Treatment Of Acute Heart Failure Research Articles

2023 Focused Update of the 2021 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure.

2023 Focused Update of the 2021 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure.

Impact of Different Right Ventricular Lead Positions on QRS Complex Duration Post Cardiac Resynchronization Therapy Device Implantation

Abstract Aim and objectives The aim of the study was to evaluate the effect of different RV lead positions on QRS complex duration post CRT device implantation in patients indicated for CRT as a treatment of chronic heart failure based on the recommendations of ESC guidelines for diagnosis and treatment of acute and chronic heart failure published in 2016 and to assess the effect of change of QRS complex duration and morphology according to different RV lead positions on clinical response. Patients and Methods This study included 100 patients (age 60.02 ± 7.18) post CRT device implantation presented for follow up at electrophysiology clinics of the cardiology department of Ain Shams university hospitals at least 3 months post CRT device implantation, during the period form from December 2020 till May 2021. The patients were divided into 2 groups according to the site of RV lead implantation after confirmation of the RV lead position by fluoroscope in Right anterior oblique (RAO) and left anterior oblique (LAO) views, 54 patients had the RV lead implanted in the RV Apex (RVA n = 54) and 46 patients had the RV lead implanted in the RV Septum (RVS n = 46). Results OF the total 100 patients that enrolled in our study the rate of non-responders was 19% of the patients showed no clinical improvement, no improvement of NYHA class by at least one grade, 30% of the patients were non-Echocardiographic responders, no improvement of LVEF (Δ EF) by at least 5% with no decrease of LVES diameter by at least 15%, and 15% of the patient were nonECG responders, delta QRS (ΔQRS) didn`t increase by at least 20%. There was no significant difference between the two groups regarding clinical response (NYHA class) (P-value = 0.583), LVEF (Δ EF 6.26 ± 1.64 in RVS group vs. 6.07 ± 1.67 in RVA group, P-value = 0.575) LVES diameter (47.70 ± 8.03 in RVS group vs. 45.39 ± 7.48 in RVA group, P-value = 0.141) or QRS complex narrowing (ΔQRS 60.93 ± 24.68 in RVS group vs. 54.07 ± 26.12 in RVA group, P-value = 0.182). There was no significant difference in the rate of non-responders between the two groups (clinical non responders in RVS group n = 8 vs. RVA group n = 11, P value = 0.547) (Echo non responders in RVS group n = 13 vs. RVA group n = 17, P value = 0.726) (ECG non responders in RVS group n = 6 vs. RVA group n = 9, P value = 0.613), There was an inverse relationship between ΔQRS and clinical response (NYHA) class post CRT device implantation in both RVS and RVA groups (P value 0.016 in RVS group, P value 0.007 in RVA group). Conclusion The study demonstrates that septal RV pacing in CRT is non-inferior to apical RV pacing regarding the primary objective of the study regarding clinical outcome, narrowing of QRS complex (ΔQRS) or LV reverse remodeling, thus no recommendation for optimal RV lead position can hence be drawn from this study. Also, delta QRS complex duration may be used as indicator for electric remodeling and CRT response.

Methodology for evaluating the effectiveness of the disease management program in patients with chronic heart failure

Chronic heart failure (CHF) is one of the urgent problems of modern healthcare, has a large-scale socio-economic nature and requires special understanding and comprehensive study. After each remission of CHF, complete restoration of the original functional state of the cardiovascular system does not occur, and in this regard, an important task in the treatment of patients with CHF, especially in the early stages of development, is prevention of its progression and daily medication. To address the issues of improving the quality of life as the main indicator of CHF therapy, in the modern world recommendations for the diagnosis and treatment of acute and chronic heart failure, along with mandatory optimal drug therapy, a special role is given to patient education with an emphasis on self-care and adherence to therapy. To evaluate the results, I have developed a methodology for evaluating this program. Since there is currently no express method of evaluating this program in the conditions of a polyclinic.

