Decompensated Heart Failure Research Articles

Subclinical Congestion Evaluated by Point of Care Ultrasound (POCUS) at Discharge Predicts Readmission in Patients with Acute Heart Failure: Prognostic Cohort Study

Background: Heart failure (HF) is a complex entity that increases the risk of adverse outcomes. Point of care ultrasound (POCUS) allows easy lung and systemic venous congestion identification. Using ultrasound to detect sub-clinical congestion at discharge may help predict readmissions and mortality. Outcomes: The primary outcome was to address 30-day rehospitalization, and as a secondary outcome we investigated readmission and mortality in patients with residual congestion assessed with POCUS. Methods: A prospective prognostic cohort study was conducted at a tertiary-level institution in Colombia. Patients with acute decompensated heart failure (ADHF) at discharge were evaluated using POCUS through lung ultrasound (LUS), portal vein pulsatility (PVP), and a composite assessment of residual congestion. Inclusion criteria were ADHF, over 18 years old, with a “warm-wet” clinical profile. POCUS was performed using an ultraportable device using LUS and PVP. Statistical analysis used logistic regression models to estimate the association between ultrasound congestion and outcomes. Results: A total of 100 patients were included. The population was mostly female, with a median age of 78 years; 59% were hypertensive, and 39% had type 2 diabetes. Median NT-ProBNP was 3878 pg/ml. At discharge, 55% of patient had an inferior vena cava (IVC) over 2 cm, 54% had interstitial syndrome, and 41% had PVP >30%. Regarding 30-day readmission, we found an odds ratio (OR) 7.22 (95% CI 2.7-19.3) for interstitial syndrome; for PVP >30%, an OR 24.61 (95% CI 7.7-78.1) and an OR 13.19 (95% CI 2.7-62.6) for composite of residual congestion. Conclusion: Patients with ADHF and sub-clinical congestion, evidenced in LUS and PVP, were more likely to have readmission within 30 days of discharge. These findings should be confirmed with clinical trials to assess the effectiveness of a POCUS-guided treatment.

Novel Biomarkers as Potential Predictors of Decompensated Advanced Chronic Heart Failure—Single Center Study

Background/Objectives: Heart failure (HF) remains a major therapeutic and diagnostic challenge nowadays. Albeit, acute decompensated HF is associated with several clinical signs such as dyspnea or edema, it remains a challenge to use easy accessible and suitable tools, such as biomarkers, to distinguish between patients at risk for an acute decompensation of their heart failure and compensated, stable HF patients. Existing biomarkers, such as natriuretic peptides or troponin, are not specific and can be elevated due to several other disease conditions, such as myocardial infarction, atrial fibrillation, or valve diseases. Therefore, the aim of this study was to analyze the predictive potential of four novel cardiovascular biomarkers—the soluble urokinase-type plasminogen activator receptor (suPAR), heart-type fatty acid binding protein (H-FABP), vascular cell adhesion molecule 1 (VCAM-1), and growth/differentiation factor 15 (GDF-15) for the detection of cardiac decompensation in patients with HF. Methods: In this study, 146 patients were prospectively enrolled and the serum biomarker concentrations were analyzed using Enzyme Linked Immunosorbent Assay (ELISA). We correlated the biomarker concentrations with clinical and biochemical parameters of all patients and the predictive value for detection of cardiac decompensation was assessed. Results: A significant increase in the levels of suPAR (1.6-fold-change, p < 0.0001), H-FABP (2.2-fold-change, p = 0.0458), VCAM-1 (1.6-fold-change, p < 0.0001), and GDF-15 (1.7-fold-change, p = 0.0009) was detected in all patients with acute decompensated HF in comparison to patients with compensated HF. Univariate logistic regression analysis revealed a significant association of biomarker plasma concentration with the risk for a cardiac decompensation (suPAR: p < 0.0001; VCAM-1: p < 0.0001, H-FABP: p = 0.0458; GDF-15: p = 0.0009). Conclusions: In conclusion, the investigated novel cardiovascular biomarkers suPAR, GDF-15, VCAM-1, and H-FABP could be a valuable tool to facilitate therapeutic decisions in patients with heart failure and suspicion of a cardiac decompensation. Parameters such as renal function should be taken into account. Further studies on novel biomarkers are required to find reliable, sensitive, and specific tools that will enable the early detection of patients with acute decompensation.

Liver Dysfunction as a Rare Presentation of ICD Lead-Induced Tricuspid Regurgitation: A Case Report

Abstract Background Implanted cardiac devices with right ventricular leads can cause tricuspid regurgitation and subsequent heart failure. In these patients, congestive hepatopathy because of tricuspid regurgitation is well documented, however the presentation of liver dysfunction without overt heart failure is rare. Case Summary We report a case of a 56-year-old man with presumed hypertrophic cardiomyopathy, presenting with jaundice without signs of decompensated heart failure, eight years post implantation of dual chamber implantable cardiac defibrillator (ICD). A workup for abnormal liver function, including a liver biopsy, determined congestive hepatopathy as the cause. Cardiac imaging revealed severe tricuspid regurgitation caused by right ventricular ICD lead causing tricuspid valve malposition. Management included both tricuspid valve replacement and extraction of ICD and there was an excellent recovery. Discussion This is a rare case where severe tricuspid regurgitation and congestive hepatopathy secondary to an ICD lead presented with jaundice in the absence of signs of decompensated heart failure. In patients with an implanted cardiac device presenting with signs of liver dysfunction, congestive hepatopathy secondary to tricuspid regurgitation should be considered.

