
Clinical Impact ◽  
Hospital Death ◽  
Early Screening ◽  
H2 Blocker

Abstract Background Delirium is frequent in-hospital complication in patients with illness. However, the clinical impact of delirium on cardiovascular mortality has not been fully addressed in patients with acute decompensated heart failure (ADHF). Methods Between April 2016 and May 2019, 474 consecutive patients with ADHF admitted to our institution were enrolled and followed for 6 months after discharge. Delirium was defined according to the Intensive Care Delirium Checklist. To compare the clinical outcome, we divided study patients into 3 groups according to the presence or absence of delirium: non-delirium (ND) (n=349), improved-delirium during hospitalization (ID) (n=68), and prolonged delirium (PD) (n=57). Results One hundred twenty-five (26.4%) patients developed delirium. During hospitalization, PD had higher incidence of all-cause death, cardiovascular death, and worsening heart failure compared with ND and ID (20.0% vs. 3.7% and 2.9%, 10.9% vs. 2.5% and 1.4%, 21.8% vs. 2.5% and 4.3%, p<0.001, respectively). Multivariable analysis identified the presence of frailty (OR: 8.56, 95% CI: 3.46–23.7) and dementia (OR: 7.34, 95% CI: 3.52–15.9), use of H2-blocker (OR: 3.41, 95% CI: 1.08–10.9) and plasma level of CRP (OR: 1.30, 95% CI: 1.06–1.61) as significant independent determinants of delirium. Also, in multivariable analysis, the development of frailty (OR: 5.51, 95% CI: 2.80–11.5), delirium (OR: 4.59, 95% CI: 2.23–9.66) and age (OR: 1.06, 95% CI: 1.03–1.11) were the independent determinants of composite endpoint with in-hospital death and discharge to other than home. Early treatment of delirium performed significantly higher in ID than PD (55.7% vs. 29.1%, p=0.003). Conclusion This study suggested that PD contributed to increasing in-hospital events in the patients with ADHF and significance of early screening and treatment for delirium. Figure 1. Outcomes during hospitalization Funding Acknowledgement Type of funding source: None

Natriuretic peptide analogues with distinct vasodilatory or renal activity: integrated effects in health and experimental heart failure

2020 ◽  
Author(s):  
Miriam T Rademaker ◽  
Nicola J A Scott ◽  
Cho Yeow Koh ◽  
R Manjunatha Kini ◽  
A Mark Richards
Keyword(s):  
Heart Failure ◽  
Blood Pressure ◽  
Natriuretic Peptide ◽  
Acute Decompensated Heart Failure ◽  
Unmet Need ◽  
Urine Volume ◽  
Plasma Renin ◽  
Decompensated Heart Failure ◽  
Guanosine Monophosphate ◽  
High Dose

Abstract Aims Management of acute decompensated heart failure (ADHF) requires disparate treatments depending on the state of systemic/peripheral perfusion and the presence/absence of expanded body–fluid volumes. There is an unmet need for therapeutics that differentially treat each aspect. Atrial natriuretic peptide (ANP) plays an important role in blood pressure and volume regulation. We investigate for the first time the integrated haemodynamic, endocrine and renal effects of human ANP analogues, modified for exclusive vasodilatory (ANP-DRD) or diuretic (ANP-DGD) activities, in normal health and experimental ADHF. Methods and results We compared the effects of incremental infusions of ANP analogues ANP-DRD and ANP-DGD with native ANP, in normal (n = 8) and ADHF (n = 8) sheep. ANP-DRD administration increased plasma cyclic guanosine monophosphate (cGMP) in association with dose-dependent reductions in arterial pressure in normal and heart failure (HF) sheep similarly to ANP responses. In contrast to ANP, which in HF produced a diuresis/natriuresis, this analogue was without significant renal effect. Conversely, ANP-DGD induced marked stepwise increases in urinary cGMP, urine volume, and sodium excretion in HF comparable to ANP, but without accompanying vasodilatory effects. All peptides increased packed cell volume relative to control in both states, and in HF, decreased left atrial pressure. In response to ANP-DRD-induced blood pressure reductions, plasma renin activity rose compared to control only during the high dose in normals, and not at all in HF—suggesting relative renin inhibition, with no increase in aldosterone in either state, whereas renin and aldosterone were both significantly reduced by ANP-DGD in HF. Conclusion These ANP analogues exhibit distinct vasodilatory (ANP-DRD) and diuretic/natriuretic (ANP-DGD) activities, and therefore have the potential to provide precision therapy for ADHF patients with differing pathophysiological derangement of pressure–volume homeostasis.

