Iron Deficiency, Anemia, and Iron Supplementation in Patients With Heart Failure: A Population-Level Study.

BACKGROUND: Studies have shown an association between iron deficiency (ID) and clinical outcomes in patients with heart failure (HF), irrespective of the presence of ID anemia (IDA). The current study used population-level data from a large, single-payer health care system in Canada to investigate the epidemiology of ID and IDA in patients with acute HF and those with chronic HF, and the iron supplementation practices in these settings. METHODS: All adult patients with HF in Alberta between 2012 and 2019 were identified and categorized as acute or chronic HF. HF subtypes were determined through echocardiography data, and ID (serum ferritin concentration <100 µg/L, or ferritin concentration between 100 and 300 µg/L along with transferrin saturation <20%), and IDA through laboratory data. Broad eligibility for 3 clinical trials (AFFIRM-AHF [Study to Compare Ferric Carboxymaltose With Placebo in Patients With Acute HF and ID], IRONMAN [Intravenous Iron Treatment in Patients With Heart Failure and Iron Deficiency], and HEART-FID [Randomized Placebocontrolled Trial of Ferric Carboxymaltose as Treatment for HF With ID]) was determined. RESULTS: Among the 17 463 patients with acute HF, 38.5% had iron studies tested within 30 days post-index-HF episode (and 34.2% of the 11 320 patients with chronic HF). Among tested patients, 72.6% of the acute HF and 73.9% of the chronic HF were iron-deficient, and 51.4% and 49.0% had IDA, respectively. Iron therapy was provided to 41.8% and 40.5% of patients with IDA and acute or chronic HF, respectively. Of ID patients without anemia, 19.9% and 21.7% were prescribed iron therapy. The most common type of iron therapy was oral (28.1% of patients). Approximately half of the cohort was eligible for each of the AFFIRM-AHF, intravenous iron treatment in patients with HF and ID, and HEART-FID trials. CONCLUSIONS: Current practices for investigating and treating ID in patients with HF do not align with existing guideline recommendations. Considering the gap in care, innovative strategies to optimize iron therapy in patients with HF are required.

Imbalance of Iron Availability and Demand in Patients With Acute and Chronic Heart Failure.

BACKGROUND: Iron deficiency (ID) is a frequent comorbidity in patients with acute (AHF) and chronic heart failure (CHF) associated with morbidity and death. We aimed to better characterize iron homeostasis in patients with heart failure applying different biomarkers and to evaluate the accuracy of current ID definition by the European Society of Cardiology/American College of Cardiology/American Heart Association to indicate tissue iron availability and demand. METHODS AND RESULTS: We performed a retrospective cohort study investigating 277 patients with AHF and 476 patients with CHF between February 2021 and May 2022. Patients with AHF had more advanced ID than patients with CHF, reflected by increased soluble transferrin receptor and soluble transferrin receptor-ferritin index, and lower ferritin, serum iron, transferrin saturation, hepcidin, and reticulocyte hemoglobin. Decreased iron availability or increased tissue iron demand, reflected by increased soluble transferrin receptor-ferritin index and decreased reticulocyte hemoglobin, was found in 84.1% (AHF) and 28.0% (CHF) with absolute ID and in 50.0% (AHF) and 10.5% (CHF) with combined ID according to the current European Society of Cardiology/American College of Cardiology/American Heart Association-based ID definition. Low hepcidin expression as an indicator of systemic ID was found in 91.1% (AHF) and 80.4% (CHF) of patients with absolute ID and in 32.3% (AHF) and 18.8% (CHF) of patients with combined ID. ID definitions with higher specificity reduce the need for iron supplementation by 25.5% in patients with AHF and by 65.6% in patients with CHF. CONCLUSIONS: Our results suggest that the current European Society of Cardiology/American College of Cardiology/American Heart Association-based ID definition might overestimate true ID, particularly in CHF. More stringent thresholds for ID could more accurately identify patients with heart failure with reduced tissue iron availability who benefit from intravenous iron supplementation.

[Network Meta-analysis of different Chinese medicine injections combined with conventional western medicine in treatment of acute heart failure].