The prognostic value of improving congestion on lung ultrasound during treatment for acute heart failure differs based on patient characteristics at admission

BackgroundLung ultrasound congestion scoring (LUS-CS) is a congestion severity biomarker. The BLUSHED-AHF trial demonstrated feasibility for LUS-CS-guided therapy in acute heart failure (AHF). We investigated two questions: 1) does change (∆) in LUS-CS from emergency department (ED) to hospital-discharge predict patient outcomes, and 2) is the relationship between in-hospital decongestion and adverse events moderated by baseline risk-factors at admission? MethodsWe performed a secondary analysis of 933 observations/128 patients from 5 hospitals in the BLUSHED-AHF trial receiving daily LUS. ∆LUS-CS from ED arrival to inpatient discharge (scale −160 to +160, where negative = improving congestion) was compared to a primary outcome of 30-day death/AHF-rehospitalization. Cox regression was used to adjust for mortality risk at admission [Get-With-The-Guidelines HF risk score (GWTG-RS)] and the discharge LUS-CS. An interaction between ∆LUS-CS and GWTG-RS was included, under the hypothesis that the association between decongestion intensity (by ∆LUS-CS) and adverse outcomes would be stronger in admitted patients with low-mortality risk but high baseline congestion. ResultsMedian age was 65 years, GWTG-RS 36, left ventricular ejection fraction 36 %, and ∆LUS-CS −20. In the multivariable analysis ∆LUS-CS was associated with event-free survival (HR = 0.61; 95 % CI: 0.38–0.97), while discharge LUS-CS (HR = 1.00; 95%CI: 0.54–1.84) did not add incremental prognostic value to ∆LUS-CS alone. As GWTG-RS rose, benefits of LUS-CS reduction attenuated (interaction p < 0.05). ∆LUS-CS and event-free survival were most strongly correlated in patients without tachycardia, tachypnea, hypotension, hyponatremia, uremia, advanced age, or history of myocardial infarction at ED/baseline, and those with low daily loop diuretic requirements. ConclusionsReduction in ∆LUS-CS during AHF treatment was most associated with improved readmission-free survival in heavily congested patients with otherwise reassuring features at admission. ∆LUS-CS may be most useful as a measure to ensure adequate decongestion prior to discharge, to prevent early readmission, rather than modify survival.

Randomized controlled trial of urinE chemiStry guided aCute heArt faiLure treATmEnt (ESCALATE): Rationale and design

Diuresis to achieve decongestion is a central aim of therapy in patients hospitalized for acute decompensated heart failure (ADHF). While multiple clinical trials have investigated initial diuretic strategies for a designated period of time, there is a paucity of evidence to guide diuretic titration strategies continued until decongestion is achieved. The use of urine chemistries (urine sodium and creatinine) in a natriuretic response prediction equation accurately estimates natriuresis in response to diuretic dosing, but a randomized clinical trial is needed to compare a urine chemistry-guided diuresis strategy with a strategy of usual care. The urinE chemiStry guided aCute heArt faiLure treATmEnt (ESCALATE) trial is designed to test the hypothesis that protocolized diuretic therapy guided by spot urine chemistry through completion of intravenous diuresis will be superior to usual care and improve outcomes over the 14 days following randomization. ESCALATE will randomize and obtain complete data on 450 patients with acute heart failure to a diuretic strategy guided by urine chemistry or a usual care strategy. Key inclusion criteria include an objective measure of hypervolemia with at least 10 pounds of estimated excess volume, and key exclusion criteria include significant valvular stenosis, hypotension, and a chronic need for dialysis. Our primary outcome is days of benefit over the 14 days after randomization. Days of benefit combines patient symptoms captured by global clinical status with clinical state quantifying the need for hospitalization and intravenous diuresis. Clinical trial registrationNCT04481919.

Analytical Representation of Four-dimensional Hemodynamics for Drug Therapy Simulation in Acute Heart Failure Treatment.