Abstract 4120140: Catastrophic Bioprosthetic Aortic Valve Thrombosis: An Unappreciated Complication of Veno-Arterial Extracorporeal Membrane Oxygenation Support in Cardiogenic Shock

Description of Case: A 56-year-old male with a history of cardiac sarcoidosis with biventricular systolic heart failure (HF) and a bioprosthetic aortic valve presented with acute decompensated HF. Progressive cardiogenic shock and hemodynamic instability ensued, requiring urgent bedside placement of an intra-aortic balloon pump (IABP) which provided only marginal hemodynamic support. After extensive multidisciplinary discussion, emergent cannulation for veno-arterial ECMO (VA-ECMO) was performed at the bedside as a bridge-to-decision for advanced HF therapies. The IABP was left in place for LV venting. Within 72 hours, extensive bilateral pulmonary opacities had developed. It was later realized that true LV ejection (as evidenced by aortic pulsatility on the arterial line) was not present and had been masked by pseudo-pulsatility provided by IABP inflations and deflations. Compared to an echocardiogram done 7 days prior to VA-ECMO cannulation, the bioprosthetic leaflets were no longer opening, thrombosis of the AV had occurred, and thrombus formation along the ECMO venous drainage cannula was noted. Failure to achieve LV venting culminated in complete thrombosis of the entire LV and LA and the patient ultimately expired. Discussion: Bioprosthetic valve thrombosis is a lesser-known complication of VA-ECMO support, with most reports involving bioprosthetic valves in the mitral position. Indeed, bioprosthetic valve thrombosis occurs at a higher rate than native valve thrombosis during VA-ECMO support. However, bioprosthetic AV thrombosis is an extremely rare complication of VA-ECMO support and arguably results in a more catastrophic scenario as most traditional approaches to LV unloading are contraindicated. The optimal LV unloading strategy for these patients (IABP, Impella, surgical apical unloading, etc) is unknown. Data from large retrospective analyses have demonstrated extremely poor outcomes when prosthetic valve thrombosis occurs, and it is thus critical to prevent this complication from developing. In contrast to IABP counter-pulsation, the benefit of upfront transvalvular LV venting with an Impella device safeguards the presence of a direct LV vent in the event of bioprosthetic AV thrombosis and eliminates the false reassurance of IABP pseudo-pulsatility. Further studies are needed to better elucidate the optimal LV unloading strategy in patients with bioprosthetic valves, particularly in the aortic position.

Abstract 4117834: Utility of Abdominal Aortic Calcification Assessment for the Prediction of Major Adverse Cardiovascular Events in Liver Transplant Patients

Background: Cardiovascular disease is a leading cause of postoperative morbidity and mortality following liver transplantation (LT). Presence of abdominal aortic calcification (AAC) has been linked to cardiovascular events in the general population. We investigated whether AAC on pre-transplant computed tomography (CT) predicts major adverse cardiovascular events (MACE) post-LT. Methods: Consecutive LT patients between 2010-2018 from the Victorian Liver Transplant Unit (Australia) were included. Extent of AAC was quantified in a blinded fashion, with high AAC defined as a calcium score of ≥500. MACE was defined as any recorded episodes of acute coronary syndrome (ACS), ventricular arrhythmia, decompensated heart failure, or stroke. The primary outcome was post-LT MACE at 30 days and the secondary outcome was all-cause mortality at maximal follow-up. Results: Of 461 patients undergoing LT, 350 had suitable CTs for analysis, of which 90 (25.7%) had also undergone CT coronary angiography. High AAC was identified in 98 patients (28.0%). This finding demonstrated a moderate correlation with high coronary artery calcium score (CACS) ≥400 (r=0.52, p<0.001). Fifty-eight MACE occurred in 42 patients (12.0%) within 30-days. High AAC was associated with increased risk of 30-day MACE (OR=2.68 (95%CI 1.39-5.17), p=0.004), and long-term mortality (HR=2.52 (95%CI 1.29-4.92), p=0.007) at a median follow-up of 4.0 years. In addition, high AAC predicted an increased risk of ACS (OR 3.80 (95%CI 1.18-12.27), p=0.025), heart failure (OR 3.07 (95%CI 1.21-7.80), p=0.020) and atrial fibrillation (OR 2.04 (95%CI 1.02-4.07), p=0.048), with a trend to increased prevalence of ventricular arrhythmia (OR 2.67 (95%CI 0.84-8.50), p=0.10). Following multivariate analysis, high AAC remained a strong independent predictor of MACE (OR=3.49, 95%CI 1.21-10.06, p=0.021). Addition of AAC to the revised cardiac risk index (RCRI) improved model fit for predicting MACE (net reclassification improvement of 52.7% (p<0.001)). Conclusions: This study demonstrates for the first time that high AAC on routine abdominal CT scans is associated with a 3-fold increased risk of 30-day MACE post-LT, and improves cardiovascular risk prediction compared to traditional risk scores. Quantification of AAC may offer a simple method of improving cardiovascular risk assessment and implementation of preventative strategies in liver transplant patients, using pre-existing scans without additional cost or patient risk.