This study aims to evaluate the efficacy and safety of Chinese medicine injection in the treatment of acute heart failure. PubMed, Cochrane Library, EMbase, Web of Science, CNKI, VIP, Wanfang, and SinoMed were searched for the randomized controlled trial(RCT) of Chinese medicine injection combined with conventional western medicines in the treatment of acute heart failure with the time interval from the inception to July 10, 2023. Two researchers independently screened the literature, extracted data, and evaluated the risk of bias in the included studies. Stata 15.1 was used to perform network Meta-analysis. A total of 117 RCTs were included, involving 10 529 patients and 7 Chinese medicine injections: Shenfu Injection, Shenmai Injection, Danhong Injection, Puera-rin Injection, Xinmailong Injection, Shengmai Injection, and Yiqi Fumai Injection. Network Meta-analysis yielded the following results.(1) In terms of improving the total response rate, the surface under the cumulative ranking curve(SUCRA) ranking was Shengmai Injection + conventional western medicine > Danhong Injection + conventional western medicine > Shenmai Injection + conventio-nal western medicine > Shenfu Injection + conventional western medicine > Xinmailong Injection + conventional western medicine > Yiqi Fumai Injection + conventional western medicine > Puerarin Injection + conventional western medicine > conventional western medicine.(2)In terms of reducing brain natriuretic peptide(BNP), the SUCRA ranking was Danhong Injection + conventional western medicine > Xinmailong Injection + conventional western medicine > Yiqi Fumai Injection + conventional western medicine > Shenfu Injection + conventional western medicine > Shenmai Injection + conventional western medicine > Puerarin Injection + conventional wes-tern medicine > Shengmai Injection + conventional western medicine > conventional western medicine.(3)In terms of reducing N-terminal pro-brain natriuretic peptide(NT-proBNP), the SUCRA ranking was Shenmai Injection + conventional western medicine > Yiqi Fumai Injection + conventional western medicine > Xinmailong Injection + conventional western medicine > Shengmai Injection + conventional western medicine > Shenfu Injection + conventional western medicine > Puerarin Injection + conventional western medicine > Danhong Injection + conventional western medicine > conventional western medicine.(4) In terms of improving the left ventricular ejection fraction(LVEF), the SUCRA ranking was Shenmai Injection + conventional western medicine > Xinmailong Injection + conventional western medicine > Shenfu Injection + conventional western medicine > Yiqi Fumai Injection + conventional western medicine > Puerarin Injection + conventional western medicine > Danhong Injection + conventional western medicine > Shengmai Injection + conventional western medicine > conventional western medicine.(5) In terms of decreasing the left ventricular end-diastolic diameter(LVEDD), the SUCRA ranking was Shenmai Injection + conventional western medicine > Shenfu Injection + conventional western medicine=Xinmailong Injection + conventional western medicine > Shengmai Injection + conventional western medicine > Yiqi Fumai Injection + conventional western medicine > conventional western medicine > Puerarin Injection + conventional western medicine.(6) In terms of increasing the 6-min walk trail(6MWT), the SUCRA ranking was Xinmailong Injection + conventional western medicine > Shenfu Injection + conventional western medicine > Shenmai Injection + conventional western medicine > Yiqi Fumai Injection + conventional western medicine > conventional western medicine.(7) In terms of reducing the Minnesota heart failure quality of life scale(MLHFQ) scores, the SUCRA ranking was Xinmailong Injection + conventional western medicine > Shenmai Injection + conventional western medicine > Shenfu Injection + conventional western medicine > conventional western medicine.(8)In terms of safety, the group of Chinese medicine injection combined with conventional western medicine had lower incidence of adverse reactions than the control group. The current evidence shows that combining Chinese medicine injection with conventional western medicine treatment can improve the therapeutic effect on acute heart failure, with high safety. Due to the limited number and quality of included studies, the above conclusions need to be verified by more high-quality studies.

Use of Autotransfusion following Percutaneous Thrombectomy for Cardiogenic Shock Due to Pulmonary Embolism in a Single Session-A Case Report.

A 64-year-old male patient was admitted to the catheterization laboratory with a suspected myocardial infarction and in cardiogenic shock. Upon further investigation, a massive bilateral pulmonary embolism with signs of right heart dysfunction was discovered, leading to a decision to perform a direct interventional treatment with a thrombectomy device for thrombus aspiration. The procedure was successful in removing almost the entirety of the thrombotic material from the pulmonary arteries. The patient's hemodynamics stabilized and oxygenation improved instantly. The procedure required a total of 18 aspiration cycles. Each aspiration contained approx. 60 mL blood amounting to a total of approx. 1080 mL of blood. During the procedure, a mechanical blood salvage system was used to resupply 50% of the blood via autotransfusion that would otherwise have been lost. The patient was transferred to the intensive care unit for post-interventional care and monitoring. A CT angiography of the pulmonary arteries after the procedure confirmed the presence of only minor residual thrombotic material. The patient's clinical, ECG, echocardiographic, and laboratory parameters returned to normal or near normal ranges. The patient was discharged shortly after in stable conditions on oral anticoagulation.

