Brain Natriuretic Peptide Research Articles

Accuracy of brain natriuretic peptide and N-terminal brain natriuretic peptide for detecting paediatric pulmonary hypertension: a systematic review and meta-analysis.

Pulmonary hypertension (PH) is a life-threatening disease, especially in paediatric population. Symptoms of paediatric PH are non-specific. Accurate detection of paediatric PH is helpful for early treatment and mortality reduction. Therefore, we assessed the overall performance of brain natriuretic peptide (BNP) and N-terminal brain natriuretic peptide (NT-proBNP) for diagnosing PH in paediatric population. PubMed, Web of Science, Cochrane Library and Embase databases were screened since their respective inceptions until August 2023. A bivariate random model and a hierarchical summary receiver operating characteristic model were used together to evaluate and summarize the overall performance of BNP and NT-proBNP for diagnosing paediatric PH. Eighteen studies using BNP/NT-proBNP were assessed, comprising 1127 samples. The pooled sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR) and area under the curve (AUROC) of BNP/NT-proBNP were separately as 0.81, 0.87, 6.33, 0.21, 29.50 and 0.91, suggesting a good diagnostic performance of BNP/NT-proBNP for detecting PH in paediatric population. For BNP, the pooled sensitivity, specificity, PLR, NLR, DOR and AUROC were 0.83, 0.89, 7.76, 0.19, 40.90 and 0.93, indicating the diagnostic accuracy of BNP for paediatric PH patients was good. For NT-proBNP, the pooled sensitivity, specificity, PLR, NLR, DOR and AUROC were 0.81, 0.86, 5.59, 0.22, 24.96 and 0.90, showing that NT-proBNP could provide a good value for detecting paediatric PH. Both BNP and NT-proBNP are good markers for differentiating paediatric PH patients from non-PH individuals.

Empagliflozin protects the heart from atrial fibrillation in rats through inhibiting the NF-κB/HIF-1α regulatory axis and atrial remodeling

Atrial fibrillation (AF) is the most common form of sustained cardiac arrhythmia. The current study aimed to investigate the potential of empagliflozin (EMPA) to protect against acetylcholine (ACh)/calcium chloride (CaCl2)-induced AF in rats and elucidate the possible underlying mechanism of action. Rats were randomly assigned to five groups, as follows: CTRL group: received 1 ml/kg isotonic saline; AF group: received 1 ml/kg induction mixture of ACh/CaCl2 (60 µg ACh and 10 mg CaCl2 per ml); EMPA group: received 30 mg/kg EMPA; AF + EMPA10 group: received the induction mixture concurrent with 10 mg/kg EMPA; AF + EMPA30 group: received the induction mixture concurrent with 30 mg/kg EMPA. Our results showed that EMPA administration inhibited the AF-related electrocardiographic abnormalities and decreased the serum brain natriuretic peptide levels. EMPA treatment maintained the cardiac redox balance, as indicated by reduced levels of the lipid peroxidation biomarker malonaldehyde while enhancing the antioxidant glutathione levels. Moreover, EMPA markedly repressed ACh/CaCl2-induced C-reactive protein, tumor necrosis factor, and interleukin-6 production. Interestingly, EMPA administration strongly suppressed cardiac transforming growth factor beta1, collagen type I, and alpha-smooth muscle actin expression levels in the AF rats. These results were consistent with our histopathological findings, which revealed the ameliorative effect of EMPA on AF-induced inflammatory and fibrotic lesions. Mechanistically, EMPA dose-dependently downregulated nuclear factor-kappa B (NF-κB) and hypoxia-inducible factor (HIF)-1α expressions. Besides, it attenuated the pro-apoptotic active caspase-3 while augmenting the anti-apoptotic B-cell lymphoma 2 expressions. Furthermore, EMPA dose-dependently suppressed cardiac phosphatidylinositol 3-kinase (PI3K)/Akt signaling. In conclusion, this study demonstrates that EMPA intervention, within AF induction, protects against ACh/CaCl2-induced AF in rats, exerting powerful antioxidant, anti-inflammatory, anti-fibrotic, and anti-apoptotic effects. These effects are mainly mediated through the targeting of the NF-κB/HIF-1α regulatory axis in a dose-dependent manner.

Cross talk on therapeutic strategies: natriuretic peptides and inhibiting neprilysin in hypertension management.

Hypertension, a prevalent cardiovascular condition globally, remains a significant public health concern due to its association with increased cardiovascular morbidity and mortality. Despite the availability of various antihypertensive therapies, achieving optimal blood pressure control in patients remains a challenge. Valsartan/sacubitril (ARNi), marketed as Entresto by Novartis, combines valsartan, an angiotensin receptor blocker, with sacubitril, an inhibitor of neprilysin. Neprilysin is responsible for breaking down natriuretic peptides and other vasoactive substances. Inhibiting neprilysin prevents the degradation of natriuretic peptides, enhancing their beneficial effects on blood pressure regulation. Natriuretic Peptides, including atrial natriuretic peptide (ANP) and brain natriuretic peptides (BNP), play pivotal roles in regulating blood pressure and cardiovascular homeostasis by promoting vasodilation, natriuresis, and antagonizing the renin-angiotensin-aldosterone system. Therefore, this combo drug lessens sensitivity to natriuretic peptides and tackles the processes in hypertension that activate the renin-angiotensin-aldosterone system. This review provides an overview of how natriuretic peptides (NPs) contribute to blood pressure regulation for the treatment of hypertension through inhibiting neprilysin. It highlights the ARNi's dual action that works synergistically by blocking the harmful effects of angiotensin II on blood vessels while simultaneously increasing the levels of beneficial natriuretic peptides. Schematic representation of the mechanism of action of ARNi. Abbreviation: -Renin angiotensin aldosterone system (RAAS), Natriuretic peptides (NP), Atrial Natriuretic peptide (ANP), Brain natriuretic peptide (BNP), C-type natriuretic peptide (CNP), Angiotensin II (Ang II), Angiotensin receptor neprilysin inhibitor (ARNI).