Abstract 4123391: CardioMEMS and Mavacamten: A Synergistic Approach in Managing Hypertrophic Obstructive Cardiomyopathy with HFpEF Phenotype

Introduction: Mavacamten is a cardiac myosin inhibitor that has been approved for obstructive hypertrophic cardiomyopathy (oHCM). The CardioMEMS PA (pulmonary artery) sensor allows remote pulmonary artery diastolic (PAD) pressure monitoring to adjust diuresis in heart failure with preserved ejection fraction (HFpEF). We present the case of a patient with oHCM and HFpEF where data extrapolated from CardioMEMS provided valuable insight to the hemodynamic impact of cardiac myosin inhibitors. Case: A 66-year-old female with hypertension, obesity and oHCM presented with worsening dyspnea and was evaluated for septal myectomy. However, surgery was deferred because of decompensated HFpEF, as evidenced by significant leg edema on exam, and severely elevated left and right-side filling pressure, with restrictive physiology on right heart catheterization. A CardioMEMS PA sensor was implanted to guide decongestion, however, escalation of diuresis was limited due to severe left ventricular outflow tract (LVOT) obstruction. PAD remained elevated at 20-30 mmHg. Due to the refractory LVOT obstruction and despite the use of maximally tolerated beta blockers, Mavacamten was initiated and escalated according to protocol. LVOT obstruction resolved on follow up echocardiogram. Without any adjustment in her diuretic regimen, her PAD decreased to 15-20 mmHg. On follow-up visit, the patient reported improvement in dyspnea and reduction in lower extremity edema. Discussion: Managing oHCM is challenging, particularly when complicated by HFpEF. Mavacamten has shown promise in reducing LVOT gradients and improving symptoms in oHCM. However, managing fluid status in these patients can be difficult due to the risk of exacerbating LVOT obstruction while optimizing filling pressures. Our case provides direct evidence that treating LVOT obstruction with a cardiac myosin inhibitor leads to improvement in decompensated heart failure, as evidenced by the reduction in PAD. Conclusion: Addressing LVOT obstruction is key to decongesting and managing heart failure in oHCM patients. In our case, the use of CardioMEMS PA sensor system allowed a novel perspective of assessing hemodynamic impact of cardiac myosin inhibitors.

Abstract 4124182: Depression Symptomatology as Predictor of Incident Major Vascular Outcomes: Results from the Hispanic Community Health Study/Study of Latinos

Background: Cardiovascular disease (CVD) has consistently been associated with higher depression symptoms and disorders. Conversely, fewer studies have shown that depression predicts risk of incident CVD and mortality. Objective: To examine the association of depression symptoms with incident major adverse cardiovascular events (MACE) among Hispanics/Latinos living in US. Methods: MACE-free Hispanic Community Health Study/Study of Latinos participants who underwent baseline evaluation between 2008-2011 (n=15,180) were included. MACE was defined as the composite of incident stroke, myocardial infarction (MI), or decompensated heart failure (HF), adjudicated using standard criteria up to year 2019. Depression symptoms were assessed at baseline with a 10-item Center for Epidemiological Studies Depression Scale (CES-D 10, range 0-30 points, 5 points increments), with clinically significant depression defined as CES-D 10 ≥10 points. The incident rate ratio (IRR) of MACE across CES-D 10 scores was determined using Poisson regression models, adjusting for baseline sociodemographic characteristics and Framingham Risk Scores. Analyses were weighted for complex survey design and non-response. Results: The mean age (95% CI) was 40.4 (39.9-40.9) years, and the mean CES-D 10 score was 8.4, 95%CI (7.2-9.5) for those with MACE vs 6.9, 95%CI (6.7-7.0) for individuals without MACE (p<0.05). Clinically significant depression symptoms were present in 29% of the population. There were 321 total MACE outcomes that occurred between baseline and year 2019, with 120 MACE occurrences in individuals with CES-D 10 ≥10 points. In the fully adjusted model, increasing CES-D 10 was associated with higher incidence of MACE (for all: IRR 1.22, 95% CI (1.10-1.36); for those with CES-D 10 scores ≥10: IRR 1.62, 95% CI (1.21-2.17). Additionally, participants with CES-D 10 scores ≥10 were 1.4 times more likely to develop MACE compared to those with CES-D 10 scores <10 (HR 1.41, 95% CI=1.13-1.83, Figure). Among MACE sub-components, incident HF was twice as high in the population with CES-D 10 ≥10 points versus those with CES-D 10 <10 points (HR 2.36, 95% CI (1.58-3.51)). Conclusion: The findings of this cohort study indicate that depression symptomatology is associated with incident overall MACE and HF, and that clinically significant depression symptoms further increased risk for MACE and HF, making early treatment of depression a possible target for decreasing CVD incidence.