Differences in clinical outcomes between octogenarian and nonagenarian patients with acute heart failure.

AIM: The number of hospitalized super-elderly patients with heart failure (HF) has increased with aging of the population. These patients are associated with poor clinical outcomes with the advance of age; however, few reports regarding acute HF have compared the clinical outcomes of nonagenarians with those of octogenarians. METHODS: This study enrolled 683 patients aged ≥80 years who were admitted to our institution for acute HF between 2016 and 2020. The outcomes of interest were the 1-year all-cause mortality, incidence of cardiac events (cardiac-related death or HF-related readmission), and physical function during hospitalization of patients with survival-to-discharge. Physical function was evaluated using the Barthel index. RESULTS: Post-discharge all-cause mortality, particularly non-cardiac mortality, was significantly higher in nonagenarians than octogenarians. Conversely, the incidence of cardiac death or rehospitalization for HF after discharge was comparable between the two groups. On admission, the Barthel index score was significantly lower in nonagenarians than octogenarians, and further decreased during hospitalization. Nonagenarians required social support at discharge more often than octogenarians (67.4% vs. 44.4%; P < 0.001). CONCLUSIONS: The current study demonstrated that nonagenarians have poorer non-cardiac outcomes and were more vulnerable regarding physical activities than octogenarians among patients with acute HF. Holistic medical care, including palliative care and social support, will be increasingly required with increasing age. Geriatr Gerontol Int 2023; 23: 227-233.

Efficacy and Safety of Shenfu Injection on Acute Heart Failure: A Systematic Review and Meta-Analysis.

BACKGROUND: The adjunctive efficacy and safety of Shenfu Injection (SFI) for acute heart failure (AHF) still remains ambiguous even though previous studies made initial conclusions. OBJECTIVE: To comprehensively evaluate the adjunctive efficacy and safety of SFI in the treatment of AHF. STUDY DESIGN: This was a meta-analysis and systematic review. METHODS: 8 databases were searched for qualified randomized controlled trials (RCTs) from May 1990 to May 2022. The primary results included total clinical effective rate (TCER) and left ventricular ejection fraction (LVEF). The secondary results included left ventricular end diastolic dimension (LVEDD), heart rate (HR), N-terminal pro-B-type natriuretic peptide (NT-proBNP), brain natriuretic peptide (BNP) and adverse events (AE). The quality evaluation, meta-analysis, sensitivity analysis, subgroup analysis and publication bias were conducted by RevMan5.3 software. Meta-regression analysis was conducted using Stata software 15.0, and trial sequential analyses (TSA) was performed by TSA program. Finally, the GRADE (Grading of Recommendation, Assessment, Development, and Evaluation) system was applied for evaluating the quality of evidence. RESULTS: 61 RCTs containing 5505 AHF patients were included. The meta results demonstrated SFI combined with conventional western treatment (CWT) for AHF was superior to CWT alone in improving the TCER (RR = 1.21; 95% CI (1.18, 1.24); p < 0.001), improving LVEF (SMD = 0.85; 95% CI (0.77,0.92); p < 0.001) and reducing HR (SMD = -0.67; 95% CI (0.80, -0.54) p < 0.001). It had a lower AE rate in the SFI+CWT group (27/753, 3.59%) than the CWT group (68/739, 9.20%) (RR = 0.40; 95% CI (0.26, 0.61); p < 0.001). The outcomes' evidentiary quality of TCER, HR, LVEF and AE were assessed as moderate. CONCLUSION: Adjunctive use of SFI was safer to improve TCER and heart function of AHF, but the results should be interpreted with cautious for clinical practice until high quality-designed RCTs were require for further confirmation due to poor quality of part of the included studies.

Successful Treatment of Near Fatal Cardiogenic Shock Following Toxic Mushroom Ingestion.

Myocardial injury and hemodynamic compromise following toxic mushroom ingestion is rare. Here we present a case of cardiogenic shock after Amanita proxima ingestion, presenting with severe hemodynamic collapse necessitating mechanical circulatory support. Prompt identification, multidisciplinary clinical decision making, and timely treatment resulted in an outstanding complete clinical resolution. (Level of Difficulty: Intermediate.).

Efficacy and safety of Puerarin injection on acute heart failure: A systematic review and meta-analysis.