Acute heart failure imperils multiple organs, including the heart. Elucidating the impact of drug therapies across this multidimensional hemodynamic system remains a challenge. This paper proposes a simulator that analyzes the impact of drug therapies on four dimensions of hemodynamics: left atrial pressure, cardiac output, mean arterial pressure, and myocardial oxygen consumption. To mathematically formulate hemodynamics, the analytical solutions of four-dimensional hemodynamics and the direction of its change are derived as functions of cardiovascular parameters: systemic vascular resistance, cardiac contractility, heart rate, and stressed blood volume. Furthermore, a drug library which represents the multi-dependency effect of drug therapies on cardiovascular parameters was identified in animal experiments. In evaluating the accuracy of our derived hemodynamic direction, the average angular error of predicted versus observed direction was 18.85[deg] after four different drug infusions for acute heart failure in animal experiments. Finally, the impact of drug therapies on four-dimensional hemodynamics was analyzed in three different simulation settings. One result showed that, even when drug therapies were simulated with simple rules according to the Forrester classification, the predicted direction of hemodynamic change matched the expected direction in more than 80% in 963 different AHF patient scenarios. Our developed simulator visualizes the impact of drug therapies on four-dimensional hemodynamics so intuitively that it can support clinicians' decision-making to protect multiple organs.

Novel application potential of cinaciguat in the treatment of mixed hyperlipidemia through targeting PTL/NPC1L1 and alleviating intestinal microbiota dysbiosis and metabolic disorders

Mixed hyperlipidemia, characterized by high levels of triglycerides and cholesterol, is a key risk factor leading to atherosclerosis and other cardiovascular diseases. Existing clinical drugs usually only work on a single indicator, decreasing either triglyceride or cholesterol levels. Developing dual-acting agents that reduce both triglycerides and cholesterol remains a great challenge. Pancreatic triglyceride lipase (PTL) and Niemann–Pick C1-like 1 (NPC1L1) have been identified as crucial proteins in the transport of triglycerides and cholesterol. Here, cinaciguat, a known agent used in the treatment of acute decompensated heart failure, was identified as a potent dual inhibitor targeting PTL and NPC1L1. We presented in vitro evidence from surface plasmon resonance analysis that cinaciguat interacted with PTL and NPC1L1. Furthermore, cinaciguat exhibited potent PTL-inhibition activity. Fluorescence-labeled cholesterol uptake analysis and confocal imaging showed that cinaciguat effectively inhibited cholesterol uptake. In vivo evaluation showed that cinaciguat significantly reduced the plasma levels of triglycerides and cholesterol, and effectively alleviated high-fat diet–induced intestinal microbiota dysbiosis and metabolic disorders. These results collectively suggest that cinaciguat has the potential to be further developed for the therapy of mixed hyperlipidemia.

Overview of the Treatment of Congestion in Heart Failure.

Heart failure is a major problem in developed countries, leading to a high number of hospitalizations and healthcare costs. The most common symptom of heart failure is congestion, which is also the primary reason for hospitalization. Diuretics, particularly loop diuretics, are the cornerstone of the treatment of congestion. Likewise, there are other types of diuretics with different pathways of action, bioavailability profiles, adverse reactions, and effects on the cardiovascular and renal systems. Moreover, in recent years, new therapeutic alternatives have been proposed for challenging cases of diuretic resistance, such as ultrafiltration through peripheral access or peritoneal dialysis. The main objective of this article is to provide a step-guided approach to the management of congestion in patients with heart failure in order to guide the medical practice. Despite the significant amount of research published in recent years, there are no clear algorithms for managing acute heart failure. Diuretics remain the primary treatment of acute heart failure, and nephron blockade is key, but new therapies are emerging, and ongoing research is needed to develop better strategies for managing this condition.