Abstract 4122120: Prospective Implementation of a Cardiovascular Implantable Electronic Device Algorithm-Based Management Pathway in Routine Heart Failure Care

Introduction: More than 1 million patients in the US are hospitalized annually with heart failure (HF), many of whom have cardiovascular implantable electronic devices (CIEDs). CIEDs monitor physiologic variables that could identify subacute HF decompensation and impending HF hospitalization (HFH). One such algorithm is Medtronic’s TriageHF TM , which integrates nine diagnostic inputs from remote monitoring data to stratify patients into categories of low-, medium-, or high-risk of HFH in the next 30 days. Goals/Aims: To implement and evaluate a program in which two Veterans Health Administration (VHA) cardiology clinics receive high-risk TriageHF TM scores for patients with CIEDs, followed by contacting and assessing patients and then taking appropriate clinical action. Methods: From 1/18/24 to 4/19/24, TriageHF TM risk scores were calculated from both HF-specific remote transmissions that were scheduled every 30 days and unscheduled remote transmissions. Clinicians then contacted patients with high-risk scores regarding possible symptoms and provided an empiric 3-day diuretic intervention (initiation or dose augmentation), adjusted guideline-directed medical therapy (GDMT), or performed another clinical action as appropriate. Results: Among 358 patients with 1140 transmissions, 72 (6%) patients had a high-risk transmission. Mean patient age was 72.8 years, 346 (97%) were male, and 221 (62%) had a pre-existing diagnosis of heart failure. Of the 72 patients with high-risk transmissions, 67 (93%) were successfully contacted; 34 (51%) had no HF symptoms, 24 (36%) had mild to moderate symptoms, 2 (3%) had severe symptoms, 4 (6%) had non-HF symptoms, and 3 (4%) could not report symptoms. Of the 67, 57 (85%) reported adherence to medications and 17 (25%) were identified as likely having a non-HF related high-risk score. Forty-six (69%) had a clinical action taken in response to the high-risk score, including 28 (42%) with a diuretic intervention, 12 (18%) with GDMT augmented, and 25 (37%) with other actions, such as being referred to HF clinic. Conclusions: In this implementation study, clinicians contacted and assessed nearly all patients at high-risk for HF decompensation based on CIED remote monitoring data. Approximately 70% of patients had an actionable high-risk score, with approximately half prescribed empiric diuretics or augmented GDMT. A randomized clinical trial is needed to determine whether this algorithm and subsequent intervention improves clinical outcomes.

Abstract 4140168: Association of left and right branch blocks with clinical outcomes in patients with heart failure with preserved ejection fraction (HFpEF)

Background: Although left (LBBB) and right (RBBB) bundle branch blocks play a critical role in cardiovascular pathogenesis, the associations of LBBB and RBBB with cardiovascular (CV) outcomes, especially in patients with HFpEF is understudied compared with normal QRS. Aim: We assessed clinical outcomes of LBBB and RBBB in patients with HFpEF who were admitted for acute decompensated heart failure compared with those without bundle branch blocks. Method: A cross-sectional study was conducted using the National Inpatient Sample (NIS) database from 2019. We only included adult hospitalizations with HFpEF admitted for acute decompensated heart failure in the study. Hospitalized records were categorized into three groups (LBBB, or RBBB, and those with normal QRS). Clinical outcomes included atrial fibrillation (AF), ventricular fibrillation (VF), complete heart block (CHB), sick sinus rhythm (SSR), cardiac arrest (CA), length of stay (LOS) and in-hospital mortality. Propensity score (PS) inverse probability of treatment weighting and matching were applied to determine the association between BBB types and CV outcomes and validated associations in sensitivity analyses. Results: A total of 334511 hospitalizations with HFpEF included LBBB (6818, 2%) and RBBB (7948, 2.4%) were analyzed. Compared to normal QRS, LBBB was associated with VF (odds ratio [OR]=2.47, p<0.001), SSR (OR=1.72, p<0.001), CHB (OR=2.77, p<0.001) and longer LOS (relative risk [RR]=1.15, p<0.001) after adjusting for covariates in PS analysis. Similarly, RBBB was associated with AF (OR=1.30, p<0.001), VF (OR=1.59, p=0.033), SSR (OR=1.72, p<0.001), CHB (OR=2.81, p<0.001), CA (OR=1.19, p<0.001), and longer LOS (RR=1.08, p<0.001) [Table 1]. These associations remained consistent in multiple validation analyses including after additionally adjusting for obesity, hypertension and diabetes. Conclusion: In hospitalized records with acute decompensated HFpEF, BBB was associated with increased risk of CV outcomes and longer hospital length of stay. The extent of association with multiple CV outcomes varied according to RBBB and LBBB.