Objective: This study aimed to assess the adjunctive efficacy and safety of Puerarin injection (PI) on acute heart failure (AHF) based on a systematic review and meta-analysis. Methods: Nine databases were searched from March 1990 to March 2022 to identify randomized controlled trials (RCTs) related to the adjunctive treatment of PI for AHF. The Cochrane collaboration tool was used to assess the risk of bias in the included studies. Meta-analysis and subgroup and sensitivity analyses were conducted by RevMan 5.3 software. The evidence's certainty was evaluated by grading recommendations assessment, development, and evaluation (GRADE) methods. Results: A total of 8 studies were included with a total of 614 patients with AHF. The meta-analysis demonstrated that adjunctive treatment with PI on AHF was superior to conventional medicine alone. It increased the total effective rate (RR = 1.38; 95% CI, 1.22-1.55; p < 0.001) and improved left ventricular ejection fraction [SMD = 0.85; 95% CI (0.62, 1.09); p < 0.001]. Regarding safety, a total of 11.9% (23/194) adverse reactions were observed in the PI group and 9.8% (19/194) adverse reactions in the control group, and there were no significant differences in the incident rate of adverse events between both groups [RR = 1.16; 95% CI (0.66-2.05); p = 0.061]. The outcomes' evidentiary quality was assessed as "moderate." Conclusion: PI had an adjunctive effect on AHF combined with conventional medicine, and it seemed to be safe and more effective than the conventional medical treatment alone for improving the total clinical effective rate and left ventricular ejection fraction. But further well-designed RCTs are required to confirm the efficacy and safety of XBP in treating AHF due to the poor methodological quality of the included RCTs. Systematic Review Registration: [https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=327636], identifier [CRD42022327636].

IV Sodium Ferric Gluconate Complex in Patients Hospitalized Due to Acute Decompensated Heart Failure and Iron Deficiency.

Background: Patients suffering from heart failure (HF) and iron deficiency (ID) have worse outcomes. Treatment with intra-venous (IV) ferric carboxymaltose has been shown to reduce HF rehospitalizations and to improve functional capacity and symptoms in patients with HF and reduced ejection fraction (HFrEF). However, IV ferric carboxymaltose is significantly more expensive than IV sodium ferric gluconate complex (SFGC) limiting its availability to most HF patients around the globe. Methods: A retrospective analysis comparing patients admitted to internal medicine or cardiology departments between January 2013 to December 2018 due to acute decompensated HF (ADHF) and treated with or without IV SFGC on top of standard medical therapy. Results: During the study period, a total of 1863 patients were hospitalized due to ADHF with either HFrEF or HF with preserved ejection fraction (HFpEF). Among them, 840 patients had laboratory evidence of iron deficiency (absolute or functional) and met the inclusion criteria. One hundred twenty-two of them (14.5%) were treated with IV SFGC during the index hospitalization. Patients treated with IV iron were more likely to have history of ischemic heart disease, atrial fibrillation, and chronic kidney disease. The rate of readmissions due to ADHF was similar between the groups at 30 days, 3 months, and 1 year. Conclusion: High risk patient hospitalized to ADHF and treated with IV SFGC showed comparable ADHF readmission rates, compared to those who did not receive iron supplementation.

Effectiveness of Yiqi Fumai lyophilized injection for acute heart failure: Rationale and design of the AUGUST-AHF cohort study.

Introduction: The effect of Yiqi Fumai lyophilized injection (YQFM) on acute heart failure (AHF) patients has been evaluated in a large sample, randomized, controlled trial (AUGUST-AHF RCT study). However, restrictive eligibility criteria from a randomized clinical trial may raise concerns about the generalizability of the results to under-represented groups or complex patients with multimorbidity. Therefore, we intend to conduct the AUGUST-AHF cohort study which aims to assess the effectiveness of YQFM in patients with AHF in a real-world setting and compare the results with AUGUST-AHF RCT study. Methods and analysis: This prospective, multicenter cohort study will be conducted at 50 secondary and tertiary hospitals in China and comprise 1,200 patients with AHF. The participants will be followed for up to at least 180 days. The primary outcome is a composite of 90-day all-cause mortality or readmission for heart failure. The secondary outcomes include length of hospital stay, cardiac-specific death, MACE, NYHA cardiac function classification. Cox proportional-hazards regression models will be used to estimate the association between YQFM use and the primary outcome. The primary analysis will use propensity-score matching methods to balance the differences in baseline variables between treatment cohorts. Ethics and dissemination: Approval for the study has been obtained from the Ethical Committee of Dongzhimen Hospital (approval No. 2022DZMEC-327-02) and registered at ClinicalTrials.gov (NCT05586048). The study results will be published in peer-reviewed journals and presented at scientific conferences.

Valvular Heart Disease Presenting as Sympathetic Crashing Acute Pulmonary Edema (SCAPE) Phenomenon: A Diagnostic and Management Paradigm.