P334 PHARMACOUTILIZATION AND ADHERENCE TO SACUBITRIL/VALSARTAN IN REAL–WORLD: THE REAL.IT STUDY IN HEART FAILURE WITH REDUCED EJECTION FRACTION

Abstract Aims The current European Society of Cardiology guidelines provide clear indication for the treatment of acute and chronic heart failure (HF).Nevertheless,there is the constant need of real–world evidence concerning the effectiveness,adherence and persistence to drug therapy.We investigated the use of sacubitril/valsartan for the treatment of HF with reduced ejection fraction in real–world clinical practice in Italy. Methods An observational, retrospective,non–interventional cohort study based on electronic medical records from nine specialized hospital heart failure Centers in Italy was carried out on patients prescribed with sacubitril/valsartan. Results Overall,948 patients had a prescription of sacubitril/valsartan, 924 (mean age 64.5 years, 84.6% male) had 6 months of characterization and 12 months of follow–up. The initial dose was 24/26 mg for 548 (59.3%),49/51 mg for 333 (36.0%),97/103 mg for 43 (4.7).The final dose was available for 881 patients and it was:24/26 mg for 254 (28.8%),49/51 mg for 229 (26.0%),97/103 mgfor 398 (45.2).The time to maximal dose prescribed (weeks) was:for 97/103 mg 6.9 ± 6.2 weeks;for 49/51 mg 6.2 ± 6.7 weeks.Blood pressure and hypotension in 65% of the patients, and worsening of chronic kidney disease in 10.6% were the main reasons for not reaching target dose; fifty percent had a change in sacubitril/valsartan dose during follow–up and 70.2% patients were persistent with treatment during the last three months of follow–up, with a sensitivity analysis (persistence during the last four months of follow–up) showing 72.0% persistence. Adherence data, available for 387 patients, showed fully adherence for 53%.Discontinuation (102/387 patients) was mainly due to hypotension and occurred after a mean time of 34.3 ± 28.7 weeks. During follow–up, of the 606 patients with available data, 434 patients (71.6%) had an HF add–on drug or drugs concomitant to sacubitril/valsartan. Although not significantly (p=0.405), HF–related hospitalization during follow–up was higher in not persistent patients (23.9%) versus persistent (19%) to sacubitril/valsartan treatment.Pharmacoutilization data at 1–year expressed as medication possession ratio (MPR) are shown in the Figure. Conclusions Real–world data of sacubitril/valsartan use in clinical practice in Italy show a rapid titration of to target dose, high therapeutic adherence allowing a good level of therapeutic management in line with ESC guidelines in patients with reduced ejection fraction.

Zhenwu Decoction:connotation interpretation based on severe cases and modern pathophysiological mechanisms and application in treatment of heart failure in critical care unit

Zhenwu Decoction is recorded in Treatise on Febrile Diseases by an outstanding physician ZHANG Zhong-jing in the Han dynasty. With effect of warming yang, transforming Qi, and promoting urination, Zhenwu Decoction is mainly used to treat edema due to yang deficiency. The studies of the severe and critical cases and the pathophysiological mechanisms have demonstrated that the record of Zhenwu Decoction in Treatise on Febrile Diseases describes the clinical symptoms and therapeutic regimen of acute heart failure. The syndrome treated by this formula may be related to the misdiagnosis and wrong treatment. Due to the difficult distinguishing between cardiogenic dyspnea and pulmonary dyspnea, high doses of Ephedrae Herba may be misused for inducing sweating, which may finally lead to the acute aggravation of heart failure, electrolyte disorder, and pulmonary infection. The syndrome treated by Zhenwu Decoction can illustrate the lack of experience of ancient physicians in treating acute heart failure. The description of &quot;trembling and shivering&quot; may be the clinical manifestation of heart failure, which is an upgraded version of &quot;trembling and shaking&quot; treated by Linggui Zhugan Decoction.(1)In terms of diseases, Zhenwu Decoction is suitable for the treatment of acute or chronic heart failure, cardiorenal syndrome, and diuretic resistance. The decoction is especially suitable for treating whole heart failure, acute heart failure, heart failure with reduced ejection fraction, and heart failure with the syndrome of sold and dampness. In addition, it can be used to treat both type Ⅱ and type Ⅳ cardiorenal syndrome.(2)In terms of symptoms, Zhenwu Decoction can be used for treating chest tightness, palpitations, lower limb edema, difficult urination or increased urine output, fear of cold, pale fat tongue with teeth marks, white and slippery tongue fur, and deep or slow pulse.(3)In terms of the pharmacological mechanism, Zhenwu Decoction treats heart failure following the principle of promoting urination, expanding blood vessels, and invigorating heart in modern medicine. Aconiti Lateralis Radix Praparata is the sovereign herb in the formula, with the recommended dosage of 30-60 g. However, arrhythmia may be caused by high doses of Aconiti Lateralis Radix Praparata, which should be used with concern. In addition to Zhenwu Decoction, Shenqi Pills, Renshen Decoction, Wuling Powder, and Fangji Huangqi Decoction with the effect of invigorating spleen, replenishing Qi, warming Yang, and promoting urination can be used in the recovery stage. The therapy of reinforcing Yang was the last choice for critical cases due to the lack of medical conditions, unclear clinical diagnosis in history, which should be treated objectively now.

