AHF Patients Research Articles

Inferior vena CAVA and lung ultraSound-guided therapy in acute heart failure: A randomized pilot study (CAVAL US-AHF study)

The optimal assessment of systemic and lung decongestion during acute heart failure is not clearly defined. We evaluated whether inferior vena cava (IVC) and pulmonary ultrasound (CAVAL US) guided therapy is superior to standard care in reducing subclinical congestion at discharge in patients with AHF. CAVAL US-AHF was an investigator-initiated, single-center, single-blind, randomized controlled trial. A daily quantitative ultrasound protocol using the 8-zone method was used and treatment was adjusted according to an algorithm. The primary endpoint was the presence of more than 5 B-lines and/or an increase in IVC diameter and collapsibility at discharge. And secondary endpoint exploratory outcome was the composite of readmission for HF, unplanned visit for worsening HF or death at 90 days RESULTS: Sixty patients were randomized to CAVAL US (n = 30) or control (n = 30). The primary endpoint was achieved in 4 patients (13.3%) in the CAVAL US group and 20 patients (66.6%) in the control group (P < .001). A significant reduction in HF readmission, unplanned visit for worsening HF or death at 90 days was seen in the CAVAL US group (13.3% vs 36.7%; log rank P = .038). Other endpoints such as NT-proBNP reduction at discharge showed a nonstatistically significant reduction in the CAVAL US group (48% IQR 27-67 vs 37% -3-59; P = .09). Safety outcomes were similar in both groups. IVC and lung ultrasound-guided therapy in AHF patients significantly reduced subclinical congestion at discharge. CAVAL US-AHF provides preliminary evidence for the potential use of a simple technique to guide decongestive therapy during hospitalization for AHF, which may reduce the composite outcome at 90 days.

Rationale and design of the French Observatory of Acute Heart Failure (OFICA2)

BackgroundAcute heart failure (AHF) is a leading cause of hospitalization and mortality – especially in patients aged≥65 years in high-income countries – and represents a high healthcare burden. In the past decade, the epidemiology and management of heart failure (HF) has changed, with the emergence of new medical and interventional therapeutics, but up-to-date real-life data are scarce. AimsThe main objectives are to describe baseline characteristics (with an emphasis on lifestyle, cognitive status, HF knowledge and treatment adherence), management, and in-hospital and mid-term outcomes of AHF patients in France. Secondary objectives are to investigate determinants of prognosis, modalities of treatment and follow-up, and identify gaps between guidelines and real-life management. MethodsOFICA2 is a prospective multicentre observational survey that enrolled 1513 patients hospitalized for AHF in 80 participating centres in France during March and April 2021. The diagnosis of AHF was made according to the European Society of Cardiology guidelines definition. Inclusion criteria were age≥18years, health coverage and consent to participate. Detailed information was collected prospectively starting at admission. Thanks to direct linking with the French National Health Database, the anteriority up to 2years before inclusion, as well as a 3-year follow-up is specified for each patient and includes individual information on death, hospital admissions, major clinical events, drug delivery and use of reimbursed health resources. ConclusionThis cohort provides a representative snapshot on contemporary AHF, with a particular focus on self-care determinants, and will improve knowledge about AHF presentation, management and outcomes.

Association Between Serum Albumin and the Length of Hospital Stay Among Patients With Acute Heart Failure.

Introduction: Albumin plays a vital role in improving osmotic pressure and hemodynamics. A lower serum albumin level may cause pulmonary congestion and edema and contribute to myocardial dysfunction, diuresis resistance, and fluid retention in acute heart failure. Hypothesis: We hypothesized that AHF patients with normal serum albumin have shorter hospital stays. Methods: Using Electronic Medical Records, patients admitted from May 2020 through May 2021 aged >18, ICD-10, and positive Framingham Heart Failure Diagnostic Criteria were included. We excluded patients without albumin records and eGFRs less than 30mL/min/1.73m2. Prolonged hospitalization was defined as >8days of hospitalization. Results: During index emergency department visits, patients were symptomatic (New York Heart Association), aged median of 70years (Interquartile range (IQR) 18), 59% (n = 103) were male, predominantly White (73%, n = 128), and had a high Charleston Comorbidity index score [5, IQR (4-7)]. Nearly one-fourth (23%, n = 41) of the patients had <3.5g/dL albumin levels. The median length of hospital stay was eight days (IQR of 11). Comparing differences between lengths of hospital stays (<8 vs. >8 days), there was different serum albumin (3.9 + 0.48 vs. 3.6 + 0.53, p < .001) and left ventricular ejection fraction (45% (range 26-63) versus 30% (range 24-48), p = .004). An increased serum albumin decreased prolonged hospitalization (odds ratio (OR), 0.28; 95% confidence interval (CI), 0.14-0.55, p = <0.001). Patients in the lower albumin group had higher NT-proBNP (median: 8521 (range 2025-9134) versus 5147 (range 2966-14,795) pg/ml, p = .007) and delay in administering intravenous diuretics (391 (167-964) minutes versus 271 (range 157-533) minutes, p = .02). Conclusion: Hypoalbuminemia is strongly associated with prolonged hospitalization. Timely and effective diuretic therapy may reduce hospital stay durations, particularly with albumin supplementation.