The outcomes of electronic personal health records in patients with heart failure or coronary artery disease.

There are limited data on the efficacy of smartphone-based personal health records (PHRs) in patients with cardiovascular disease. This study aimed to examine the processes, outcomes and challenges associated with the implementation of integrated PHRs in patients with heart failure (HF) or coronary artery disease (CAD). This prospective single-group study evaluated the effects of a PHR system with the capability to capture electronic health records and vital signs in patients with HF or CAD. The outcomes measured were the 6-month changes in blood pressure (BP), body weight (BW), brain natriuretic peptide (BNP) levels, lipid profiles and haemoglobin (Hb) A1c levels. Between June 2021 and March 2022, we enrolled 111 patients (median age: 61years and 47% women) with CAD and/or HF. Over 6months, the PHR review count distribution was skewed: median 749 times (lowest 2, highest 5724)/180days, suggesting both low and excessive PHR users. After 3days, 23% of the patients discontinued inputting their vital signs and medication status. At 6months, compared with patients who discontinued, those who continued to input their vital signs (N=86) showed a significant decrease in their systolic BP and LDL-C levels but not in the diastolic BP, BW, BNP, HDL-C, triglyceride or HbA1c levels. The implementation of smartphone-based PHRs in daily practice is challenging for patients with HF or CAD. However, we observed positive indications of the benefits of PHR in these patients. UMIN000044369.

The prognostic value of cartilage intermediate layer protein 1 (CILP1) in patients with diabetic cardiomyopathy.

To measure the plasma levels of human cartilage intermediate layer protein 1 (CILP1) in patients with diabetic cardiomyopathy (DCM), and to investigate its association with the occurrence of major adverse cardiovascular events (MACE) in DCM. A total of 336 diabetic patients were enrolled and assigned into two groups based on the presence or absence of DCM (DCM group and N-DCM group). The baseline clinical data including glutamic-pyruvic transaminase (ALT), glutamic oxaloacetic acid transferase (AST), albumin, serum creatinine, glycosylated hemoglobin (HbA1c), C-reactive protein (CRP), and N-terminal pro brain natriuretic peptide (NT-proBNP) were recorded. Subsequently, plasma levels of CILP1 at admission were detected by the enzyme linked immunosorbent assay (ELISA) method. Echocardiographic parameters were also acquired for all patients. The association of CILP1 with LVEF, LVDD and CRP was determined. In addition, the occurrence of MACE was examined during the 12-month follow-up in the DCM group. The concentration of CILP1 in the DCM group was higher than in the N-DCM group [1329.97 (1157.14, 1494.36) ng/L vs. 789.00 (665.75, 937.06) ng/L, P < 0.05], higher in the MACE group than in the non-MACE group [1777.23 (1532.83, 2341.26)ng/L vs. 885.00 (722.40, 1224.91) ng/L, P < 0.05). Correlation analysis revealed that CILP1 expression was associated with LVEF, CRP and LVDD (r = -0.58, 0.29 and 0.44, respectively, P < 0.05). Analysis of a nomogram demonstrated that CILP1, sex, age, BMI, LVEF and LVDD could predict the occurrence of MACE in DCM patients at 12months (P < 0.05). The plasma levels of CILP1 were independently associated with a stronger discriminating power for DCM. Furthermore, inclusion of CILP1 as a covariate in the model caused a significant improvement in risk estimation compared with traditional risk factors for DCM [BASIC: AUC: 0.556, 95%CI: 0.501-0.610; BASIC + CILP1: AUC: 0.913, 95%CI: 0.877-0.941, P < 0.05] and MACE [BASIC: AUC: 0.710, 95%CI: 0.616-0.792; BASIC + CILP1: AUC: 0.871, 95%CI: 0.794-0.928, P < 0.05]. The serum concentration of CILP1 was increased in DCM patients. Elevated fasting plasma CILP1 levels was a robust diagnostic marker of DCM and was independently associated with an increased risk of MACE.

A Proteomics-Based Approach for Prediction of Different Cardiovascular Diseases and Dementia.