Sympathetic crashing acute pulmonary edema (SCAPE) is an acute decompensated heart failure due to sympathetic overflow. SCAPE is usually triggered by acute insults with an underlying substrate such as long-standing hypertension, chronic heart failure, and valvular heart disease. We present a case of SCAPE in a 91-year-old female due to underlying multivalvular heart disease. Because of severe acute presentation, SCAPE should be identified early, and management should be urgently done to decrease the need for invasive ventilation and prolonged hospitalization.

Real-world experience of feasibility and efficacy of electrical muscle stimulation in elderly patients with acute heart failure: A randomized controlled study.

BACKGROUND: Reduced aerobic capacity and deconditioning contributes to morbidity and mortality in elderly acute heart failure (AHF) patients. Electrical muscle stimulation (EMS) has shown to be a suitable alternative to exercise in AHF. However, feasibility and efficacy are unknown in a real-world setting. METHODS: This is a prospective, open label blinded, randomized, controlled study, investigating feasibility and efficacy of high-intensity versus low-intensity EMS versus controls in elderly AHF patients. Patients and investigators were blinded to the intervention. EMS was offered to > 60 years old AHF patients, initiated during hospitalization and continued at home. Outcome measures included changes in 6-min walking test distance (6-MWTD), functional capacity and quality-of-life at 3 and 6 weeks. RESULTS: Among 97 consecutive AHF patients (78.1 ± 9.4 years, 42.3% females), 60 (61.9%) were eligible for EMS. Of these, 27 provided written informed consent and were randomly assigned to high-intensity (n = 10), low-intensity EMS (n = 9) and controls (n = 8). 13/27 completed the intervention. Main reason for dropouts was intolerance of the overall intervention burden. MACE occurred in 5 and were not associated with the study. EMS groups showed significant improvement of 6-MWTD (controls vs low-intensity p = 0.018) and of independence in daily living (for both p < 0.05). CONCLUSIONS: Changes in 6-MWTD suggest efficacy of EMS. Whereas all tolerated EMS well, the burden of study intervention was too high and resulted in a consent rate of <50% and high dropouts, which limit the interpretability of our data. Less demanding EMS protocols are required to evaluate the full potential of EMS in elderly AHF patients.

Iron Deficiency: A New Target for Patients With Heart Failure.

Iron deficiency (ID) is one of the most frequent comorbidities in patients with heart failure (HF). ID is estimated to be present in up to 50% of outpatients and is a strong independent predictor of HF outcomes. ID has been shown to reduce quality of life, exercise capacity and survival, in both the presence and absence of anemia. The most recent 2016 guidelines recommend starting replacement treatment at ferritin cutoff value <100 mcg/l or between 100 and 299 mcg/l when the transferrin saturation is <20%. Beyond its effect on hemoglobin, iron plays an important role in oxygen transport and in the metabolism of cardiac and skeletal muscles. Mitochondria are the most important sites of iron utilization and energy production. These factors clearly have roles in the diminished exercise capacity in HF. Oral iron administration is usually the first route used for iron repletion in patients. However, the data from the IRONOUT HF study do not support the use of oral iron supplementation in patients with HF and a reduced ejection fraction, because this treatment does not affect peak VO2 (the primary endpoint of the study) or increase serum ferritin levels. The FAIR-HF and CONFIRM-HF studies have shown improvements in symptoms, quality of life and functional capacity in patients with stable, symptomatic, iron-deficient HF after the administration of intravenous iron (i.e., FCM). Moreover, they have shown a decreased risk of first hospitalization for worsening of HF, as later confirmed in a subsequent meta-analysis. In addition, the EFFECT-HF study has shown an improvement in peak oxygen consumption at CPET (a parameter generally considered the gold standard of exercise capacity and a predictor of outcome in HF) in patients randomized to receive ferric carboxymaltose. Finally, the AFFIRM AHF trial evaluating the effects of FCM administration on the outcomes of patients hospitalized for acute HF has found significantly fewer hospital readmissions due to HF among patients treated with FCM rather than placebo.

The influence of integrated healthcare on the nursing effect, negative emotions, and heart failure indicators in acute heart failure patients.