Representativeness of the PIONEER-HF and PARAGLIDE-HF in patients hospitalized with acute heart failure.

The PIONEER-HF and PARAGLIDE-HF trials aimed to determine the efficacy and safety of the in-hospital initiation of sacubitril/valsartan in patients hospitalized for AHF. However, whether the inclusion and exclusion criteria of the trials apply to patients encountered in real-world routine care is unclear. This study aimed to investigate the applicability of the PIONEER-HF and PARAGLIDE-HF trials to real-world AHF patients. We identified 28293 AHF hospitalized patients between August 2008 to August 2017 from the Chang Gung Research Database and classified them into four groups based on left ventricular ejection fraction (LVEF) and trial criteria. Cox proportional hazards models were used to compare the risk of HF hospitalization and cardiovascular (CV) death. We defined PIONEER-HF eligible (n=3683) and non-eligible (n=3502) patients with an LVEF ≤40%, and PARAGLIDE-HF eligible (n=5191) and non-eligible (n=5832) patients with an LVEF >40%. Over a mean follow-up of 3.5years, the PIONEER-HF non-eligible and eligible groups exhibited similar rates of HF hospitalization and CV death (41.1% vs. 41.8%, adjusted hazard ratio [aHR]: 0.95; 95% CI: 0.88-1.04). No significant difference was found in the composite outcome between PARAGLIDE-HF non-eligible and eligible groups (36.7% vs. 38.6%; aHR: 0.97; 95% CI: 0.90-1.04). Using trial criteria, only 31.3% of AHF patients were eligible for sacubitril-valsartan. Yet, non-eligible patients demonstrated similar outcomes to eligible patients, indicating a need for further evaluation of sacubitril-valsartan benefits in non-eligible AHF patients.

Predischarge Peak Atrial Longitudinal Strain and Plasma N-terminal Pro-hormone Brain Natriuretic Peptide as a Predictor of Short-term Rehospitalization and Cardiovascular Mortality in Patients with Acute Heart Failure.

The postacute heart failure (AHF) rehospitalization rate is attributed to persistent hemodynamic congestion despite clinical improvement. Peak atrial longitudinal strain (PALS), utilizing speckle tracking echocardiography technology, shows potential in post-AHF prognosis. Meanwhile, N-terminal pro-hormone brain natriuretic peptide (NT-proBNP) remains a known biomarker of intracardiac congestion. This study aimed to determine the relationship between predischarge PALS and NT-proBNP as predictors of major adverse cardiac event (MACE) in patients after AHF hospitalization. This study is a prospective cohort study, conducted in Prof. Dr. I G.N.G Ngoerah Hospital, Bali, Indonesia. The study included hospitalized AHF patients, collecting demographic data, comorbidities, therapies, and echocardiographic measures before discharge. Predischarge PALS and NT-proBNP were taken within 24 h before discharge. The main outcome was MACE, defined as rehospitalization and cardiovascular mortality within 90 days. Comparative statistical analyses was done using independent t-test for continuous variables (Mann-Whitney U test for variables with abnormal distribution) and Chi-squared tests. Receiver operating characteristic (ROC) used in determining optimal threshold values of predischarge PALS and NT-proBNP as a predictor of MACE. Kaplan-Meier curves were employed to gauge event-free survival differences between these cohorts. Then, independent Cox regression was used to identify the predictors of MACE. The study enrolled 67 patients with varying ejection fraction (EF) (16 - heart failure with preserved ejection fraction, 10 - heart failure with mildly reduced ejection fraction, and 41 - heart failure with reduced ejection fraction; mean age: 56.88 ± 14.57 years). Over the 90-day follow-up, 21 patients (31.3%) encountered MACE. Both PALS (area under the curve [AUC] 0.816) and NT-proBNP (AUC 0.856) before discharge served as predictors of MACE. There was no significant AUC difference between ROC curves (area difference: 0.039, P = 0.553). The regression model highlighted that PALS and NT-proBNP level before discharge acted as independent predictors of MACE, irrespective of EF, average E/e', or estimated predischarge pulmonary capillary wedge pressure. Predischarge PALS is comparable to NT-proBNP levels as independent predictors of short-term MACE after AHF hospitalization.

Imbalance of iron needs and supply in patients with acute and chronic heart failure