Many studies have explored whether individual plasma protein biomarkers improve cardiovascular disease risk prediction. We sought to investigate the use of a plasma proteomics-based approach in predicting different cardiovascular outcomes. Among 51 859 UK Biobank participants (mean age, 56.7 years; 45.5% male) without cardiovascular disease and with proteomics measurements, we examined the primary composite outcome of fatal and nonfatal coronary heart disease, stroke, or heart failure (major adverse cardiovascular events), as well as additional secondary cardiovascular outcomes. An exposome-wide association study was conducted using relative protein concentrations, adjusted for a range of classic, demographic, and lifestyle risk factors. A prediction model using only age, sex, and protein markers (protein model) was developed using a least absolute shrinkage and selection operator-regularized approach (derivation: 80% of cohort) and validated using split-sample testing (20% of cohort). Their performance was assessed by comparing calibration, net reclassification index, and c statistic with the PREVENT (Predicting Risk of CVD Events) risk score. Over a median 13.6 years of follow-up, 4857 participants experienced first major adverse cardiovascular events. After adjustment, the proteins most strongly associated with major adverse cardiovascular events included NT-proBNP (N-terminal pro B-type natriuretic peptide; hazard ratio [HR], 1.68 per SD increase), proADM (pro-adrenomedullin; HR, 1.60), GDF-15 (growth differentiation factor-15; HR, 1.47), WFDC2 (WAP four-disulfide core domain protein 2; HR, 1.46), and IGFBP4 (insulin-like growth factor-binding protein 4; HR, 1.41). In total, 222 separate proteins were predictors of all outcomes of interest in the protein model, and 86 were selected for the primary outcome specifically. In the validation cohort, compared with the PREVENT risk factor model, the protein model improved calibration, net reclassification (net reclassification index +0.09), and c statistic for major adverse cardiovascular events (+0.051). The protein model also improved the prediction of other outcomes, including ASCVD (c statistic +0.035), myocardial infarction (+0.023), stroke (+0.024), aortic stenosis (+0.015), heart failure (+0.060), abdominal aortic aneurysm (+0.024), and dementia (+0.068). Measurement of targeted protein biomarkers produced superior prediction of aggregated and disaggregated cardiovascular events. This study represents an important proof of concept for the application of targeted proteomics in predicting a range of cardiovascular outcomes.

Exercise limitations in amyloid cardiomyopathy assessed by cardiopulmonary exercise testing-A multicentre study.

Amyloid cardiomyopathy is caused by the deposition of light chain (AL) or transthyretin amyloid (ATTR) fibrils, that leads to a restrictive cardiomyopathy, often resulting in heart failure (HF) with preserved or reduced ejection fraction. This study aimed to determine whether cardiac output reduction or ventilation inefficiency plays a predominant role in limiting exercise in patients with amyloid cardiomyopathy. We conducted a multicentre prospective study in patients with AL or ATTR cardiomyopathy who underwent cardiopulmonary exercise testing across four centres. Patients were compared with a propensity-score matched HF cohort based on age, gender, left ventricular ejection fraction (LVEF), and peak oxygen consumption (VO2). Data from 267 amyloid patients aged 77 (72, 81) years, 86% male, with a median N-terminal pro B-type natriuretic peptide (NT-proBNP) of 2187 (1140, 4383) ng/L, exercise parameters of peak VO2 of 14.1 (11.6;16.9) mL/min/kg, a minute ventilation to carbon dioxide production (VE/VCO2) slope of 37.4 (32.5, 42.6) and a LVEF of 50% (44%, 59%) were analysed. We identified 251 amyloid cardiomyopathy-HF matches. Amyloid patients had a signifnicantly higher VE/VCO2 slope [37.4, inter quartile range (IQR): 32.7, 43.1 vs. 32.1, IQR: 28.7, 37.0, P<0.0001], NT-proBNP (2249, IQR: 1187, 4420 vs. 718, IQR: 405, 2161ng/L, P<0.001), peak heart rate (121±28 vs. 115±27 beats/min, P=0.007) and peak ventilation (51, IQR: 42, 62 vs. 43, IQR: 33, 53L/min, P<0.0001) with earlier anaerobic threshold (VO2 at AT: 8.9, IQR: 6.8, 10.8 vs. 10.8, IQR: 8.9, 12.7mL/min/kg, P<0.0001) compared with HF. Between amyloid patients, AL patients (n=27) were younger (63, IQR: 58, 70 vs. 78, IQR: 72, 81years, P<0.0001), had lower VE/VCO2 slope (35.0, IQR: 30.0, 38.7 vs. 38.0, IQR: 32.8, 43.1, P=0.019), higher end-tidal carbon dioxide partial pressure both at AT (35.1±4.8 vs. 31.4±4.7mmHg, P<0.001) and peak exercise (32, IQR: 28, 35 vs. 30, IQR: 26, 33mmHg, P=0.039) as compared with ATTR (n=233). A higher VE/VCO2 slope and an earlier AT, determining functional capacity impairment, was assessed in patients with amyloid cardiomyopathy compared with the matched HF cohort. Additionally, patients with ATTR might display more severe exercise limitations as compared with AL.

Factors Influencing the Development and Severity of Cognitive Decline in Patients with Chronic Heart Failure

Background and Objectives: Considering the increasing prevalence of chronic heart failure (CHF) and cognitive decline (CD) observed in recent decades and the complex interrelation between these two pathologies often encountered in the same patient, in this study, we aimed to highlight the connection between CHF, defined as recommended by the European Society of Cardiology guidelines, and CD, evaluated by employing five neuropsychological scales. Materials and Methods: Our study was conducted on 190 patients with very high cardiovascular risk profiles admitted between 5 September 2021 and 15 November 2023 in the Municipal Emergency Hospital Timisoara. Of these, 103 had CHF (group A) and 87 did not (group B). Results: Although similar concerning age, sex distribution, and risk factors (excepting lipid profile), patients from group A had lower Mini Mental State Evaluation (MMSE) and Montreal Cognitive Assessment (MoCA levels (p = 0.003, respectively, p = 0.017) scores, more reduced daily activity (p = 0.021), and more severe depression (p = 0.015) compared to group B. We documented statistically significant correlations between left-ventricular ejection fraction (LVEF) and the levels of N-terminal pro–B-type natriuretic peptide (NT-pro-BNP), as well as with the results of MMSE (r = 0.226, p = 0.002 and r = −0.275, p = 0.005, respectively), daily activity, and depression (p ˂ 0.001). Multi-logistic regression models indicated age, blood pressure values, decreased daily activity, and depression as risk factors for CD in patients with CHF. Conclusions: In patients with CHF, there is an increased propensity of CD, with a direct relationship between MMSE and LVEF levels and an indirect one between MMSE and NT-pro-BNP levels. The concomitance of depression and reduced activity levels are aggravating CD in these patients.