OBJECTIVE: To investigate the effect of integrated healthcare on the nursing of heart failure patients, as well as its influence on the negative emotions and the factors related to heart failure. METHODS: 150 patients with acute heart failure admitted to our hospital were randomly divided into two groups. The patients in the control group underwent routine care, and the patients in the research group were treated with integrated healthcare. The two groups' general information, symptom improvements, six-minute walking distances, emotional conditions, quality of life (MLHFQ scores), N-terminal brain natriuretic peptide (NT-proBNP) levels, mortality rates, rehospitalization rates, and satisfaction rates were compared. RESULTS: The time required for symptom improvement in the research group was shorter than it was in the control group (P<0.001). The patients' six-minute walking distances in the research group were longer than the distances in the control group (P<0.001). There were no differences in the emotional changes between the two groups before the nursing (P>0.05), but after the nursing, the negative emotion scores in the research group were significantly decreased when compared with the control group (P<0.001). The MLHFQ scores and the NT-proBNP levels in the research group were both lower than they were in the control group (P<0.001). No significant differences were observed between the two groups in their mortality or rehospitalization rates (P>0.05). However, the patient satisfaction rates in the research group was higher than they were in the control group (P<0.05). CONCLUSION: As a care plan for patients with acute heart failure, the integrated healthcare plan significantly relieved the patients' anxiety and efficiently improved the patients' quality of life, an indication that integrated healthcare is worth promoting and applying clinically.

Uso de Solución Hipertónica en pacientes con insuficiencia cardiaca aguda como terapia adyuvante a altas dosis de diuréticos / Use of Hypertonic Solution in patients with acute heart failure as adjunctive therapy to high-dose diuretics

Resumen La insuficiencia cardíaca aguda descompensada (ICAD) es una causa común de hospitalización, con repercusiones significativas en los sistemas de salud. El manejo agudo se basa en la reducción de la volemia con diuréticos de asa, sin embargo, un porcentaje de pacientes presenta resistencia o no logra la respuesta clínica esperada con este tratamiento. Una de las medidas que ha comprobado ser efectiva en este contexto, es el uso de solución salina hipertónica (SSH) en conjunto con dosis altas de diuréticos de asa, como medida terapéutica temida por sus posibles repercusiones sobre la función renal y posible sobrecarga de sodio. Objetivos: Determinar si el uso de solución salina hipertónica en pacientes con falla cardiaca aguda e hipervolemia genera un deterioro de la función renal. Determinar la respuesta del Pro-BNP ante el uso de la solución salina hipertónica en pacientes con falla cardiaca aguda como marcador de respuesta terapéutica. Determinar si el uso de solución salina hipertónica aumenta la diuresis sin generar cambios importantes en el sodio. Se muestran datos de pacientes con insuficiencia cardiaca aguda descompensada, que tras no presentar mejoría con altas dosis de diurético de asa en bolo, se les aplicó la solución hipertónica como adyuvante a este tratamiento. Se toma un total de 26 pacientes analizando datos generales clínicos y de laboratorio, se valoran curvas con la respuesta diurética y por parámetros de laboratorio a las 48 y 72 horas. El uso de solución salina hipertónica consigue un aumento de más de un 200% de la diuresis en 24 horas, con un descenso del Pro BNP de más de un 60% a las 48 horas, sin mostrar un cambio importante en los niveles de creatinina, nitrógeno ureico y sodio. Se requirió reposición de potasio en la totalidad de los pacientes. Se concluye que la infusión de furosemida más solución hipertónica es efectiva tanto en disminuir niveles de NT Pro-BNP en los pacientes, como en generar un aumento en el volumen de diuresis. La principal complicación fue la hipokalemia, sin cambios considerables en el valor de sodio, creatinina y nitrógeno ureico séricos.

Abstract Uso de Solución Hipertónica en pacientes con insuficiencia cardiaca aguda como terapia adyuvante a altas dosis de diuréticos Acute decompensated heart failure (AHF) is a common cause of hospitalization, with significant repercussions on health systems. Acute management is based on the reduction of blood volume with loop diuretics; however, a percentage of patients show resistance or do not achieve the expected clinical response with this treatment. One of the measures that has proven to be effective in this context is the use of hypertonic saline (HSS) in conjunction with high doses of loop diuretics, as a therapeutic measure feared due to its possible repercussions on kidney function and possible sodium overload. Objetives: To determine if the use of hypertonic saline in patients with acute heart failure and hypervolemia leads to a deterioration in renal function. To determine the response of Pro-BNP to the use of hypertonic saline in patients with acute heart failure as a marker of therapeutic response. Determine if the use of hypertonic saline increases urine output without causing significant changes in sodium. Data are shown from patients with acute decompensated heart failure, who after not presenting improvement with high doses of bolus loop diuretic, the hypertonic solution was applied as an adjunct to this treatment. A total of 26 patients are taken analyzing general clinical and laboratory data, curves with the diuretic response and by laboratory parameters are evaluated at 48 and 72 hours. The use of hypertonic saline solution achieves an increase of more than 200% in diuresis in 24 hours, with a decrease in Pro BNP of more than 60% at 48 hours, without showing a significant change in creatinine levels, urea nitrogen and sodium. Potassium replacement was required in all patients. It is concluded that the infusion of furosemide plus hypertonic solution is effective both in reducing levels of NT Pro-BNP in patients, and in generating an increase in the volume of diuresis. The main complication was hypokalemia, without significant changes in serum sodium, creatinine, and urea nitrogen.