Abstract 4138716: A novel Urocortin-2 analog COR-1167 corrects cardiac and renal dysfunction on top of Empagliflozin in a rat model of acute decompensated heart failure

Introduction: Urocortin-2 (UCN-2) is a peptide belonging to the corticotropin-releasing factor family that has cardiovascular, renal, metabolic and anti-inflammatory actions and improves cardiac function in human heart failure (HF) and cardiorenal dysfunction in chronic HF models. However, UCN-2 has a short half-life and intravenous delivery limits its therapeutic use. COR-1167 was discovered as a stable UCN-2 analog with qd pharmacological effects when injected subcutaneously. Hypothesis: Whether COR-1167 exerts chronic cardiorenal protection in Acute Decompensated HF (ADHF) is unknown, and in particular on background of SGLT2 inhibition, therefore both treatments were tested in a rat model of ADHF. Methods: Rats had coronary artery ligation to induce MI and a reduced ejection fraction phenotype. Three months later, rats were treated with vehicle or Empagliflozin (Empa) at 10 mg/kg/day PO. One month after starting Empa, two acute decompensation events were induced by administrating NaCl solution (1.8 g/kg, PO) on Day 0 and Day 14. Empa treated ADHF rats received vehicle or COR-1167 (3 µg/kg/day) by SC injections starting at 12 hours after the first decompensation and all treatments continued for 14 days. The groups were ADHF, ADHF + Empa and ADHF + Empa + COR-1167 (n=7-10/group). Left ventricular (LV) hemodynamics (cardiac catheters), cardiac output (echocardiography) and LV tissue perfusion (magnetic resonance imaging), cardiac mitochondrial coupling and ATP production (Seahorse) were measured 1 day after the second decompensation, while urine volume (uVol) and urine Na + excretion (uNa + ) collected from metabolic cages were analyzed 7 days after the first decompensation. Results: Compared to ADHF control rats, Empa treatment had no effect on systolic blood pressure (SBP), cardiac output (CO), LV end systolic pressure volume relationship (LVESPVR), LV end diastolic pressure volume relationship (LVEDPR), mitochondrial coupling and ATP production, but it increased myocardial perfusion, uVol and uNa + excretion. Compared to ADHF + Empa rats, COR-1167 treatment increased SBP, CO, LVESPVR, myocardial perfusion, mitochondrial coupling and ATP production, uVol, uNa + , while decreasing LVEDPVR. Conclusion: In the setting of ADHF, significant cardiorenal benefits and decongestion occurred when COR-1167 was administered on top of an SGLT2 inhibitor.

Abstract 4135434: Effect of early nutritional guidance for patients with acute myocardial infarction: A single center retrospective cohort study

Introduction/Background: Acute myocardial infarction (AMI) stands as a major global cause of mortality. Various intervention strategies, such as pre-hospital care, reperfusion therapies, pharmacological interventions, dietary modifications, and exercise therapies, have been researched to improve patient prognosis. Research Question: There remains a lack of evidence regarding the impact of early nutritionist-led dietary guidance on the prognosis of AMI patients. Aim: This study aimed to elucidate whether nutritional guidance by nutritionists who have national qualifications would improve the mortality and the primary composite endpoint (including acute decompensated heart failure, stroke, and acute coronary syndrome) of patients following an acute myocardial infarction. Methods/Approach: A retrospective cohort study enrolling 409 AMI patients who underwent emergency percutaneous coronary interventions between September 1, 2015, and October 31, 2023. Nutritionists guided 223 patients (54.5%) during hospitalization in this study. The nutritional guidance used in our study was also based on the definition of adequate caloric intake of 25–30 kcal per ideal body weight (kg). Under an appropriate total energy intake, a fat energy ratio of 20–25% and a carbohydrate energy ratio of 50–60% are recommended, with protein and lipid restrictions depending on the disease state. Results/Data: During a median follow-up of 39 months, 24 cases of all-cause mortality (5.9%) and 6 cases of cardiovascular mortality (1.5%) were recorded. Kaplan–Meier curves demonstrated significantly higher incidence rates of death and primary composite endpoints among patients without nutritional guidance during hospitalization. The multivariate Cox regression model revealed early nutritional guidance as a significant predictor for long-term mortality but not for primary composite endpoints. Furthermore, undernourished patients, defined as those with a geriatric nutritional risk index of 98 or less, showed a similar prognosis to those with good nutritional status after receiving nutritional guidance, indicating that nutritional guidance improves prognosis. Conclusion: Nutritionist-led dietary guidance for patients with AMI can potentially improve total mortality and is expected to be more effective in undernourished patients. Further research is warranted to explore the physiological impacts of improved diets resulting from such guidance and their effects on enhancing prognosis.