Heart failure therapy: the fifth card.

The 2021 European Society of Cardiology guidelines for the diagnosis and treatment of acute and chronic heart failure (HF) have abandoned the sequential approach for optimal drug therapy and propose four drug classes (enzyme inhibitors conversion agents, angiotensin receptor antagonists, beta-blockers, and sodium-glucose cotransporter inhibitors 2) to be initiated and titrated in all patients with an ejection fraction <35%. This new approach offers advantages such as rapid introduction and titration, better tolerability, and early instrumental re-evaluation. In the VICTORIA study, the molecule vericiguat, a soluble guanylate cyclase activator, was shown to reduce the composite outcome of death from cardiovascular causes and first hospitalization for HF in a high-risk population. An additional randomized clinical trial (VICTOR) is ongoing to evaluate the efficacy and safety of vericiguat in a population with HF on optimized therapy and with no recent episodes of stabilization.

Transcatheter Aortic Valve Replacement for Aortic Valve Infective Endocarditis: A Systematic Review and Call for Action.

We aimed to systematically analyze the literature on the use of transcatheter aortic valve replacement (TAVR) to treat active aortic valve infective endocarditis (AV-IE). Surgery is declined in one-third of patients with IE who meet indications because of prohibitive surgical risk. TAVR might be an alternative for selected patients with AV-IE as a bridge-to-surgery or stand-alone therapy. PubMed/MEDLINE, Embase, and Cochrane databases were searched (2002-2022) for studies on TAVR use in active AV-IE. Of 450 identified reports, six met inclusion criteria (all men, mean age 71 ± 12years, median Society of Thoracic Surgeons (STS) score 27, EuroSCORE 56). All patients were prohibitive surgical risk candidates. Five out of six patients had severe, and one patient had moderate aortic regurgitation on presentation. Five out of six patients had prosthetic valve endocarditis after surgical valve replacement 13years before (median), and one patient had TAVR a year before hospitalization. All patients had cardiogenic shock as the indication for TAVR. Four patients received balloon-expanding, and two patients received self-expanding TAVR after a median of 19(IQR 9-25) days from diagnosis of IE. No death or myocardial infarction occurred, but one patient had a stroke within the first 30days. The median event-free time was 9 (IQR 6-14) months including no death, reinfection, relapse IE, or valve-related rehospitalization. Our review suggests that TAVR can be considered as an adjuvant therapy to medical treatment for selected patients in whom surgery is indicated for treatment of acute heart failure due to aortic valve destruction and incompetence caused by infective endocarditis, but who have a prohibitive surgical risk. Nonetheless, a well-designed prospective registry is urgently needed to investigate the outcomes of TAVR for this off-label indication. No evidence exists for using the TAVR to treat infection-related surgical indications such as uncontrolled infection or control of septic embolization.

Global differences in acute heart failure treatment: analysis of the STRONG-HF site feasibility questionnaire.