Validation of Left Ventricular Filling Pressure Evaluation by Order of Tricuspid and Mitral Valve Opening in Patients With Atrial Fibrillation.

Accurate assessment of left ventricular filling pressure in patients with atrial fibrillation or flutter (AF) remains difficult. A novel 2-dimensional scoring system, visually assessing time difference between mitral valve and tricuspid valve opening (VMT) score, based on temporal analysis of early diastolic valve opening, could be applied to these patients. We aimed to determine the usefulness of the VMT score in patients with AF. We analyzed 119 consecutive patients with AF who underwent cardiac catheterization as a derivation cohort. The diagnostic performance of the VMT score was further evaluated in an external data set containing 189 patients with AF. Elevated left ventricular filling pressure was defined as a mean pulmonary arterial wedge pressure ≥15 mm Hg. The time sequence of atrioventricular valve opening was visually assessed and scored (0, tricuspid valve first; 1, simultaneous; 2, mitral valve first). When the inferior vena cava was dilated, 1 point was added, and the VMT score was finally graded as 0 to 3. Conventional Doppler parameters to estimate left ventricular filling pressure were also measured. Pulmonary arterial wedge pressure was elevated with an increase in the VMT score (0: 10±3, 1: 13±5, 2: 22±7, 3: 27±6 mm Hg; P<0.001), resulting in a significant rise in pulmonary arterial wedge pressure from VMT score 1 to 2. VMT≥2 predicted elevated pulmonary arterial wedge pressure with an accuracy of 87%, and the diagnostic accuracy of the VMT score was significantly higher than that of conventional Doppler parameters (C index, 0.88 versus 0.54-0.68; P<0.001). In addition, VMT ≥2 showed an incremental predictive value over plasma brain natriuretic peptide levels (C index, 0.79-0.93; P<0.001). In the external validation cohort, VMT≥2 demonstrated acceptable accuracy of 72%. VMT scoring was a useful echocardiographic marker of elevated left ventricular filling pressure and had an incremental benefit over practical biomarkers in patients with AF.

Abstract 4128526: Brain Natriuretic Peptide is Not Predictive of Days Alive and Out of Hospital During the Interstage Period in Infants with Hypoplastic Left Heart Syndrome

Background: Infants with hypoplastic left heart syndrome (HLHS) have the highest risk of morbidity and mortality during the interstage period. Brain natriuretic peptide (BNP) is frequently measured during the Stage I palliation (S1P) hospitalization. However, there is limited data on the association of BNP with interstage morbidity and mortality. In this context, we sought to examine the association between maximum BNP during the S1P hospitalization and last BNP prior to S1P discharge with days alive and out of hospital (DAOH) during the interstage period. We hypothesized that patients with higher BNPs during their S1P hospitalization would have fewer DAOH during the interstage period. Methods: We performed a single-center retrospective cohort study of infants with HLHS who underwent S1P at our institution between December 1, 2010 and December 31, 2022. Subjects were categorized based on maximum BNP and pre-discharge BNP tertiles. DAOH was calculated by subtracting the number of days hospitalized from the number of days alive during the interstage period. Multivariable zero-truncated negative binomial regression models were used to examine whether there was an association between BNP and DAOH. Models were adjusted for demographic, operative, and discharge characteristics and included an offset for interstage duration. Results: Of 251 infants, 221 (88%) had at least one BNP measured during their S1P hospitalization. The median maximum BNP was 529 (289-944) pg/mL, pre-discharge BNP was 346 (216-589) pg/mL, and DAOH was 97 (89-100) per 100 interstage days. The median maximum BNP in patients who remained admitted during the interstage period (n=32) was 1,027 (446-1,968) pg/mL which was significantly higher than the study cohort (p&lt;0.001). Patients in the maximum BNP upper tertile were more likely to have moderate to severe atrioventricular valve regurgitation (p=0.04) and had higher pre-discharge and pre-Stage 2 palliation BNPs (p&lt;0.001). There was no association between either maximum BNP or pre-discharge BNP with DAOH. Patients in the maximum BNP upper tertile had significantly more BNPs collected during their S1P hospitalization and interstage period. Conclusions: BNP during the S1P hospitalization is not predictive of interstage DAOH. In patients deemed candidates for discharge after S1P, repeated BNP measurements may have limited utility. Further work is needed to assess the association between BNP measured in the interstage period and longer-term outcomes.