Abstract 4147609: Hypoalbuminemia as predictor of poor functional status in hospitalized patients with advanced heart failure

Introduction: Timely involvement of palliative care services for patients with advanced heart failure (HF) improves symptom burden, functional status, and resource utilization. The Karnofsky Performance Scale (KPS) is an objective tool used by palliative care specialists to assess physical ability and guide palliative interventions. Patients with lower KPS have poor outcomes, however evidence linking clinical parameters such as New York Heart Association (NYHA) class, ejection fraction (EF), and albumin with KPS remains limited. Goals: To identify clinical parameters associated with poor functional status in hospitalized patients with advanced HF Methods: Individuals with acute decompensated HF admitted between 2021-2023, ineligible for advanced cardiac therapies, and referred to palliative care were included. Data collected encompassed demographic variables, clinical parameters (NYHA classification, KPS, comorbidities, EF, Brain natriuretic peptide (BNP), albumin, creatinine), and palliative care interventions (family meetings, advanced care planning discussions). Bivariate and multivariate analyses, utilizing Kruskal-Wallis and chi-square tests along with adjusted regression models, were conducted using R to compare characteristics, with a low KPS (≤40) as the primary outcome. Results: A total of 97 individuals were included, with a mean age of 68 ± 17.7 years, 32 (33.0%) were female. Hypoalbuminemia was directly associated with KPS. Patients with albumin levels ≤3 g/dL were more likely to have KPS ≤40 (OR 2.6 [CI 1.03-6.7], p=0.04). NYHA class, EF, serum creatinine, and comorbid conditions (chronic kidney disease, stroke, chronic obstructive pulmonary disease, dementia) were not significantly associated with KPS. Those with lower KPS scores had higher utilization of palliative care services for family meetings, although did not differ significantly in advanced care planning status. Conclusions: In our analysis of hospitalized patients with advanced HF, hypoalbuminemia had the highest predictive value for low functional status. Low KPS score was associated with increased utilization of palliative care services and higher rates of inpatient mortality.

Abstract 4118882: Decompensated Heart Failure Secondary to a Non-Coronary Sinus of Valsalva to Right Atrium Fistula: A Case Report

Introduction: Sinus of Valsalva aneurysm (SVA) accounts for 3.5% of all congenital cardiac anomalies. Rupture occurs in 35% of cases and can lead to life-threatening fistulas, predominantly involving the right ventricle or right atrium. Description of Case: 62-year-old female with hypertension and hypothyroidism presented to the ER with progressively worsening dyspnea over the past week. She also reported worsening lower extremity edema, orthopnea, and paroxysmal nocturnal dyspnea. Chest X-ray showed large pleural effusions. Her ejection fraction was 66% ejection fraction with a fistula between the right sinus of Valsalva and the right atrium on transthoracic echocardiogram (TTE) which was also seen on transesophageal echocardiogram (TEE). Her heart failure was due to the fistula as she had no coronary artery disease on coronary angiogram. She had cardiothoracic surgery for fistula repair. Postoperatively, she developed complete heart block requiring a permanent pacemaker. She had no further complications and was discharged home in good condition. Discussion: SVA affects the right sinus (94%), with the non-coronary (5%) and left sinus (1%) being less commonly involved. Aneurysm rupture typically forms a fistula into the right ventricle (60%), right atrium (29%), left atrium (6%), or left ventricle (4%), and rarely into the pericardial cavity (1%). Symptoms vary by rupture size and location. TTE is the initial diagnostic tool but has limited sensitivity (50%) for detecting fistulas, whereas TEE has a 90% sensitivity. Cardiac MRI and CT can further refine diagnoses, and cardiac catheterization assesses coronary arteries preoperatively. Surgical closure with a patch is the primary treatment for ruptured SVA, significantly improving survival rates compared to non-surgical management.

Abstract 4135476: The Cardiomyocyte Hypertrophy Inhibitor RFN-409, Identified by High Throughput Screening Assay, Suppresses Pressure Overload-induced Systolic Dysfunction in Mice by Suppressing p38 Activity

Purpose: When the heart is exposed to stresses such as myocardial infarction or hypertension, it undergoes compensatory hypertrophy in response. However, continuation of the stress causes this compensatory mechanism to fail, and eventually systolic dysfunction or decompensated heart failure occur. As the hypertrophy of individual cardiomyocytes has been observed in this process, controlling cardiomyocyte hypertrophy is a potential target the prevention and treatment of heart failure. In this study, we constructed a high throughput screening (HTS) assay using cardiomyocyte hypertrophy as an index parameter. Compounds that inhibit cardiomyocyte hypertrophy were selected from our low molecular compound library. Methods and Results: In the primary screening, cultured rat primary cardiomyocytes were treated with each compound at a final concentration of 1 µM and then stimulated with 30 µM phenylephrine (PE) for 48 hours. These cells were subjected to fluorescent immunostaining with α-actinin, and cardiomyocyte area was measured using an ArrayScan™ system. The hypertrophy inhibition rate (%) of each compound was calculated as [(PE(+) - compound) / (PE(+) - PE(-))] × 100. The compounds with a hypertrophy inhibition rate greater than 50% and less than 150% were selected as hit compounds. In the secondary screening, these hit compounds were evaluated based on the dose-dependency of cardiomyocyte hypertrophy inhibition and the inhibition of the mRNA levels of the cardiac hypertrophy response genes ANF and BNP using real-time PCR. From the 269 low molecular-weight compounds in the original compound library, eight were selected through the primary and secondary screenings. Among them, we focused on Reference Number 409 (RFN-409). Western blotting indicated that RFN-409 inhibited PE-induced p38 activation. Next, we investigated the effect of RFN-409 on heart failure. Eight-week-old male C57 BL/6J mice were subjected to transverse aortic constriction (TAC) surgery and then randomly assigned to intraperitoneal treatment with RFN-409 (3, 10 mg/kg) or vehicle for eight weeks. RFN-409 at 10 mg/kg significantly prevented TAC-induced increase in left ventricular posterior wall thickness and decrease in left ventricular fractional shortening. Discussion: RFN-409 suppressed TAC-induced development of heart failure, at least partially by inhibiting p38 activity. These findings suggest that RFN-409 may be an effective agent for heart failure therapy.