Development of a Core Outcome Set for the Benefits and Adverse Events of Acute Heart Failure in Clinical Trials of Traditional Chinese Medicine and Western Medicine: A Study Protocol.

Aims: To identify a minimum set of efficacy and adverse events for patients with acute heart failure (AHF) among different stakeholders in clinical trials of traditional Chinese medicine and Western medicine. Methods and Analysis: First, we will develop a preliminary long list of outcomes that includes efficacy and adverse events/reactions via three steps: (i) systematic reviews of efficacy and safety outcomes for clinical trials of AHF; (ii) drugs included in the National Medical Insurance Catalog, the National Essential Medicines Catalog, and the WHO Essential Medicines List will be collected and safety outcomes extracted from the package inserts; and (iii) patients' or caregivers' semi-structured interviews will be carried out to add new viewpoints to the list. Second, after merging outcomes and grouping them under different outcome domains, questionnaires for health professionals and patients will be separately developed. Further, two rounds of Delphi survey for health professionals and a survey for patients and the public will be carried out. Third, different stakeholders will discuss and determine the final core outcome set (COS) for AHF in a consensus meeting. Ethics and Dissemination: The entire project has been approved by the Ethics Committee of the main institution. After the final COS is developed, it will be published and discussed widely in conferences. Clinical Trial Registration: This study is registered with the Core Outcome Measures in Effectiveness Trials database as study 1566 (available at: https://www.cometinitiative.org/Studies/Details/1566).

Rationale and design of the AUGUST-AHF Study.

AIMS: We aim to assess the effect of a lyophilized herbal injection on 90 day mortality and readmission rates in patients with acute heart failure (AHF). METHODS AND RESULTS: The AUGUST-AHF study is a multicentre, randomized, double-blind, placebo-controlled trial enrolling 1270 hospitalized patients for AHF. Patients are randomized to receive YiqiFumai lyophilized injection (5.2 g/day) or placebo for 10 days, in addition to standard therapy, using a 1:1 ratio via an interactive web response system. The primary endpoint is the 90 day all-cause mortality or AHF readmission rates. Secondary endpoints include 180 day all-cause mortality or heart failure readmission rates, length of hospital stay for the indexed AHF, 90 day cardiac-specific mortality rate, occurrence of worsening heart failure through Day 10, changes in the Minnesota Living with Heart Failure Quality of Life scale score through Day 180, and 90 day major adverse cardiac events. Additional secondary endpoints include change in dyspnoea via visual analogue scale (VAS) and Likert 7-point comparator scale, N terminal pro-B-type natriuretic peptide value and New York Heart Association functional class, and the total amount of diuretics for the indexed AHF hospitalization. Study recruitment is expected to be completed by March 2021, and follow-up will end in September 2021. In an optional sub-study, patients will be followed up for 3 years. CONCLUSIONS: To our best knowledge, AUGUST-AHF is the first study assessing the efficacy of a Chinese herbal injection in patients with AHF. The results will be valuable to guide clinicians in using YiqiFumai lyophilized injection, which was included in the latest Chinese Health Insurance Catalog.

Outpatient treatment of worsening heart failure with intravenous and subcutaneous diuretics: a systematic review of the literature.

AIMS: In the coming decade, heart failure (HF) represents a major global healthcare challenge due to an ageing population and rising prevalence combined with scarcity of medical resources and increasing healthcare costs. A transitional care strategy within the period of clinical worsening of HF before hospitalization may offer a solution to prevent hospitalization. The outpatient treatment of worsening HF with intravenous or subcutaneous diuretics as an alternative strategy for hospitalization has been described in the literature. METHODS AND RESULTS: In this systematic review, the available evidence for the efficacy and safety of outpatient treatment with intravenous or subcutaneous diuretics of patients with worsening HF is analysed. A search was performed in the electronic databases MEDLINE and EMBASE. Of the 11 included studies 10 were single-centre, using non-randomized, observational registries of treatment with intravenous or subcutaneous diuretics for patients with worsening HF with highly variable selection criteria, baseline characteristics, and treatment design. One study was a randomized study comparing subcutaneous furosemide with intravenous furosemide. In a total of 984 unique individual patients treated in the reviewed studies, only a few adverse events were reported. Re-hospitalization rates for HF at 30 and 180 days were 28 and 46%, respectively. All-cause re-hospitalization rates at 30 and 60 days were 18-37 and 22%, respectively. The highest HF re-hospitalization was 52% in 30 days in the subcutaneous diuretic group and 42% in 30 days in the intravenous diuretic group. CONCLUSIONS: The reviewed studies present practice-based results of treatment of patients with worsening HF with intravenous or subcutaneous diuretics in an outpatient HF care unit and report that it is effective by relieving symptoms with a low risk of adverse events. The studies do not provide satisfactory evidence for reduction in rates of re-hospitalization or improvement in mortality or quality of life. The conclusions drawn from these studies are limited by the quality of the individual studies. Prospective randomized studies are needed to determine the safety and effectiveness of outpatient intravenous or subcutaneous diuretic treatment for patient with worsening HF.