scholarly journals Biomarkers In Acute Heart Failure — Cardiac And Kidney

2015 ◽  
Vol 1 (2) ◽  
pp. 107 ◽  
Author(s):  
A Mark Richards ◽  
◽  
Keyword(s):  
Heart Failure ◽  
Brain Natriuretic Peptide ◽  
Natriuretic Peptide ◽  
Test Performance ◽  
Acute Decompensated Heart Failure ◽  
Unmet Need ◽  
Kidney Injury ◽  
High Sensitivity ◽  
Decompensated Heart Failure ◽  
Predictive Values

Natriuretic peptides (NP) are well-validated aids in the diagnosis of acute decompensated heart failure (ADHF). In acute presentations, both brain natriuretic peptide (BNP) and N-terminal of the prohormone brain natriuretic peptide (NT-proBNP) offer high sensitivity (>90 %) and negative predictive values (>95 %) for ruling out ADHF at thresholds of 100 and 300 pg/ml, respectively. Plasma NP rise with age. For added rule-in performance age-adjusted thresholds (450 pg/ml for under 50 years, 900 pg/ml for 50—75 years and 1,800 pg/ml for those >75 years) can be applied to NT-proBNP results. Test performance (specificity and accuracy but not sensitivity) is clearly reduced by renal dysfunction and atrial fibrillation. Obesity offsets the threshold downwards (to ~50 pg/ml for BNP), but overall discrimination is preserved. Reliable markers for impending acute kidney injury in ADHF constitute an unmet need, with candidates, such as kidney injury molecule-1 and neutrophil gelatinase-associated lipocalin, failing to perform sufficiently well, and new possibilities, including the cell cycle markers insulin growth factor binding protein 7 and tissue inhibitor of metalloproteinases type 2, remain the subject of research.

scholarly journals Intra-cardiac microcomputer allows for innovative telemedicine in chronic heart failure during coronavirus disease-2019 pandemic: a case report

2020 ◽  
Author(s):  
Sebastian Feickert ◽  
Giuseppe D’Ancona ◽  
Monica Murero ◽  
Hüseyin Ince
Keyword(s):  
Heart Failure ◽  
High Risk ◽  
Chronic Heart Failure ◽  
Acute Decompensated Heart Failure ◽  
Decompensated Heart Failure ◽  
Disease Spread ◽  
Case Summary ◽  
Infective Disease ◽  
Risk Patients

Abstract Background  Heart failure patient management guided by invasive intra-cardiac and pulmonary pressure measurements through permanent intra-cardiac micro-sensors has recently been published as a strategy to individualize the therapy of patients with chronic heart failure to reduce re-hospitalization and optimize quality of life. Furthermore, the use of telemedicine could have an important impact on infective disease spread during the current coronavirus disease-2019 pandemic. Case summary  Emergent hospitalization of a patient with acute on chronic heart failure, who is currently in self-isolation as a result of his comorbid profile that exposes him to high risk for severe course and mortality in case of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection was prevented using a last generation telemedicine tool. Discussion  Further implementation of invasive telemedicine could prevent hospitalization for acute decompensated heart failure and consecutive exposure to a potential hospital infection with SARS-CoV-2 in high-risk patients.

scholarly journals C-reactive protein at discharge and 1-year mortality in hospitalised patients with acute decompensated heart failure: an observational study

BMJ Open ◽  
2020 ◽  
Vol 10 (12) ◽  
pp. e041068
Author(s):  
Yuji Nishimoto ◽  
Takao Kato ◽  
Takeshi Morimoto ◽  
Hidenori Yaku ◽  
Yasutaka Inuzuka ◽  
...  
Keyword(s):  
Heart Failure ◽  
Mortality Risk ◽  
Excess Mortality ◽  
Acute Decompensated Heart Failure ◽  
Decompensated Heart Failure ◽  
Cardiovascular Death ◽  
Secondary Outcome ◽  
Link Type ◽  
Hospitalised Patients