Abstract 4137311: Inhibition of IL-33 by tozorakimab in patients with diabetic kidney disease: Cardiovascular insights from FRONTIER-1

Introduction: Interleukin-33 (IL-33) is a potent mediator of injury-induced local inflammation. Soluble ST2 (sST2), a decoy receptor of IL-33, is a prognostic serum biomarker for heart failure (HF). Here, we evaluated the impact of tozorakimab, an IL-33-neutralizing monoclonal antibody, on sST2-related secondary cardiac endpoints. Methods: FRONTIER-1 was a 24-week phase 2B study (NCT04170543) in patients with diabetic kidney disease (DKD). Key cardiac exclusion criteria were: 1) NYHA Class 3/4; 2) Left ventricular ejection fraction (LVEF) &lt; 40%; 3) B-type natriuretic peptide (BNP) &gt; 200 pg/mL. Local echocardiography (LVEF) was performed at Screening and Week 24. For exploratory analysis, echocardiography recordings were evaluated by a core laboratory. Throughout the study, BNP and sST2 were assessed and adverse events (AE) recorded. Safety and tolerability were evaluated for all dosed participants (Safety Analysis Population, SAP). Results: 573 participants were included in the SAP (139 = placebo / 434 = tozorakimab). Baseline characteristics were balanced across treatment groups. Tozorakimab was generally well tolerated and the incidences of AE, serious AE (SAEs), discontinuations, and death were similar to placebo. In the placebo group, cardiac disorder AE were reported in 6.5%, and SAE in 2.2%. Decline in LVEF of &gt; 10% was seen in 5 participants (4.3%). None developed BNP &gt; 200 pg/mL or clinical signs of HF. 1 participant (0.7%) presented with clinical symptoms of HF (SAE) without significant changes in LVEF or BNP. On tozorakimab, cardiac disorder AE/SAE were less frequent (3.7%/1.8%). Decline in LVEF of &gt; 10% was observed in 31 participants (8.3%), with 3 showing BNP elevation to 200–308 pg/mL. Two of these participants (0.5%) developed clinical signs of HF with LVEF 55%/30% and BNP &lt; 200 pg/mL. No further AE related to HF were reported for tozorakimab. Central analysis of LVEF revealed a substantial variability of site-based measurements indicating LVEF reductions &gt; 10 % in 2 (3.7%) participants on placebo and 6 (2.9%) on tozorakimab. Furthermore, central exploratory analysis demonstrated a slight increase in LVEF from baseline (1.62%, 95% CI: 0.22, 3.03) and a reduction in average E/e' (-0.47, 95% CI: -0.93, -0.01) for tozorakimab, but not placebo. Trends in BNP and sST2 over time were comparable. Conclusion: This study suggests a favorable cardiac safety profile for tozorakimab in patients with DKD. IL-33 inhibition did not elevate serum sST2 significantly.

Abstract 4125729: Elevated Pre-Procedural Serum Natriuretic Peptide Levels Are Associated with All-Cause Mortality in Patients Undergoing Transcatheter Edge-to-Edge Mitral Valve Repair: A Systematic Review and Meta-Analysis

Background: Transcatheter edge-to-edge mitral valve repair (TEER) is an established procedure in patients with severe mitral regurgitation (MR) and elevated surgical risk on optimal medical therapy. However, there remains considerable mortality in this patient population. Some studies have shown that serum brain natriuretic peptide (BNP) and N-terminal pro b-type natriuretic peptide (NT-proBNP) predict all-cause mortality after TEER, whereas other studies have shown mortality to be independent of these markers. To address this gap in knowledge, we sought to examine the existing literature to determine whether there is an association between pre-procedural serum natriuretic peptides and mortality after TEER. Hypothesis: Among patients undergoing TEER, elevated pre-procedural BNP and NT-proBNP are associated with increased all-cause mortality. Methods: Databases including MEDLINE, Embase, and Cochrane Library were searched from inception through September 2023 for studies assessing pre-procedural serum natriuretic peptide levels and mortality among patients undergoing TEER. Pooled hazard ratios (HR) and standardized mean differences (SMD) were calculated using a random-effects model estimated by restricted maximum likelihood with the Hartung-Knapp modification. Results: A total of 30 studies comprising 10259 patients undergoing TEER met inclusion criteria. 25 studies measured NT-proBNP and 5 studies measured BNP. Elevated pre-procedural NT-proBNP (&gt;5000 or &gt;10000 pg/mL) was associated with increased all-cause mortality in both adjusted (HR = 2.94; 95% CI = 1.75 - 4.95; I2 = 46.8%) and unadjusted (HR = 5.16; 95% CI = 1.85 - 14.40; I2 = 0.0%) analyses (Figures 1 and 2). Pre-procedural BNP and NT-proBNP were also significantly lower among survivors at 12 months compared to non-survivors (SMD = 0.82; 95% CI = 0.37 - 1.27; I2 = 78.3%) (Figure 3). This association was demonstrated in patients with primary or secondary MR. Conclusions: Pre-procedural BNP and NT-proBNP levels are significant predictors of all-cause mortality in patients undergoing TEER for primary or secondary MR. This supports the inclusion of BNP or NT-proBNP in pre-procedural assessments to help inform patient discussions and guide post-procedural follow-up and monitoring.