Synergistic effect of Aconiti Lateralis Radix Praeparata water-soluble alkaloids and Ginseng Radix et Rhizoma total ginsenosides compatibility on acute heart failure rats.

The aim of this study was to investigate the synergistic effect and underlying mechanism of compatibility of Aconiti Lateralis Radix Praeparata water-soluble alkaloids (FWA) and Ginseng Radix et Rhizoma total ginsenosides (RTG) on propafenone hydrochloride induced acute heart failure (AHF) rats. Firstly, hemodynamics and serum biochemical indexes were measured to observe the therapeutic effect of FWA, RTG and their compatibility on AHF rats. Non-target serum metabolomics and multicomponent pharmacokinetic experiments were then performed to reveal the mechanism from the two aspects of body reaction and drug behavior in vivo. Data showed the haemodynamics indexes (maximum change rate of left ventricular pressure, heart rate) and neuroendocrine cytokines (TNF-α and Nt-proBNP) levels in rats treated by compatibility of FWA and RTG were improved more significantly than that treated by single drug. Through metabolomics analysis, six metabolites, including L-pipecolic acid, L-arginine, uric acid, N-benzoylglycine, sphingosine-1-phosphate and phosphatidylinositol lyso 16:0, were selected and identified as the potential biomarkers of the synergistic effect. Furthermore, lysine degradation, arginine and proline metabolism, purine metabolism, sphingolipid metabolism, etc. were the differential pathways involved. The results of pharmacokinetics showed Cmax, AUClast and t1/2 of the four components (uracil, salsolinol, guanosine, higenamine) of FWA in compatibility group were obviously higher than that in single drug group, which indicated the absorption and bioavailability of these alkaloids were increased, and the residence time was prolonged after FWA combined with RTG. In conclusion, the therapeutic effect of FWA-RTG on AHF rats was enhanced and that might because the compatibility of FWA-RTG affected the process of some metabolites in AHF rats, and pharmacokinetic behavior of components in FWA was obviously influenced after co-administered with RTG.

Rationale and design of the AFFIRM-AHF trial: a randomised, double-blind, placebo-controlled trial comparing the effect of intravenous ferric carboxymaltose on hospitalisations and mortality in iron-deficient patients admitted for acute heart failure.

AIMS: Iron deficiency (ID) is a common co-morbidity in heart failure (HF), associated with impaired functional capacity, poor quality of life and increased morbidity and mortality. Treatment with intravenous (i.v.) ferric carboxymaltose (FCM) has shown improvements in functional capacity, symptoms and quality of life in stable HF patients with reduced ejection fraction. The effect of i.v. iron supplementation on morbidity and mortality in patients hospitalised for acute HF (AHF) and who have ID has yet to be established. The objective of the present article is to present the rationale and design of the AFFIRM-AHF trial (ClinicalTrials.gov NCT02937454) which will investigate the effect of i.v. FCM (vs. placebo) on recurrent HF hospitalisations and cardiovascular (CV) mortality in iron-deficient patients hospitalised for AHF. METHODS: AFFIRM-AHF is a multicentre, randomised (1:1), double-blind, placebo-controlled trial which recruited 1100 patients hospitalised for AHF and who had iron deficiency ID defined as serum ferritin <100 ng/mL or 100-299 ng/mL if transferrin saturation <20%. Eligible patients were randomised (1:1) to either i.v. FCM or placebo and received the first dose of study treatment just prior to discharge for the index hospitalisation. Patients will be followed for 52 weeks. The primary outcome is the composite of recurrent HF hospitalisations and CV mortality. The main secondary outcomes include the composite of recurrent CV hospitalisations and CV mortality, recurrent HF hospitalisations and safety-related outcomes. CONCLUSION: The AFFIRM-AHF trial will evaluate, compared to placebo, the effect of i.v. FCM on morbidity and mortality in iron-deficient patients hospitalised for AHF.