ObjectivesTo examine the association of a high C-reactive protein (CRP) level at discharge from an acute decompensated heart failure (ADHF) hospitalisation with the 1-year clinical outcomes.DesignA post-hoc subanalysis of a prospective cohort study of patients hospitalised for ADHF (using the Kyoto Congestive Heart Failure (KCHF) registry) between October 2014 and March 2016 with a 1-year follow-up.SettingA physician-initiated multicentre registry enrolled consecutive hospitalised patients with ADHF for the first time at 19 secondary and tertiary hospitals in Japan.ParticipantsAmong the 4056 patients enrolled in the KCHF registry, the present study population consisted of 2618 patients with an available CRP value both on admission and at discharge and post-discharge clinical follow-up data. We divided the patients into two groups, those with a high CRP level (>10 mg/L) and those with a low CRP level (≤10 mg/L) at discharge from the index hospitalisation.Primary and secondary outcome measuresThe primary outcome measure was all-cause death after discharge from the index hospitalisation. The secondary outcome measures were heart failure hospitalisations, cardiovascular death and non-cardiovascular death.ResultsThe high CRP group and low CRP group included 622 patients (24%) and 1996 patients (76%), respectively. During a median follow-up period of 468 days, the cumulative 1-year incidence of the primary outcome was significantly higher in the high CRP group than low CRP group (24.1% vs 13.9%, log-rank p<0.001). Even after a multivariable analysis, the excess mortality risk in the high CRP group relative to the low CRP group remained significant (HR, 1.43; 95% CI, 1.19 to 1.71; p<0.001). The excess mortality risk was consistent regardless of the clinically relevant subgroup factors.ConclusionsA high CRP level (>10 mg/L) at discharge from an ADHF hospitalisation was associated with an excess mortality risk at 1 year.Trial registration detailshttps://clinicaltrials.gov/ct2/show/NCT02334891 (NCT02334891) https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000017241 (UMIN000015238).

1135Angiotensin receptor-neprilysin inhibition in patients with de novo acute decompensated heart failure: a prespecified subgroup analysis of the PIONEER-HF trial

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
A Ambrosy ◽  
E Braunwald ◽  
D Morrow ◽  
A Devore ◽  
K McCague ◽  
...  
Keyword(s):  
Heart Failure ◽  
De Novo ◽  
Acute Decompensated Heart Failure ◽  
Decompensated Heart Failure ◽  
The United States ◽  
Cardiovascular Death ◽  
P Value ◽  
Double Blind ◽  
Neprilysin Inhibitor ◽  
History Of

Abstract Background The efficacy, safety, and tolerability of an angiotensin receptor-neprilysin inhibitor (ARNi) in patients presenting with de novo heart failure (HF) has not been previously well-defined. Methods The PIONEER-HF trial was a prospective, multicenter, double-blind, active-controlled, randomized clinical trial which enrolled 887 patients (pts) at 129 sites in the United States. Pts with or without a history of prior HF and an ejection fraction (EF) <40% and a NT-proBNP >1600 pg/mL or BNP >400 pg/mL were eligible for participation no earlier than 24 hours while still hospitalized for acute decompensated HF (ADHF). Pts were randomly assigned 1:1 to in-hospital initiation of sacubitril/valsartan (S/V) titrated to 97/103 mg vs. enalapril titrated to 10 mg both by mouth twice daily for 8 weeks. We performed a pre-specified analysis in pts with de novo HF (i.e., defined as pts without a history of HF prior to the qualifying ADHF event). Results At the time of enrollment, 34% (N=303) had de novo HF. These pts experienced a similar improvement in NT-proBNP with S/V vs. enalapril (Ratio of geometric means 0.65, 95% Confidence Interval [CI] 0.53–0.81; p-value = 0.0002) compared to pts with worsening chronic HF (ratio 0.72 (0.63–0.83, p-value <0.0001) (Figure). In addition, the incidence of worsening renal function, hyperkalemia, and hypotension was comparable with S/V vs. enalapril regardless of whether they were hospitalized for de novo or worsening chronic HF. Finally, there was no interaction (p-value = 0.350) between previous HF status and the effect of S/V on the composite of cardiovascular death or rehospitalization for HF (de novo HF: Hazard Ratio [HR] 0.34, 95% CI 0.11–1.05 vs. worsening chronic HF: HR 0.60, 95% CI 0.39–0.93). Conclusion Among patients admitted for ADHF, irrespective of prior HF history, in-hospital initiation of an ARNi led to a greater reduction in natriuretic peptide levels, a comparable safety profile, and a significant improvement in clinical outcomes. Acknowledgement/Funding Novartis

scholarly journals Cardiovascular biomarkers in patients with acute decompensated heart failure randomized to sacubitril-valsartan or enalapril in the PIONEER-HF trial