Abstract 4121812: Longitudinal Trajectory-Based Classification of Heart Failure with preserved Ejection Fraction: A Machine Learning Approach

Background: Heart failure (HF) with preserved ejection fraction (HFpEF) is a complex syndrome characterized by heterogeneous pathophysiology and dynamic changes in cardiac structure and function. Current research predominantly focuses on left ventricular ejection fraction (LVEF) or left ventricular structures with predefined categories. This study hypothesized that applying unsupervised methodologies to longitudinal echocardiography will reveal distinct trajectory patterns in cardiac structure and function related to clinical outcomes in HFpEF patients. Methods: This retrospective cohort study, conducted at UC Davis Medical Center (2014 to 2022), consisted of adult patients with HFpEF. The inclusion criteria included ICD HF codes, a left ventricular ejection fraction (LVEF) ≥50%, and a Brain natriuretic peptide (BNP) ≥100 pg/ml or N-terminal-pro BNP (NT-proBNP) ≥225 pg/ml. Longitudinal data were analyzed using unsupervised machine learning, including UMAP for dimensionality reduction and Gaussian Mixture Models for clustering. Primary and secondary outcomes included all-cause mortality and changes in BNP levels, respectively. Results: The study included 1,626 patients. The cohort had a median age of 69 years, was 57.5% female, and 51.8% white. Three distinct echocardiographic trajectory patterns emerged (p&lt;.05) among the HFpEF cohort. Trajectory #1 (n=568) exhibited a high-stable pattern with the highest mortality rates, Trajectory #2 (n=512) showed a high-decreasing pattern with high mortality rates, and Trajectory #3 (n=546) had a low-increasing pattern with the lowest mortality rates. Trajectories varied significantly in baseline characteristics and longitudinal echocardiographic changes, with Trajectory #3 having a lower baseline left ventricular mass index (p&lt;.001) and a higher mean arterial pressure ( p =.001) compared to the other trajectories. Kaplan-Meier survival analysis indicated significant differences in survival among the trajectories ( p =.004). Conclusion: The study utilized unsupervised analysis of longitudinal echocardiographic data to identify three distinct HFpEF trajectories, each associated with unique clinical features and outcomes. These findings underscore the heterogeneity of HFpEF and highlight the potential trajectory-based patient stratification to improve targeted intervention strategies. Future validation in larger, multicenter cohorts is warranted to enhance HFpEF management and patient prognosis.

Abstract 4135517: Echocardiographic Biomarkers Enhance Mortality Predictions in Cirrhosis Patients

Introduction: Cirrhosis, a late-stage liver disease, is associated with numerous systemic complications, making long-term mortality prediction challenging. Traditional models like Child-Pugh and MELD are primarily designed for short-term (3-month) mortality. This study evaluates the impact of incorporating echocardiographic (echo) variables in predicting long-term mortality in cirrhosis patients. Methods: A retrospective cohort study was conducted using data from 60 patients with clinically diagnosed cirrhosis from Hippokration Hospital, Greece, spanning 2018 to 2022. Patients were followed for up to 52 months. Exclusion criteria included pre-existing cardiovascular diseases and significant co-morbidities. Patients were categorized into survived to end of study (n=31) and died during study (n=29) groups. Outcomes were analyzed using multivariate logistic regression and Cox proportional hazards models, and include parameters for age, blood pressure, lab-based biomarkers (potassium, pro-brain natriuretic peptide, hemoglobin, platelet count, aspartate transaminase, gamma-glutamyl transferase, uric acid), and echo/ecg measurements (QT interval, left ventricular (LV) ejection fraction, LV global longitudinal strain (GLS), left atrial GLS, annulus velocities, and E/A ratio). Results: The multivariate logistic regression model (MELD+) that included echo variables showed a 10% improvement in area under the curve (AUC: 0.901) compared to the MELD model alone (AUC: 0.817). MELD+ improved risk classification accuracy by nearly 10% with a conservative threshold. The Cox proportional hazards model with MELD+ also demonstrated superior performance (AUC: 0.923; C-index: 0.875; Brier Score: 0.097) compared to the MELD model alone (AUC: 0.892; C-index: 0.831; Brier Score: 0.134). The MELD+ model showed less variation in hazard ratio confidence intervals, indicating more consistent risk estimation. Conclusion: Incorporating echocardiographic measurements enhances the accuracy of long-term mortality predictions in cirrhosis patients. These findings suggest that cardiac imaging should be considered in risk assessments for cirrhosis patients, particularly for predicting survival beyond three months.

Abstract 4138014: Incidence and Association of Amyloidosis Found at Carpal Tunnel Release to Development of Cardiac Involvement

Background: Carpal tunnel syndrome (CTS) associated with transthyretin cardiac amyloidosis (ATTR-CA) may manifest 5 to 10 years prior to cardiac diagnosis. Transthyretin amyloidosis (ATTR) identification in the tenosynovium isolated during carpal tunnel release (CTR) may facilitate earlier ATTR-CA diagnosis and treatment. Hypothesis: Amyloid discovered at CTR will be associated with, and/or serve as a precursor for, cardiac involvement. Aim: We aimed to determine the frequency and type of amyloid found at CTR as well as the incidence of cardiac involvement and/or treatment indication. Methods: A retrospective analysis was conducted on a convenience sample of adults undergoing CTR from 01/05/2021 to 03/24/2023. Biopsy specimens with confirmed amyloid via Congo red staining were analyzed using mass spectrometry (MS) for subtyping. Patients with amyloid in tenosynovial tissue were offered cardiac evaluation with history and physical, electrocardiogram, B-type natriuretic peptide, troponin-I HS, echocardiogram, and TcPYP nuclear scintigraphy. Patients with light-chain amyloidosis (AL) were referred to oncology, while patients with ATTR were offered genetic testing. Results: A total of 578 patients underwent CTR with tenosynovial sample excision. Amyloid involvement by Congo red staining was found in 43 patients (7.4%), with a definitive subtype confirmed by MS in 30 patients (5.2%). Samples were insufficient to define subtypes in 13 patients. Sole ATTR was found in 27 patients (4.7%), both AL and ATTR were found in 1 patient, and sole AL was found in 2 patients. Of the 28 ATTR patients (the patient with both ATTR and AL included), 24 pursued genetic testing, revealing all had wild-type ATTR. Of these 28 patients, 21 underwent cardiac evaluation, for which 2 had cardiac involvement on TcPYP and started tafamidis therapy. The patients with concomitant ATTR and AL or sole AL did not have evidence of cardiac involvement, however, chemotherapy was initiated as indicated. Unfortunately, 1 patient with AL on CTR did not pursue an evaluation. Conclusion: Incidental amyloid tissue found at CTR is common and associated with occult involvement warranting therapy in a minority of cases. Future cardiac involvement is unknown, and this cohort will be followed to determine future incidence. A startling number of patients were found to have occult systemic AL discovered at CTR. These incidental diagnoses may trigger lifesaving interventions, which may otherwise go undiagnosed.