Acute Decompensation of Chronic Cardiac Failure in Elderly and Senile Persons: Focus on Renal Dysfunction

The heart and kidneys, as well as their synergy, are necessary conditions for maintaining hemodynamic homeostasis in the human body. Since the beginning of the 19th century, it has been recognized that cardiovascular and renal diseases often coexist and have a mutually aggravating effect on each other. During the aging process, involutive changes in organs and body systems, especially the cardiovascular and urinary systems, lead to many physiological and functional changes that can increase the risk of developing acute complications, including acute decompensation of chronic heart failure (CHF). The prevalence of CHF is increasing among the population of older age groups all over the world, which is explained not only by involutive changes in the cardiovascular system of the body, but also by the high frequency of concomitant diseases, in particular chronic kidney disease. Age-related changes in the urinary system also play an important role in maintaining homeostasis of the body, however, during the aging process, along with a decrease in the number of nephrons, a decrease in the concentration function of the kidneys is observed, as well as a change in their structural integrity. These involutive changes in renal tissue may complicate the diagnosis and treatment of conditions associated with acute decompensation of CHF. Therefore, consideration of age-related changes in the cardiovascular and urinary systems and their contribution to the development of acute decompensation of CHF represents an important area for further research and practical applications aimed at improving medical care and quality of life in older people. The review article examines scientific literature data on cardiorenal relationships in acute decompensation of chronic heart failure in elderly and senile people.

Clinical and Demographic Characteristics of Patients Hospitalized for Decompensated Heart Failure with Extremely High NT-proBNP Levels

Background: NT-proBNP levels with a wide range at admission play both a diagnostic and a prognostic role in patients with HF. The differences regarding the clinical profiles and demography in decompensated HF patients according to NT-proBNP levels at admission are not clear. Methods: This study aimed to analyze and compare clinical profiles and demographics in patients hospitalized for decompensated heart failure according to levels of NT-proBNP at admission. The study included 302 patients hospitalized for decompensated HF who were divided into three groups based on admission NT-proBNP levels: group A (n = 46, with NT-proBNP level < 3000 pg/mL), group B (n = 130, NT-proBNP level between 3000–10,000 pg/mL), and group C (n = 126, NT-proBNP level > 10,000 pg/mL). Results: Patients hospitalized with decompensated HF and very high levels of NTproBNP, above 10,000 pg/mL at admission, are older, have a lower LVEF, higher NYHA class, more renal dysfunction, and longer hospital stay, resulting in a more severe clinical profile. Conclusions: The presence of very high levels of NT-proBNP may identify a category of patients with a more severe prognosis that requires more aggressive management and closer follow-up.

Predictors of acute kidney injury in chronic kidney disease patients treated for cardiovascular disease in the cardiac intensive care unit (MORCOR-TURK subgroup analysis).

Acute kidney injury (AKI) is a common complication in chronic kidney disease (CKD) patients in the cardiac intensive care unit (cardiac ICU). In this study, we aimed to identify predictors of AKI in CKD patients treated in the cardiac ICU for cardiovascular diseases. The MORCOR-TURK trial was conducted as a multicenter, prospective, cross-sectional, and noninterventional investigation. A total of 3157 patients treated in the cardiac ICU were enrolled from 50 centers over the course of one month. In this subgroup analysis, 615 patients with CKD treated in the cardiac ICU for cardiovascular disease were included in the study. The primary outcome of this study was the development of AKI. During hospitalization, patients who developed AKI were identified. AKI developed in 288 patients (46%). After multivariable analysis, decompensated heart failure (OR: 3.72, p = 0.005), primary percutaneous coronary intervention (OR: 3.75, p = 0.004), non-primary percutaneous coronary intervention(OR: 2.85, p = 0.033), troponin levels (OR: 1.04, p = 0.031), and need for mechanical ventilation (OR: 3.11, p < 0.001) were identified as independent predictors of AKI development in CKD patients. Our efforts to identify AKI predictors in cardiac ICU patients with CKD have yielded directly applicable results in clinical practice. AKI can be prevented by developing personalized strategies to follow up and treat cardiac ICU patients with CKD who have decompensated heart failure, are undergoing percutaneous coronary intervention (primary and non-primary), have high troponin levels, and need mechanical ventilation.