Abstract Background Iron deficiency (ID) is frequent in patients with chronic and acute heart failure (CHF, AHF) associated with morbidity and mortality. ID can be absolute, defined as depleted iron stores (also named true ID), or functional describing hypoferremia despite adequate iron stores as a result of inflammation-related reduced iron mobilization and restriction in mononuclear cells. Empty iron stores can also be found simultaneously to inflammation-related reduced iron mobilization (combined ID). Purpose We aimed to better characterize ID and iron homeostasis in HF patients applying different biomarkers and to evaluate the accuracy of current ID definition by the ESC to indicate actual tissue iron needs and supply. Methods We performed a retrospective cohort study including 277 AHF and 476 CHF patients treated between 02/2021–05/2022 at the Medical University of Innsbruck. Results AHF patients had higher iron needs and lower iron supply than CHF patients, reflected by increased soluble transferrin receptor (sTfR) and sTfR-Ferritin (sTfR-F) index, and lower ferritin, serum iron, transferrin saturation (TfS), hepcidin and reticulocyte hemoglobin (Ret-Hb). Only 28.0% of CHF and 81.4% of AHF patients with absolute ID as well as 10.5% of CHF and 50.0% of AHF patients with combined ID based on the current ESC definition presented with an elevated sTfR-F index (&amp;gt;2.0 without and &amp;gt;3.2 with inflammation) and/or reduced Ret-Hb (&amp;lt;28pg), being indicative for tissue iron needs. Suppressed hepcidin expression (≤8.6ng/mL) as early marker of iron depletion was found in 80% of CHF and 91% of AHF patients with absolute ID and only in 19% of CHF and 32% of AHF patients with combined ID based on the current ESC definition. When breaking down the ID definition into ferritin and TfS, in AHF an elevated sTfR-F index was found in patients with inflammation and associated with lower ferritin (&amp;lt;200 ng/mL), while a reduced Ret-Hb was primarily found in patients with inflammation, TfS &amp;lt;20% and ferritin &amp;lt;100 ng/mL. In CHF an elevated sTfR-F index and a reduced Ret-Hb were primarily present in patients with ferritin &amp;lt;30 ng/mL and TfS &amp;lt;20% as well as in patients with inflammation, TfS &amp;lt;20% and ferritin &amp;lt;100 ng/mL. (Figure 1) Specificity for defining true ID based on iron needs was increased when including inflammation for defining true ID and reducing the upper limit of ferritin for defining true ID in the setting of inflammation (Figure 2). Conclusion A substantial proportion of patients with ID defined by the current ESC definition, had normal tissue iron supply with no increased tissue iron needs. In accordance with previous studies, results from our study suggest that the current ESC definition might overestimate true ID especially in CHF. A more accurate definition of ID may help to identify those patients with AHF and CHF who truly benefit from intravenous iron supplementation.

Disproportionate MR and 5-year mortality following acute heart failure hospitalisation

Abstract Background The clinical implications of disproportionate mitral regurgitation (DispMR) is contentious and uncertainty remains if this cohort of patients benefit from intervention. Its prognostic significance in acute heart failure remains incompletely investigated. Purpose To examine whether DispMR, defined by the ratio of the effective regurgitant orifice area (ERO)/LVEDV &amp;gt;0.14mm2/ml, is an independent predictor of long-term mortality following hospitalisation for AHF. Methods 418 consecutive AHF patients were recruited and followed up for the primary outcome of all-cause, 5-year mortality. A key secondary outcome was cardiovascular (CV) death. Patients were recruited if they displayed signs and symptoms of AHF, had point-of-care brain-natriuretic peptide &amp;gt;100pg/ml and had evidence of AHF on comprehensive bedside transthoracic echocardiography. 30 variables encompassing age, gender, BMI, a history of COPD, CKD, hypertension, diabetes, previous CVA, CAD, AF on admission ECG, admission systolic BP, NYHA classification, heart rate, Na, BNP, urea, anaemia, LA size, RA size, TR severity, lateral E/e’ &amp;gt;14, RV diastolic area, TAPSE, SPAP, LVEF phenotype, a loop diuretic, MRA, beta-blocker, ARB/ACE-I, CCB or statin prescribed on discharge were included. Multivariate Cox-proportional hazard models were constructed to test for an independent prognostic role of DispMR. Missing outcome data was right-censored. Results 313/418 (74.8%) displayed secondary MR and had quantifiable ERO and LVEDV (median age 81, 53.4% male) and were included in analysis. 217/313 (66.5%) displayed DispMR. Kaplan-Meier curve analysis revealed worse all-cause mortality in DispMR vs. proportionate MR (HR 1.72 95% CI 1.31-2.27 [p&amp;lt;0.001]). On multivariable analysis DispMR was independently associated with all-cause mortality (HR 1.77 (95% CI 1.26-2.51 [p=0.0012]). 284/313 (90.7%) had CV mortality data available. DispMR was associated with increased risk of 5-year, unadjusted, CV mortality compared to proportionate MR (HR 1.72 95% CI 1.31-2.27 [p&amp;lt;0.001]). These effects were present across all ejection fraction phenotypes. Conclusions Among patients with quantifiable MR in AHF, the presence of DispMR was independently associated with long-term outcome. These results suggest assessment of MR within the context of LV volumes can identify patients at increased risk and should have implications for future guidelines.