2019 ◽  
Vol 40 (40) ◽  
pp. 3345-3352 ◽  
Author(s):  
David A Morrow ◽  
Eric J Velazquez ◽  
Adam D DeVore ◽  
Margaret F Prescott ◽  
Carol I Duffy ◽  
...  
Keyword(s):  
Heart Failure ◽  
Acute Decompensated Heart Failure ◽  
High Sensitivity ◽  
Decompensated Heart Failure ◽  
Cardiovascular Death ◽  
Double Blind ◽  
Reduced Ejection Fraction ◽  
Treatment Groups ◽  
Myocardial Stress ◽  
Patients With Heart Failure

Abstract Aims Circulating high-sensitivity cardiac troponin (hsTn) and soluble ST2 (sST2) reflect myocardial stress in patients with heart failure (HF). Production of cyclic guanosine 3′5′ monophosphate (cGMP) in response to activation of natriuretic peptide receptors reduces cardiac afterload and preload. We assessed the effects of sacubitril/valsartan on these biomarkers in patients with reduced ejection fraction and acute decompensated HF (ADHF). Methods and results PIONEER-HF was a randomized, double-blind trial of sacubitril/valsartan vs. enalapril in hospitalized patients with ADHF following haemodynamic stabilization. We measured circulating hsTnT, sST2, and urinary cGMP at baseline, 1, 2 (sST2, cGMP), 4, and 8 weeks (n = 694 with all baseline biomarkers). Ratios of geometric means (timepoint/baseline) were determined and compared as a ratio for sacubitril/valsartan vs. enalapril. Compared with enalapril, sacubitril/valsartan led to a significantly greater decline in hsTnT and sST2. This effect emerged as early as 1 week for sST2 and was significant for both at 4 weeks with a 16% greater reduction in hsTnT (P < 0.001) and 9% greater reduction in sST2 (P = 0.0033). Serial urinary cGMP increased with sacubitril/valsartan compared with enalapril (P < 0.001, 1 week). The significant differences between treatment groups for each biomarker were sustained at 8 weeks. In an exploratory multivariable-adjusted analysis of cardiovascular death or HF-rehospitalization, the concentrations of hsTnT, sST2 at week 1 were significantly associated with subsequent outcome. Conclusion Biomarkers of myocardial stress are elevated in patients with ADHF and associated with outcome. Compared with enalapril, sacubitril/valsartan reduces myocardial injury and haemodynamic stress as reflected by biomarkers, with an onset that is apparent within 1–4 weeks. Clinical trials registration NCT 02554890 clinical.trials.gov

scholarly journals SOFA score and short-term mortality in acute decompensated heart failure

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Adi Elias ◽  
Reham Agbarieh ◽  
Walid Saliba ◽  
Johad Khoury ◽  
Fadel Bahouth ◽  
...  
Keyword(s):  
Heart Failure ◽  
High Risk ◽  
Hospital Mortality ◽  
Sofa Score ◽  
Acute Decompensated Heart Failure ◽  
Decompensated Heart Failure ◽  
Short Term ◽  
High Risk Patients ◽  
Short Term Mortality ◽  
Risk Patients

AbstractAcute decompensated heart failure (ADHF) is one of the leading causes for hospitalization and mortality. Identifying high risk patients is essential to ensure proper management. Sequential Organ Function Assessment Score (SOFA) is considered an excellent score to predict short-term mortality in sepsis and other life-threatening conditions. To assess the capability of SOFA score in predicting short-term mortality in ADHF. We retrospectively identified patients with first hospitalization with primary diagnosis of ADHF between the years (2008–2018). The SOFA score was calculated for all patients. A total 3232 patients were included in the study. The SOFA score was significantly associated with in-hospital mortality and 30-day mortality. The odds ratios for 1-point increase in the SOFA score were 1.86 (95% CI 1.68–1.96) and 1.627 (95% CI 1.523–1.737) respectively. The SOFA Score demonstrated a good predictive accuracy. The areas under the curve of receiver operating characteristic curves for in-hospital mortality and 30-day mortality were 0.765 (95% CI 0.733–0.798) and 0.706 (95% CI 0.676–0.736) respectively. SOFA score is associated with increased risk of short-term mortality in ADHF. SOFA can be used as a complementary risk score to screen high risk patients who need strict monitoring.

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