Subcutaneous furosemide in heart failure: a systematic review.

Intravenous loop diuretics are the primary treatment for congestion in patients with decompensated heart failure (HF). Furosemide is the most commonly used loop diuretic and is licensed for administration either orally, intramuscularly or intravenously but not subcutaneously. Recently developed, pH-neutral, concentrated, 'skin-friendly' preparations of furosemide have been developed which allow subcutaneous administration. In this systematic review, we summarize and critically appraise the current evidence for subcutaneous furosemide in patients with HF. The electronic databases MEDLINE, EMBASE, the Cochrane Library, and ClinicalTrials.gov registry were searched up to 31 December 2023. Of the 17 studies identified, 5 were randomised controlled trials (RCTs), 2 were non-randomised controlled studies, 3 were prospective observational cohort studies, and 7 were retrospective observational studies.All RCTs utilised novel pH-neutral, subcutaneous preparations of furosemide. Bioavailability of novel subcutaneous preparations were similar to intravenous furosemide 10mg/ml: 99.7% for an 8mg/ml preparation and 112% for a 30mg/ml preparation. Natriuresis and diuresis were also similar with novel subcutaneous and conventional intravenous furosemide. Adverse events of novel preparations included infusion site pain or discomfort, localised skin erythema and minimal swelling. All studies of conventional subcutaneous furosemide were non-randomised with very limited data re bioavailability or diuretic and natriuretic effect. Conventional subcutaneous furosemide was associated with substantial skin irritation (affecting 3-23% of patients), and skin infections requiring treatment with antibiotics (3-17%). Novel, pH-neutral preparations of subcutaneous furosemide achieved similar diuresis, natriuresis, and bioavailability to intravenous furosemide, and were well tolerated. Novel preparations may be a treatment option for patients with HF.

Minute Ventilation/Carbon Dioxide Production Slope Could Predict Short- and Long-Term Prognosis of Patients After Acute Decompensated Heart Failure

(1) Background: Heart failure (HF) leads to functional disability and major cardiovascular events (MACEs). Cardiopulmonary exercise testing (CPET) is the gold standard for assessing aerobic capacity and prognostic stratification. This study aimed to evaluate the predischarge CPET variables in patients with acute decompensated HF and identify the submaximal CPET variables with prognostic value. (2) Methods: A retrospective cohort study was conducted at a tertiary center in Taiwan. Patients surviving their first episode of decompensated HF and undergoing predischarge CPET (February 2017 to January 2023) were analyzed. Follow-up was conducted until a MACE or administrative censoring (up to 5 years). Cox regression identified the significant predictors of MACE. (3) Results: The study included 553, 485, and 267 patients at the 3-month, 1-year, and 5-year follow-ups, respectively. MACE rates were 15.0%, 34.2%, and 50.9%. The VE/VCO2 slope was a significant predictor of MACE at all intervals. A VE/VCO2 slope &gt;38.95 increased the risk of MACE by 2.49-fold at 3 months and 1.81-fold at 1 year (both p &lt; 0.001). A slope &gt; 37.35 increased the 5-year MACE risk by 1.75-fold (p = 0.002). (4) Conclusions: The VE/VCO2 slope is a significant submaximal CPET predictor of MACE in patients post-acute decompensated HF for both short- and long-term outcomes.

Neuroimmune cross-talk in heart failure.

Heart failure (HF) is characterized by autonomic nervous system (ANS) imbalance and low-grade chronic inflammation. The bidirectional relationship between the ANS and immune system (IS) is named "neuroimmune cross-talk" (NICT), and is based on common signaling molecules, receptors, and pathways. NICT may be altered in HF, and neuroinflammation seems to be a main driver of HF progression. In HF, heightened sympathetic nerve activity triggers inflammatory cascades that lead to cardiomyocyte death and myocardial interstitial fibrosis. Concurrently, parasympathetic withdrawal may impair the cholinergic anti-inflammatory pathway, with a less effective immune response to infections or inflammatory events. Additionally, microglial activation and inflammatory molecules contribute to autonomic imbalance by acting on central nuclei and peripheral visceral feedbacks, which in turn promote adverse cardiac remodeling, HF decompensation, and potentially life-threatening arrhythmias. Therefore, neuroinflammation has been identified as a potential target for treatment. Pharmacological antagonism of the neurohormonal system remains the cornerstone of chronic HF therapy. While some drugs used in HF management may have additional benefits due to their anti-inflammatory properties, clinical trials targeting inflammation in patients with HF have so far produced inconclusive results. Nevertheless, considering the pathophysiological relevance of NICT, its modulation seems an appealing strategy to optimize HF management. Current research is therefore investigating novel pharmacological targets for anti-inflammatory drugs, and the immunomodulatory properties of denervation approaches and bioelectronic medicine devices targeting NICT and neuroinflammation in HF. A deeper understanding of the complex relationship between the ANS and IS, as outlined in this review, could therefore facilitate the design of future studies aimed at improving outcomes by targeting NICT in patients with HF.