Acute heart failure (AHF) has an impact on human health worldwide. Despite guidelines for treatment and management of AHF, mortality rates remain high. The main objective of this study was to compare standard in-hospital treatment and management of AHF against current clinical guidelines and variations across regions. Between February 2018 and May 2021, investigators were approached to participate in the STRONG-HF study. The lead investigator at 158 sites in 20 countries completed a site feasibility questionnaire. Sites were grouped by country into five different regions: Africa and the Middle East, Eastern Europe, Russia, South America, and Western Europe. According to the questionnaires, there are large differences in how patients present due to AHF and where in the hospital they are treated. There were significant differences in reported percentage of AHF patients receiving angiotensin converting enzymes inhibitors across the regions (P<0.001), mostly due to prescription of more angiotensin II receptor blockers and angiotensin receptor-neprilysin inhibitors in South America and Western Europe. Reported beta-blocker use was high across all of the regions. Device therapy and percutaneous interventions were more common in Europe. Sites reported a 5 to 8day length of stay, while in Russia most have a 10 to 12day length of stay. Regions reported that AHF patients follow up with a community cardiologist or general practitioner post-discharge, although follow-up was commonly more than 1month post discharge, and not all sites had the capability to measure natriuretic peptides post discharge. In this analysis of feasibility questionnaires, most sites reported general adherence to ESC guidelines for treatment and management of AHF patients although percutaneous and device therapy was less common outside Europe and follow-up after discharge took place late and was not as extensive as recommended. There were wide variations seen within and across regions in some areas.

Structural insights into angiotensin receptor signaling modulation by balanced and biased agonists.

The peptide hormone angiotensin II regulates blood pressure mainly through the type 1 angiotensin II receptor AT1 R and its downstream signaling proteins Gq and β-arrestin. AT1 R blockers, clinically used as antihypertensive drugs, inhibit both signaling pathways, whereas AT1 R β-arrestin-biased agonists have shown great potential for the treatment of acute heart failure. Here, we present a cryo-electron microscopy (cryo-EM) structure of the human AT1 R in complex with a balanced agonist, Sar1 -AngII, and Gq protein at 2.9 Å resolution. This structure, together with extensive functional assays and computational modeling, reveals the molecular mechanisms for AT1 R signaling modulation and suggests that a major hydrogen bond network (MHN) inside the receptor serves as a key regulator of AT1 R signal transduction from the ligand-binding pocket to both Gq and β-arrestin pathways. Specifically, we found that the MHN mutations N1113.35 A and N2947.45 A induce biased signaling to Gq and β-arrestin, respectively. These insights should facilitate AT1 R structure-based drug discovery for the treatment of cardiovascular diseases.

25 In-hospital Change in Lung Ultrasound Congestion Score Predicts Heart Failure Rehospitalization and Death: Implications for Clinical Trials

OBJECTIVES/GOALS: Lung Ultrasound Congestion Score (LUS-CS) is a proposed measure for guiding treatment in acute heart failure (AHF). An emergency department (ED) pilot trial of LUS-guided diuresis showed reduced LUS-CS at 48 hours but no difference at hospital discharge or for clinical outcomes. We hypothesized total change in LUS-CS would predict adverse outcomes. METHODS/STUDY POPULATION: This was a post-hoc secondary analysis of the BLUSHED-AHF trial. BLUSHED-AHF was a pilot trial in which AHF patients were randomized to a LUS-guided diuresis strategy vs. usual care in the ED. The intervention was stopped after the ED course (i.e. during hospitalization). BLUSHED-AHF was designed for the intervention to target absolute values of LUS-CS over time, rather than change in LUS-CS from each patient’s baseline. We fit a cox regression model for a primary outcome of death or AHF rehospitalization, with total (ED to Hospital Discharge) change in LUS-CS as the primary predictor, adjusted for the Get-With-The-Guidelines heart failure risk score (GWTG). Survival curves were plotted, and hazard ratios calculated. RESULTS/ANTICIPATED RESULTS: 128 patients in BLUSHED-AHF were analyzed. Greater reduction in LUS-CS from ED to hospital discharge predicted event-free survival (HR = 0.74 for each 20 unit reduction in LUS-CS, 95%CI 0.56-0.99). This effect did not vary by hospitalization length or ED disposition. There was a significant interaction between change in LUS-CS and GWTG score (p DISCUSSION/SIGNIFICANCE: LUS-CS total change, and not absolute values, predict adverse events in LUS-guided diuresis. Post-ED cessation of the intervention in BLUSHED-AHF may have precluded opportunity for clinical benefit. Future trials should run the entire hospital course, target change from baseline, and consider patient selection by AHF severity and initial LUS-CS.