Abstract 4138545: Mitral Valve Replacement is associated with favourable Functional and Clinical Outcome as compared with Restrictive Mitral Annuloplasty in Patients with Severe Ischemic Mitral Regurgitation. A prospective longitudinal analysis

Background: Restrictive mitral annuloplasty (RMA) and chordal-sparing mitral valve replacement (MVR) are common options for treatment of chronic severe ischemic mitral regurgitation. Research question: in patients with severe ischemic mitral regurgitation the most effective surgical approach remains controversial Aim: to test whether MVR provides superior clinical and functional outcomes compared with RMA. Methods: a prospective longitudinal analysis on 187 patients (age: 66 ± 9 year; EF:35 ± 8 %) undergoing MVR or RMA and CABG for severe ischemic mitral regurgitation. Six-minute walking test and echocardiography were performed at preoperative baseline, at 1 year and at a median FU of 5 year (interquartile range: 2.9). Brain natriuretic peptide levels were also obtained. Mitral regurgitation was defined through a comprehensive and integrative approach. Recurrent mitral regurgitation was defined as a vena contracta ≥ 3 mm at follow-up, in patients with no persistent regurgitation at discharge. The primary outcome was a 5-year composite of all-cause mortality and rehospitalization for heart failure. Survival analysis was performed with Kaplan-Meier method. Cox regression analysis was used to verify any independent predictor of composite end-point Results: Baseline preoperative data were similar between the two group. Mitral valve replacement was performed in 49% of patients (n=92) and RMA in 51 % (n=95). At 5 year patients referred to prostheses showed significant improvement in six-minute walking test as compared to RMA (MVR: 290 ± 70 meters vs MRA: 165± 56 meters) (p &gt; 0.01) ( Figure 1 ). The brain natriuretic peptide values did not differ between the two group at 1 year whereas were significantly lower in the MVR group at 5 years (MVR: 135 pg/ml; interquartile range:100 vs RMA: 486 pg/ml; interquartile range: 68 (p&lt;0.01) ( Figure 2 ). At 5 years freedom from all-cause death and rehospitalization for heart failure was higher in the MVR group as compared to RMA (84 ±8.9% vs 61 ±12%, p&lt;0.01) ( Figure 3 ). According to the Cox analysis recurrent mitral regurgitation was found to be a predictor of clinical outcome (HR:5.4, 95% CI:1.3-23.2, p= 0.023). Conclusions: In patients with severe ischemic mitral regurgitation referred for surgery, chordal- sparing MVR and CABG may improve functional capacity, clinical outcome and brain natriuretic peptide levels, compared with RMA and CABG. The impact of these findings remains to be defined by larger studies on longer term

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 4118949: Factors Influencing Left Ventricular Function Recovery Following Left Ventricular Assist Device Implantation in Pediatric Dilated Cardiomyopathy: Insights from Single-Cell RNA Sequencing Analysis

Background and Objective: Heart transplantation is a recognized treatment for pediatric severe heart failure, but long-term issues necessitate alternative treatments. Some dilated cardiomyopathy (DCM) cases show left ventricular function recovery after LVAD implantation. This occurrence could lead to new treatments, but mechanisms are unclear. This study explores preoperative molecular factors interacting with LVAD's effects using single-cell transcriptomics on clinical samples. Methods: Twenty-five pediatric DCM patients underwent Berlin Heart EXCOR (BHE) implantation at our institution since 2013. Those with left ventricular ejection fraction (LVEF) improving by &gt;20% were in the Recovery group (R), others in Non-Recovery (NR). Single-cell RNA-sequence was performed on myocardial tissue from six patients (three per group). Differential gene expression and pathway analysis were conducted for each cell type. Findings were validated by comparing them with histological evaluation or clinical examination in all 25 cases. Results: R: 10 patients; NR: 15. R's weight was 6.3 kg, NR's 9.9 kg (p=0.049); LVEF: R 23%, NR 16.5% (p=0.61). In pseudobulk analysis of cardiomyocytes, upregulated genes in R included NPPB, MYL7, PCDH9. KEGG analysis indicated activation of Tight Junction and ECM receptor pathways in R. In fibroblasts, major extracellular matrix proteins were higher in R, GSL gene expression in NR. Plasma Brain Natriuretic Peptide (BNP) at BHE implantation was significantly higher in R; 2913 [1836-3990 (95% CI)] vs 1278 [667-1888] pg/ml (Image1,2). No differences in tissue fibrosis rates were found between the groups. Conclusion: Alterations in gene expression patterns in some cell clusters, including cardiomyocytes, may contribute to left ventricular function recovery post-BHE implantation in pediatric DCM patients. Plasma BNP levels correlated with gene expression alterations, suggesting both a potentially protective effect on cardiomyocytes and a useful marker of LV functional recovery. Further validation of these candidate genes may elucidate intracellular molecular mechanisms.