Hemoglobin to red cell distribution width ratio: A predictor of clinical outcome and diuretic response in patients with acute heart failure

BackgroundHemoglobin to Red Cell Distribution Width Ratio (HRR) is a novel inflammatory marker in the prognostic assessment of tumors. Nevertheless, its focus on the cardiovascular field is relatively limited, particularly regarding its correlation with diuretic responses and clinical outcomes. MethodsThis is a secondary analysis of the Renal Optimization Strategies Evaluation (ROSE AHF) clinical trial. The outcomes of interest included all-cause death, rehospitalization and diuretic responses. Multivariable Cox proportional hazard regression and linear regression models were performed, respectively. Prognostic outcomes and diuretic response were further evaluated in ejection fraction (EF) subgroups (preserved EF ≥ 50% and reduced EF<50%). ResultsA total of 351 patients were included in the present study and further categorized according to HRR median (0.7131) value at admission: low HRR group (n = 176) and high HRR group (n = 175). High HRR were found to be independently associated with decreased risk of all-cause death (HR = 0.51; 95% CI,0.30–0.87, P = 0.013), reduced risk of developing all-caused death or rehospitalization (HR = 0.62; 95% CI,0.39–0.98, P = 0.039). Furthermore, high HRR indicated lower cumulative urine output (OR: -992.33, P = 0.004) and less weight loss (OR: 3.08, P < 0.001) within 72 h after diuresis. Subgroup analysis revealed no significant interaction effect between EF and HRR in prognostic impact or diuretic responses, and HRR was negatively correlated with plasma volume. ConclusionHigh HRR demonstrated a lower risk of developing adverse clinical outcomes and a poorer diuretic response that might be due to less volume overload in AHF patients.

A comprehensive review of acute cardio-renal syndrome: need for novel biomarkers.

Cardiorenal syndrome represents a wide-spectrum disorder involving the heart and kidneys as the primary affected organs. India has an increasingly high burden of acute CRS, coinciding with the rise in global statistics. Up to 2022, approximately 46.1% of all cardiorenal patients have been diagnosed with acute CRS in India. Acute CRS involves a sudden deterioration of kidney functionalities, referred to as acute kidney injury (AKI) in acute heart failure patients. The pathophysiology of CRS involves hyperactivation of the sympathetic nervous system (SNS) and the renin-angiotensin-aldosterone system (RAAS) following acute myocardial stress. The pathological phenotype of acute CRS is associated with perturbed inflammatory, cellular, and neurohormonal markers in circulation. These complications increase the risk of mortality in clinically diagnosed acute CRS patients, making it a worldwide healthcare burden. Hence, effective diagnosis and early prevention are crucial to prevent the progression of CRS in AHF patients. Present biomarkers, such as serum creatinine (sCr), cystatin C (CysC), glomerular filtration rate (GFR), blood urea nitrogen (BUN), serum and/or urine neutrophil gelatinase-associated lipocalin (NGAL), B-type natriuretic peptide (BNP), and NT-proBNP, are clinically used to diagnose AKI stages in CRS patients but are limitedly sensitive to the early detection of the pathology. Therefore, the need for protein biomarkers is emerging for early intervention in CRS progression. Here, we summarized the cardio-renal nexus in acute CRS, with an emphasis on the present clinicopathological biomarkers and their limitations. The objective of this review is to highlight the need for novel proteomic biomarkers that will curb the burgeoning concern and direct future research trials.

P243 EXTRACORPOREAL CONTINUOUS VENO–VENOUS ULTRAFILTRATION IN PATIENTS WITH ACUTE HEART FAILURE REFRACTORY TO DIURETIC THERAPY: A SINGLE–CENTER PILOT EXPERIENCE

Abstract Introduction Congestive Acute Heart Failure (C–AHF) is characterized by extracellular fluid overload. Extensive use of loop diuretics may induce worsening renal function, electrolyte imbalance, symptomatic hypotension and diuretic resistance. Extracorporeal veno–venous ultrafiltration (UF) may represent a useful adjunctive therapy. Despite a few randomized clinical trials have been carried out, the results are controversial; aim of this study is to describe our pilot experience using UF. Methods We enrolled consecutive patients with C–AHF refractory to diuretic therapy treated with UF from January to December 2022; patients affected by concomitant acute coronary syndrome were excluded. UF was delivered using a modern device specifically designed for fluid removal in C–AHF patients through slow continuous UF (Fig.1). According to our protocol, the initial UF rate was based on baseline systolic arterial pressure (250cc/h if&amp;gt;120mmHg, 100–120cc/h if 100–120mmHg and &amp;lt;100cc/h if&amp;lt;100mmHg; contra–indicated if&amp;lt;90mmHg). Laboratories values, urinary output and fluid balance were monitored at baseline, after 6 hours (T6) and when UF was stopped (T0). Variables are expressed as medians with 25p–75p. Results Seven patients were enrolled in the study (5M;2F); in each a femoral central venous catheter (20cm/14G) was placed to perform UF. A standard anticoagulation regimen based on UFH bolus + infusion was adopted aiming to an ACT of 180–220. Median age and LVEF were respectively 40[20–50] and 79[73–85]; 3 patients were diabetics, 2 smokers and 4 hypertensive. Median rate of hospitalization in the previous 12 months was 1 [0–2]; domiciliary dosage of furosemide was 75mg [50–125]. Baseline, T6h and T0 creatinine values were respectively 1.2 [1.1–2], 1.3 [1.1–1.8] and 1.4 [1.1–1.9]. Heart rate and blood pressure were stable during the treatment. UF parameters in the patients of the study are summarized in Tab.1; congestion was resolved or improved in 6/7 patients, no severe complication (bleeding, AKI, death) occurred while 1 premature filter clot is reported. Conclusions Our initial experience with UF is promising. Modern heart failure specific devices appear safe, easy to use and require only minimal training. Compared to extensive i.v. diuretic use, predictable fluid removal through UF may be beneficial as it is characterized by higher excretion of sodium, limited neuro–hormonal activation, enhanced spontaneous diuresis and restoration of diuretic response.