Time-Dependent Changes in N-Terminal Pro-Brain Natriuretic Peptide and B-Type Natriuretic Peptide Ratio During Hospitalization for Acute Heart Failure.

The time-dependent changes in the simultaneous evaluation of B-type natriuretic peptide (BNP) and N-terminal pro-BNP (NT-proBNP) levels during hospitalization for acute heart failure (AHF) remain obscure.A total of 356 AHF patients were analyzed. Blood samples were collected within 15 minutes of admission (Day 1), 48-120 hours (Day 2-5) and between days 7 and 21 (Before-discharge). Plasma BNP and serum NT-proBNP were significantly decreased on Days 2-5 and Before-discharge in comparison to Day 1, but the NT-proBNP/BNP ratio was not changed. Patients were divided into 2 groups according to the median NT-proBNP/BNP (N/B) ratio on Day 2-5 (Low-N/B versus High-N/B). A multivariate logistic regression model showed that age (per 1-year increase), serum creatinine (per 1.0-mg/dL increase), and serum albumin (per 1.0-mg/dL decrease) were independently associated with High-N/B (odds ratio [OR]: 1.071, 95%confidence interval [CI]: 1.036-1.108, OR: 1.190, 95%CI: 1.121-1.264 and OR: 2.410, 95%CI: 1.121-5.155, respectively). Kaplan-Meier curve analysis showed that the High-N/B group had a significantly poorer prognosis than the Low-N/B group, and a multivariate Cox regression model revealed that High-N/B was an independent predictor of 365-day mortality (hazard ratio [HR]: 1.796, 95%CI: 1.041-3.100) and HF events (HR: 1.509, 95%CI: 1.007-2.263). The same trend in prognostic impact was significantly observed in both low and high delta-BNP cohorts (< 55% and ≥ 55% BNP value on the start date/BNP value at 2-5-days).A high NT-proBNP/BNP ratio on Day 2-5 was associated with non-cardiac conditions and was associated with adverse outcomes even if BNP was adequately decreased by the treatment of AHF.

The Effects of the Levosimendan Metabolites OR-1855 and OR-1896 on Endothelial Pro-Inflammatory Responses

The calcium sensitizer levosimendan is used for the treatment of acute decompensated heart failure. A small portion (4-7%) of levosimendan is metabolized to the pharmacologically active metabolite OR-1896 via the inactive intermediate OR-1855. In addition, levosimendan has been shown to exert positive effects on the endothelium in vitro antagonizing vascular dysfunction and inflammation. However, the function of the levosimendan metabolites within this context is still unknown. In this study, we thus investigated the impact of the metabolites OR-1896 and OR-1855 on endothelial inflammatory processes in vitro. We observed a reduction of IL-1β-dependent endothelial adhesion molecule ICAM-1 and VCAM-1 as well as interleukin (IL) -6 expression upon levosimendan treatment but not after treatment with OR-1855 or OR-1896, as assessed by western blotting, flow cytometry, and qRT-PCR. Instead, the metabolites impaired IL-1β-induced ROS formation via inactivation of the MAPK p38, ERK1/2, and JNK. Our results suggest that the levosimendan metabolites OR-1896 and OR-1855 have certain anti-inflammatory properties, partly other than levosimendan. Importantly, they additionally show that the intermediate metabolite OR-1855 does, in fact, have pharmacological effects in the endothelium. This is interesting, as the metabolites are responsible for the long-term therapeutic effects of levosimendan, and heart failure is associated with vascular dysfunction and inflammation.