Abstract 4127345: National Cohort Study on Hypertensive Disorders of Pregnancy Among Women with Congenital Heart Disease: Insights from Multiple Centers

Background: Hypertensive disorders of pregnancy (HDP) are among the primary reasons for maternal and perinatal deaths globally. Encompassing chronic hypertension, pregnancy induced hypertension (PIH), and preeclampsia, HDP are among the most frequent complications encountered during pregnancy. Considering the emerging congenital heart disease (CHD) population globally, research on HDP in pregnancies with CHD is urgently needed. Methods: Outcomes for 2220 pregnant women with CHD were evaluated retrospectively from 1993 to 2016 and prospectively from 2017 to 2019 from 7 tertiary hospitals. Maternal death, cardiac complications, obstetric and offspring complications of completed pregnancies and their demographics, cardiac characteristics, and comorbidities were collected. To identify the risk factors for HDP, univariate and multivariate analysis were performed through logistic regression. Results: Of 2220 completed pregnancies with CHD from 7 tertiary institutions, 77 women had PIH, and 76 women had preeclampsia. The main CHD diagnosis of patients with PIH was shunt lesion (including ASD, VSD, and PDA), left heart abnormality (including AS/AI, BAV, and COA), and single ventricle (SV). The main CHD diagnosis of patients with preeclampsia was shunt lesion (including ASD, VSD, and PDA), left heart abnormality (including AS/AI and MS/MI), and right heart abnormality (including TOF, PS/PAS/PI, DORV and DCRV). In parturients with PIH, the mortality and incidence of heart failure were 2.60% and 15.58%, respectively. In parturients with preeclampsia, the mortality and incidence of heart failure were 6.58% and 23.68%, respectively. Pregnancies with HDP had a significantly higher incidence of adverse maternal and offspring events than pregnancies without HDP. Independent risk factors for HDP included multiple gestation, use of medically assisted reproduction, having elevated brain natriuretic peptide (BNP) level, delayed first ANC visit, and absence of strict antenatal supervision. Conclusion: In summary, the presence of HDP in women with CHD significantly increased the risk of mortality and morbidity for both the mother and the child, particularly in cases involving preeclampsia.

Abstract 4138269: The Association Between Automatically Assessed Broad P-wave and Cardiovascular Events in Patients with Cardiovascular Risks

Background: A broad P wave in electrocardiography reflects atrial remodeling and is associated with cardiovascular events. Although there are several reports on the association between a broad P wave and cardiovascular events, the association between automatically assessed P-wave duration and cardiovascular events in cardiovascular high-risk patients has not been clarified. Hypothesis: We hypothesized that a greater automatically assessed P-wave duration would be associated with cardiovascular events in patients with cardiovascular risk factors. Methods: We included 4,654 patients with access to automated electrocardiography (ECG) analysis of those in the Cardiovascular Prognostic Coupling Study in Japan (a registry of subjects with one or more cardiovascular risk factors, excluding patients with atrial fibrillation). Twelve-lead ECG was conducted, and the P-wave duration in each lead was analyzed automatically using the 12-lead ECG Analysis system (Fukuda Denshi, Tokyo). We selected the maximum P wave duration (Pmax) among the 12 leads. The primary endpoint was a composite endpoint (cardiovascular death, nonfatal myocardial infarction/stroke), and the secondary endpoint was heart failure hospitalization. We assessed two P-wave cut-offs (Pmax ≥ 140, 150 msec) in relation to cardiovascular events. Results: There were 218 patients with Pmax ≥140 ms and 123 patients with Pmax ≥150 ms. N-Terminal pro brain natriuretic peptide (NT-proBNP) was significantly higher in patients with Pmax ≥140 ms than in those with Pmax &lt;140 ms (median 134.0 vs. 65.7 pg/mL, p&lt;0.001). NT-ProBNP was also higher in patients with Pmax ≥150 ms than in those with Pmax &lt;150 ms (median 192.0 vs. 66.9 pg/mL, p&lt;0.001). The mean follow-up period was 53 ± 17 months. The primary endpoint occurred in 180 cases and the secondary endpoint in 73 cases. A broad P-wave defined as Pmax ≥140 ms was independently associated with the primary endpoint (hazard ratio [HR] 1.68, 95% confidence interval [CI] 1.04–2.70, p=0.034) but not with the secondary endpoint (HR 1.96, 95% CI 0.99–3.90, p=0.055) after adjustment for covariates including NT-proBNP. A broad P-wave defined as Pmax ≥150 ms was independently associated with both the primary endpoint (HR 2.08, 95% CI 1.06–4.09, p=0.034) and the secondary endpoint (HR 3.22, 95% CI 1.38–7.52, p=0.007). Conclusions: Automatically assessed P-wave duration of Pmax ≥ 150 ms was a significant predictor of cardiovascular events and heart failure.