Salivary lipid mediators: Key indexes of inflammation regulation in heart failure disease.

Cardiovascular diseases (CVDs) are the leading cause of premature death and disability in humans and their incidence continues to increase. Oxidative stress and inflammation have been recognized as key pathophysiological factors in cardiovascular events. The targeted modulation of the endogenous mechanisms of inflammation, rather than its simple suppression, will become key in treating chronic inflammatory diseases. A comprehensive characterization of the signalling molecules involved in inflammation, such as endogenous lipid mediators, is thus needed. Here, we propose a powerful MS-based platform for the simultaneous quantitation of sixty salivary lipid mediators in CVD samples. Saliva, which represents a non-invasive and painless alternative to blood, was collected from patients suffering from acute and chronic heart failure (AHF and CHF, respectively), obesity and hypertension. Of all the patients, those with AHF and hypertension showed higher levels of isoprostanoids, which are key indexes of oxidant insult. Compared to the obese population, AHF patients showed lower levels (p<0.02) of antioxidant omega-3 fatty acids, in line with the "malnutrition-inflammation complex syndrome" typical of HF patients. At hospital admission, AHF patients showed significantly higher levels (p<0.001) of omega-3 DPA and lower levels (p<0.04) of lipoxin B4 than CHF patients, suggesting a lipid rearrangement typical of the failing heart during acute decompensation. If confirmed, our results highlight the potential use of lipid mediators as predictive markers of re-acutisation episodes, thus providing opportunities for preventive intervention and a reduction in hospitalizations.

Effect of estimated plasma volume status and left atrial diameter on prognosis of patients with acute heart failure.

Acute heart failure (AHF) is a frequent cardiovascular emergency presenting with high mortality as well as readmission rates. The aim was to investigate the predictive value of estimated plasma volume status (ePVs) and left atrial diameter (LAD) for the prognosis of patients with AHF. Clinical profiles were collected from 259 cases of AHF patients at the Affiliated Hospital of Putian University between September 2019 and October 2021. Six patients lost follow-up, resulting in 253 patients enrolled. Cardiogenic death and heart failure readmission during follow-up were defined as major cardiovascular events (MACE) group, other patients were defined as Non-MACE group. Apart from age, no significant differences were found between the two groups in demographics and comorbidities. The comparison between the two groups was statistically significant in terms of ePVs, LAD, and N-terminal-pro B-type natriuretic peptide (Nt-pro-BNP). On binary logistic regression analysis, ePVs (OR = 2.061, 95% CI 1.322∼3.214, P = 0.001), LAD (OR = 1.054, 95% CI 1.012∼1.098, P = 0.011), and Nt-pro-bnp (OR = 1.006, 95% CI 1.003∼1.010, P = 0.036) as predicting factors for MACE. Kaplan-Meier analysis indicated that the risk for cardiogenic death increasing with ePVs (p < 0.05). Estimated plasma volume status and LADs have some predictive value in assessing cardiogenic death and heart failure readmission in patients with AHF.

Abstract 9486: miR-425/CFL2 Regulates Natriuretic Peptides Expression in Human CVD

Introduction: Previously, miR-425 have been implicated in the inhibition of the cardiac natriuretic peptide (NP) ANP gene expression with their role on BNP undefined. The mechanism by which miR-425 modulates NP expression remains to be explored. In heart failure (HF), adrenergic and neurohormone pathways are aberrantly activated. Our goal was to investigate the role of miR-425 and its downstream target Cofilin 2 (CFL2) on ANP and BNP expression in human CV disease (CVD). Hypothesis: We hypothesized miR-425, via CFL2, supresses NPs expression in vitro. MiR-425, CFL2 and NP levels were also determined in CVD patients. Methods: In vitro, human cardiomyocytes (HCM) were treated with vehicle (Veh), catecholamine isoproterenol (ISO) and cytokine endothelin (ET), miR-425 mimic. Cells were transfected with CFL2 plasmid or CFL2 siRNA. Normal (NM, n=100), Hypertension (HTN, n=30) and Acute HF (AHF, n=74) cohorts were studied. A confirmatory cohort was recruited. Plasma NT-proBNP, miR-425 were measured. In left ventricles (LV) from NM or HF (n=5 each), NP, CFL2 and miR-425 expression were assessed. Data expressed as means±SEM. * p&lt;0.05 vs NM or Veh. Results: In vitro in HCM, treatment with ISO or ET in HCM reduced miR-425 and elevated NP mRNA levels. Furthermore, miR-425 mimic reduced Nppa (Veh: 1.0±0.03, mimic: 0.7±0.02*) and Nppb levels (Veh: 1.0±0.03, mimic: 0.5±0.01*). We showed that a top predicted target of miR-425, CFL2, was also reduced by the mimic. Further, NP mRNA was elevated by CFL2 overexpression and reduced by the knockdown of CFL2. In humans, MiR-425 was lower in HTN and AHF patients (NM: 0.15±0.03, HTN: 0.03±0.005*, HF: 0.01±0.003*) than NM. MiR-425 negatively correlates with NT-proBNP in NM and AHF cohorts. Downregulation of miR-425 was validated in a second AHF cohort. Similarly, in HF LV tissues, miR-425 (NM: 2.5±0.5, HF: 1.0±0.5*) was lower than NM group, while CFL2 and NP gene and protein expression were increased. Conclusion: In vitro, cardiac stress hormones downregulate miR-425 and increase NP gene expression, potentially through a novel target, CFL2. In CVD patients, miR-425 is lower, accompanied by an elevation of CFL2 and NP. Our findings implicate the pathway of stress hormones/miR-425/CFL2/NP production in CVD.