Current diagnostic algorithms for chronic heart failure with preserved left ventricular ejection fraction

Chronic heart failure remains one of the main causes of mortality and reduced life quality both in Ukraine and around the world. More than 50 % of all patients with chronic heart failure are those with preserved left ventricular ejection fraction. In current guidelines, the criteria for evaluating heart failure with reduced left ventricular ejection fraction are described properly, but the issue of timely diagnosing chronic heart failure with preserved ejection fraction still remains unsolved. This review presents four diagnostic algorithms for this condition, which were presented by international scientific societies in recent years: 2021 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure; H2FPEF Score for Heart Failure with Preserved Ejection Fraction (Mayo, 2018); HFA-PEFF diagnostic algorithm: a consensus recommendation from the Heart Failure Association (HFA) of the European Society of Cardiology (ESC) (2019); Multimodality imaging in patients with heart failure and preserved ejection fraction: an expert consensus document of the European Association of Cardiovascular Imaging (2021). The main advantages, limitations and disadvantages of each one are analyzed. All steps of diagnostic evaluation are described in detail. The review is illustrated with patterns of the latest diagnostic approaches.

Sacubitril-valsartan versus enalapril for the treatment of acute decompensated heart failure in Chinese settings: A cost-effectiveness analysis.

Background: The episode of acute decompensated heart failure (ADHF) is the main cause of hospitalization for heart failure (HF). Sacubitril-valsartan has been proven to be effective in reducing the risks of hospitalization for HF in ADHF. When to initiate sacubitril-valsartan in ADHF to make it the most cost-effective in China remains unclear. Methods: A lifetime Markov model with a 1-month cycle length was developed to evaluate the cost-effectiveness of early or late initiation of sacubitril-valsartan versus enalapril in ADHF. Early initiation of sacubitril-valsartan meant that it was initiated after stabilization from ADHF, and late initiation of sacubitril-valsartan meant that it was initiated after stabilization from HF, which includes no hospitalization for at least three consecutive months. The primary outcome was the incremental cost-effectiveness ratio (ICER), expressed as the ratio of incremental cost to incremental effectiveness. The secondary outcomes were total costs and total effectiveness. Three times of per capita GDP of China in 2021 was set as the willingness-to-pay threshold. One-way sensitivity analysis and probabilistic sensitivity analysis were employed to test the robustness of the results. Results: The early initiation of sacubitril-valsartan treatment resulted in an ICER of 3,662.4 USD per quality-adjusted life year, lower than the willingness-to-pay threshold, and the late initiation of sacubitril-valsartan treatment gained an ICER of 4,444.4 USD/QALY, still lower than the willingness-to-pay threshold. One-way sensitivity analysis showed that our results were robust, and probabilistic sensitivity analysis suggested that early initiation of sacubitril-valsartan in ADHF was cost-effective under a 97.4% circumstance. Conclusion: Early initiation of sacubitril-valsartan after stabilization of ADHF is highly cost-effective compared with the use of enalapril; late initiation of sacubitril-valsartan after stabilization of HF is still cost-effective but not as cost-effective as early initiation of sacubitril-valsartan in ADHF. For Chinese ADHF patients, the time to initiate sacubitril-valsartan should be when the patient is stabilized from ADHF rather than when stabilized from HF, from the perspective of economic evaluation.

Successful treatment with ivabradine in a β‐blocker‐refractory patient with acute decompensated heart failure with reduced ejection fraction

Ivabradine is an established treatment for chronic heart failure with reduced ejection fraction (HFrEF); however, it is not used for acute heart failure treatment. Negative inotropic effects (NIE) often limit the up-titration of β-blockers. Contrarily, ivabradine has no NIE, and enables β-blockers usage for treating patients with acute decompensated HFrEF.