Impact of levosimendan on efficacy and renal function in acute heart failure according to renal function: A perspective, multi-center, real-world registry

Acute heart failure (AHF) is associated with high mortality. Levosimendan, an inodilator, has proved to increase cardiac output and exert renoprotective effect in AHF. Our aim was to investigate the efficacy and renoprotective effects of levosimendan in patients with AHF and different renal function. This is a prospective, observational, multi-center registry. Patients admitted with AHF between June 2020 and May 2022 and treated with levosimendan during the hospital stay were included. Baseline characteristics, laboratory tests, electrocardiogram (ECG), chest X-ray, echocardiography, and treatment were collected. A 5-point Likert scale was used to document patients' baseline dyspnea. The estimated glomerular filtration rate (eGFR) was calculated by means of the Modification of Diet in Renal Disease equation. After levosimendan infusion, patients underwent assessment of degree of dyspnea, and levels of brain-type natriuretic peptide (BNP) /N-terminal pro-BNP (NT-pro BNP), and eGFR repeatedly. Among 789 AHF patients who received levosimendan treatment in this study, 33.0 % were female, mean age was 64.9 ± 16.8 years, and mean eGFR was 72.6 ± 32.5 ml/min/m2. The mean score of dyspnea was 3.0 ± 1.0 using 5-point Likert scale before levosimendan infusion. Dyspnea improved in 68.7% patients at 6h after infusion of levosimendan, and in 79.5% at 24 h. Lower eGFR was associated with lower efficacy rate after 6h infusion (71.7, 70.7, 65.2, and 66.0%, respectively) and after 24 h infusion (80.5, 81.4, 76.2, and 77.8%, respectively). The levels of BNP or NT-pro BNP were also decreased after levosimendan treatment, and in each eGFR category. Levels of eGFR increased from baseline (72.6 ± 32.5 ml/min/m2) to 12-24h (73.8 ± 33.5 ml/min/m2) and 24-72h (75.0 ± 33.4 ml/min/m2) after starting treatment (p < 0.001). However, the eGFR levels increased only in patients with eGFR lower than 90.0 ml/min/m2. In AHF patients who received levosimendan, degree of dyspnea and levels of BNP or NT-pro BNP were significantly improved, especially in patients with higher eGFR levels. However, levosimendan infusion increase eGFR only in AHF patients with renal dysfunction.

Which parameter of right ventricular function predicts outcome in acute heart failure

Abstract Aims RV systolic dysfunction is being recognised as significant prognostic marker of poor outcome in acute heart failure. We aimed to characterise the predictive capacity of RV systolic function on long term outcomes in those hospitalised in AHF. Methods 418 consecutive AHF patients presenting over 12 months were prospectively recruited and underwent bed-side echocardiography within 24 hours of recruitment. 8 parameters of RV systolic function were assessed in predicting 2-year mortality by identifying the sensitivity and specificity associated with the maximum Youden Index. These cut-offs were used as binary determinants of outcome in unadjusted Kaplan-Meier analysis. Results 7/8 binary assessments of RV systolic dysfunction were significantly predictive of 2 year outcome, including the tricuspid annulus systolic plane excursion (TAPSE) ≤1.6cm, RV fractional area change (RVFAC) ≤38.2%, peak systolic and end systolic RV inferior wall global longitudinal strain of &amp;gt;−18.6% and &amp;gt;−18%, inferior free wall average strain rate &amp;gt;−1.8 s–1, a 2D ellipsoid model of RVEF &amp;lt;46.9% and the ratio of the TAPSE to systolic pulmonary artery pressure &amp;lt;0.0268 cm/mmHg (all p&amp;lt;0.02). Crude hazard ratios ranged from 1.50–2.13. Only the RV tissue doppler imaging S wave velocity ≤0.09m/s could not delineate those at risk of poor outcome (p=0.17). Discussion A constellation of RV systolic assessment could effectively delineate those at risk of poor outcome following hospitalisation for AHF. The cut-offs identified were broadly similar to those from the ESC guidelines on RV chamber assessment. Only the S wave velocity from tissue doppler imaging was not predictive. This may be due to more angle dependency in measurements alongside the impact of loading conditions in acute heart failure. RV dysfunction should remain a serious focus of attention from acute physicians and echosonographers. Funding Acknowledgement Type of funding sources: Private company. Main funding source(s): Abbott

Improvement Effect of PERMA Model-Based Nursing Intervention plus Music Therapy on Patients with Acute Liver Failure Undergoing Plasma Exchange Therapy.

Objective To explore the improvement effect of PERMA model-based nursing intervention plus music therapy (MT) on patients with acute liver failure (AHF) undergoing plasma exchange therapy (PET). Methods This research included 100 AHF patients treated with PET in our hospital, between January 2020 and December 2021, including 54 cases receiving PERMA model-based nursing intervention plus MT (observation group, OG) and 46 cases receiving routine nursing (control group, CG). Clinical efficacy and liver function (LF) were compared between the groups. Prenursing and postnursing psychology, treatment compliance, sleep, pain, and quality of life were assessed, and patient satisfaction was investigated at discharge. Results The postnursing overall efficacy showed no evident difference between the groups (P > 0.05). The clinical efficacy was mainly markedly significant (50.00%) in OG and effective (43.48%) in CG. The overall response rate was not statistically different between groups (χ2 = 1.392, P > 0.05). OG presented better LF, treatment compliance, and sleep quality after nursing, with milder negative emotions and pain than CG (P < 0.05). A higher patient satisfaction rate was also determined in OG at discharge (P < 0.05). Conclusions PERMA model-based nursing intervention plus MT can effectively improve the psychological state, treatment compliance, and quality of life of AHF patients with PET and reduce pain sensation, which has promising clinical application value in the future.

Decreased Peak Left Atrial Longitudinal Strain Is Associated with Persistent Pulmonary Hypertension Associated with Left Heart Disease.

Pulmonary hypertension (PH) associated with left heart disease (PH-LHD) is the most common form of PH and has significantly higher morbidity and mortality. We estimated the prevalence of PH-LHD on the follow-up echocardiography and the role of left atrial (LA) function in PH-LHD. From the STRATS-AHF registry composed of 4312 acute heart failure (HF) patients, we analyzed peak atrial longitudinal strain (PALS) in 1729 patients with follow-up echocardiographic examinations during mean 18.1 ± 13.5 months. PH was determined by the maximal velocity of tricuspid regurgitation (TR Vmax ≥ 3.4 m/s). Persistent PH was found in 373 patients (21.6%). The PH-LHD group was significantly older, and the prevalence of atrial fibrillation (AF), hypertension, diabetes, and heart failure with preserved ejection fraction were higher compared with the no PH-LHD group. Baseline left ventricular end-systolic volume and PALS were lower, and LA diameter, mitral E/E’ ratio, and TR Vmax were higher in the PH-LHD group. In the multivariate analysis, PALS (HR = 1.024, p = 0.040) was a significant variable after adjustment of LA diameter and mitral E/E’. A decreased PALS of <12.5% was the best cutoff value in the prediction of persistent PH-LHD (AUC = 0.594, sensitivity = 65.3%, specificity = 46.1%). PH-LHD was associated with increased HF hospitalization (HR = 2.344, p < 0.001) and mortality (HR = 2.015, p < 0.001) after adjusting for age and sex. In conclusion, persistent PH-LHD was found in 21.6% in the follow-up echocardiography and was associated with decreased PALS (<12.5%). PH-LHD persistence was associated with poor clinical outcomes. Thus, AHF patients with decreased PALS, especially <12.5%, should be followed with caution.

Pulmonary Artery Pressures During Cardiopulmonary Exercise Testing Using Cardiomems

<h3>Purpose</h3> Continuous pulmonary artery (PA) pressure monitoring has proven its value in reducing heart failure and all-cause hospitalizations. Invasive hemodynamic testing has shown that exercise in HFrEF leads to a steep increase in PA pressures and this steep rise is independently associated with reduced peak Vo₂. PA pressure response during exercise is likely more closely related to outcomes than resting hemodynamics in HF. The significance and potentially prognostic value of measuring PA pressures during CPET testing in AHF patients is currently unknown. In this feasibility-study we describe PA pressure curves during CPET in a cohort of advanced HF patients. <h3>Methods</h3> 7 advanced HF patients (Etiology: 4 NICM, 3 ICM; age 61 ± 12y; EF 28 ± 15%; 86% on beta blocker) with CardioMEMS device underwent standard stationary bike - CPET. PA pressures were measured at rest, every 2 minutes during exercise and during recovery. <h3>Results</h3> Max VO2 was 13.3±5.2 ml/kg/min; average duration of exercise was 8:56 min. Mean resting PA pressure was 12.5±5.2 mmHg. Mean peak PA pressure was 26.7±10 mmHg. Mean PA pressures increased on average by 2.5-fold (± 1.14) (Figure 1). The slope of mPAP rise was 3.33±2.1. mPAP uniformly returned to baseline values within 3 minutes of recovery. Pt. 3 was admitted 1 week after CPET testing with subacute worsening HF symptoms and underwent OHT, all other patients continue to follow at the centralized HF program at our institution. <h3>Conclusion</h3> PAP assessment using CardioMEMS is feasible during CPET. mPAP rose sharply during exercise. In HF patients with invasive PA pressure monitor devices, exercise PAP assessment may be a valuable tool to assess for functional capacity with possibly prognostic significance.

Molecular mechanism and therapeutic potential of YiQi FuMai injection in acute heart failure

Abstract Funding Acknowledgements Type of funding sources: Foundation. Main funding source(s): The National Science Foundation for Distinguished Young Scholars of China Background Acute heart failure (AHF) is a significant public health problem related to the high mortality and rehospitalization rate of patients. Although drug development is never interrupted, no single drug has been proven to play a decisive role in improving the survival of AHF patients. In China, multi-component traditional Chinese medicine has been widely used to treat AHF. As a Chinese herbal injection included in medical insurance, Yiqi Fumai Injection can reduce the level of NT-proBNP in AHF patients, improve heart function, and alleviate symptoms and signs related to heart failure. To further evaluate the therapeutic effect of Yiqi Fumai Injection on AHF, a multi-center, double-blind, randomized controlled trial that intends to recruit 1270 patients is being carried out in China. However, the mechanism of Yiqi Fumai Injection in the treatment of AHF has not been clarified. To further explore the underlying mechanism, we used systematic pharmacology methods to explore the potential molecular mechanisms of biologically active compounds. Methods We used the databases of HERB, the Encyclopedia of Traditional Chinese Medicine (ETCM), the Comparative Toxicogenomics Database (CTD), Online Mendelian Inheritance in Man (OMIM), and GeneCards to predict the active ingredients and potential targets of Yiqi Fumai Injection in the treatment of AHF. STRING was used for PPI network construction and analysis. Cytoscape was used to build a network between Chinese medicine, ingredients and targets. The DAVID, GO, and KEGG databases were used to predict the potential pathways of Yiqi Fumai Injection for the treatment of AHF. Results We obtained 31 active compounds of Yiqi Fumai Injection from HERB and ECTM databases. By overlapping targets between YQFMI and AHF, a total of 240 potential targets for Yiqi Fumai Injection to treat AHF were selected. According to the H-C-T network topology analysis, the core compounds include beta-sitosterol, Uridine, Guanosine, and Stigmasterol. Sixteen protein targets had significantly higher node degrees than the average in the PPI network, including AKT1, JUN, TNF, EDN1, CASP3, ESR1, DLG4, PTGS2, NOS3, IL1B, C3, AR, LEP, CNR1, CHRM2, and DRD2. The PPI results showed that the potential therapeutic targets of YQFMI were densely enriched in pathways related to endothelial function, neuromodulation, and lipid metabolism.The same results were shown in GO and KEGG pathway enrichment. Conclusion Our results indicate that Yiqi Fumai Injection may achieve the goal of improving AHF-related symptoms by regulating the function of vascular endothelium and nerves and the biosynthetic pathway of lipid metabolism. These findings support previous studies and provide a reference for studying the mechanism of Yiqi Fumai Injection in the treatment of AHF. Abstract Figure.

In-hospital outcomes of acute heart failure according to left ventricular ejection fraction: a single-center retrospective cohort study

Abstract Funding Acknowledgements Type of funding sources: None. Background Acute heart failure (AHF) is a common cause of hospitalization and associated with high mortality rate. However, the study on outcomes of AHF patients classified by left ventricular ejection fraction (LVEF) in Thailand remains limited. Purpose To compared outcomes of AHF patients across LVEF categories. Methods We retrospectively analyzed all consecutive AHF patients who admitted during Jan 2018 to Dec 2019 and had been evaluated for LVEF during hospitalization or within the last 12 months prior to admission. Baseline characteristics, management and outcomes were compared between AHF with reduced LVEF (HFrEF; LVEF &amp;lt; 40%), mid-ranged LVEF (HFmrEF; LVEF 40–49%), and preserved LVEF (HFpEF; LVEF≥50%). Primary outcome was in-hospital mortality. Secondary outcomes were length of stay (LOS), 1-year all-cause mortality and 1-year heart failure (HF) readmission rate. Statistical differences with a p-value &amp;lt;0.05 were considered to be significant. Results A total of 614 patients were enrolled in the study (mean age 68.6 years, 52% male, 81% history of heart failure). Of those, there were 43%, 12%, and 45% of HFpEF, HFmrEF and HFrEF, respectively. The in-hospital mortality of HFpEF and HFmrEF were not significantly different from HFrEF (6.1% vs 4% vs 10.1%, respectively, p = 0.10). Similarly, there were no differences in LOS (the median LOS was 7 days, IQR 4-12, p= 0.34), 1-year all-cause mortality and 1-year heart failure (HF) readmission rate among these group (p &amp;gt; 0.05). Conclusion The outcomes of HFpEF and HFmrEF were as poor as that of HFrEF. These findings highlight the need for effective therapeutic strategies to improve prognosis of HFpEF and HFmrEF patients. Abstract Figure.