Reduction In NT-proBNP Research Articles

Real world evidence of Sacubitril/Valsartan in octogenarian patients with heart failure. Results From the PARACHUTE-HF Study

Abstract Introduction The beneficial effects of Angiotensin Receptor Neprilysin Inhibitors (ARNI) on heart failure (HF) patients, particularly those with reduced left ventricular ejection fraction (LVEF), have been highlighted in several randomized controlled trials. Since 2020, ARNI has been available for HF treatment in Japan, a country known for its aging population. However, the inclusion of octogenarians in previous trials has been limited, leaving a gap in evidence regarding ARNI's effectiveness in the elderly. Objective This study aims to explore the real-world efficacy and safety of ARNI treatment among octogenarian HF patients in Japan, reflecting its status as a leading aging society. Methods The Prospective Area Registry of ARNI for Congestive Heart failUre in Tokyo East (PARACHUTE) trial, a multicenter registry, was conducted. It involved patients newly prescribed ARNI for chronic HF regardless of LVEF between 2020 and 2021. We compared patient backgrounds, changes in NT-proBNP levels at 6 months, and the rate of ARNI discontinuation between groups aged below and above 80 years. Results The study enrolled 105 patients, with an average age of 75 years. Forty-six patients (44%) were over 80 years old, and the majority (72%) were male. Among the younger group, 50% had preserved LVEF, compared to 32% in the octogenarian group (p=0.01). Median NT-proBNP levels across all patients decreased significantly from 2,540 pg/mL at baseline to 998 pg/mL at 6 months. The reduction in NT-proBNP was similar between the two age groups, with no significant interaction (p=0.46). Discontinuation rates due to any cause were not significantly different between younger and older patients (7% vs. 13%, p=0.28). Conclusion ARNI treatment resulted in significant reductions in NT-proBNP levels in HF patients, both under and over 80 years of age, with comparable discontinuation rates. These findings highlight the effectiveness and safety of ARNI in the management of chronic HF in the elderly, offering valuable real-world evidence from Japan's unique demographic context.

Prognostic value of alveolar surfactant type-B in acute heart failure: a long-term comparative analysis vs NT-proBNP

Abstract Background In heart failure (HF) biomarkers are an integral component of prognostic assessment. Natriuretic peptides are the gold standard, but they do not directly reflect lung vascular injury. Surfactant type B (Surf-B) is released by type 2 alveolar cells under pressure induced trauma, with few reports just addressing its plasmatic levels in stable chronic HF (CHF). Information on acute HF (AHF) is lacking. Purpose To clarify the prognostic value of Surf-B changes vs NT-proBNP levels after decongestion therapy and to compare their prognostic ability at 1-year follow-up. Methods Patients with acute pulmonary edema (APE) underwent a combined evaluation of Surf-B and NT-proBNP serum levels with quantification of B-lines at hospital admission (time 0), discharge (time 1) and at 1 year (time 2). Results 54 patients (mean age 72.1 ± 11 years; mean LVEF 36% ± 13%; 65% men) were enrolled. At time 1, the average Surf-B, NT-proBNP and B-lines were significantly reduced compared to time 0 (p<0.0001). No correlation between Surf-B and NT-proBNP was observed either at time 0 (r=-0.21; p=0.12) or at time 1 (r=0.05; p=0.71). Despite the significant decrease in Surf-B levels from time 0 to time 1, 18.5% of patients behaved as non-responders exhibiting no changes in Surf-B; conversely, only 5.5% did not show significant reduction in NT-proBNP, despite significant decongestion. 38 patients were followed up to time 2: of these, 13 (34%) reached the composite endpoint of death or hospitalization for HF. Surf-B measured at time 1 was a strong predictor of adverse outcome. Patients with Surf-B above median at discharge displayed a worse survival-free from HF hospitalization compared to the remainders (Log rank p=0.012) (Figure). Also, patients with Surf-B above median at discharge had a more than 4-fold increased risk of the composite endpoint (HR 4.5, 95%CI 1.4-20.2, p=0.023). Conversely, NT-proBNP at discharge was not significantly associated with HF-free survival (Log rank p=0.26) (Figure) and was not a significant predictor of the composite outcome (HR 1.9, 95%CI 0.6-9.3, p=0.25). At ROC analysis, discharge Surf-B levels showed a higher area under the curve (AUC=0.763, p=0.011) than NT-proBNP values (AUC=0.69, p=0.063). Conclusions These data suggest that Surf-B, an organ specific biomarker of lung injury, is highly sensitive to the effectiveness of decongestion therapy, outperforming NT-proBNP. Given the high rate of patients who do not improve their Surf-B levels over time, the reparative processes of alveolar break damage may dissociate from mere decongestion and cardiac healing in AHF.Figure:1yr Kaplan-Meier survival curves

Integrating artificial intelligence into a real-world clinical pathway to facilitate clinician treatment optimisation in patients with HFrEF on suboptimal medical therapy

Abstract Background Despite evidence-based pharmacological recommendations, many patients with HFrEF remain undertreated. (1) These patients remain at risk of decompensation and might benefit treatment optimisation. Many patients may also have been diagnosed with HFrEF prior to the use of sacubitril/valsartan or SGLT2 inhibitors. Identification of patients with historical HF diagnosis is time-consuming. Artificial intelligence approaches using deep learning might allow rapid identification of such patients. Aim To develop an artificial intelligence deep-learning algorithm for rapid identification of HF from electronic health records (EHRs) and to determine the potential benefit of our AI-driven algorithm for the detection of undertreated HFrEF patients in the community. Methodology In this study data was collected from EHRs of 1,200 patients who underwent transthoracic echocardiography. The records were screened to identify HF diagnosis through an AI deep-learning algorithm using a Convolutional Neural Network (CNN). Medication status of patients identified as having HFrEF was assessed to determine whether they were on optimal guideline-directed medical therapy. Accuracy of the AI algorithm was assessed by a manual clinician review in a subset of 150 patients. Eligible patients not on optimal medical therapy where no further optimisation was planned (judged to be "stable" at last visit) were invited for a clinical evaluation including NT-proBNP and Kansas City Cardiomyopathy Questionnaire (KCCQ) and offered a treatment optimization that could include either uptitration or initiation of a new medication if symptomatic. NT-proBNP and KCCQ were repeated at 12 week, pre- and post-optimization results were compared to evaluate patient outcomes. Results The deep-learning algorithm accurately identified HFrEF patients (99%) and use of RAAS inhibitors (97%) and beta-blockers (92%). 73 patients attended for initial clinical assessment (mean age 70 years, 77% male) and demonstrated a moderate level of HF-symptom burden (median NT-proBNP was 679 pg/mL, interquartile range was from 220 to 1300) and mean KCCQ overall summary score was 70, indicating a moderate level of HF symptom burden. 27 patients agreed to treatment optimisation. After 12 weeks there was a significant 22% reduction in NT-proBNP (from 1991 pg/mL (SD+/- 1796) to 1630 pg/mL (SD +/- 1588),p=0.049) and improvements in KCCQ (total symptom score 79 (+/-22) to 85 (+/-20), p=0.005; clinical summary score 78 (+/-23) to 82 (+/-20); overall summary score from 75 (+/- 24) to 80 (+/-22), both p=0.04). 23 patients (85%) and 18 patients (67%) out of 27 had an improvement in NT-proBNP and KCCQ overall summary scores respectively. Conclusion In our study we demonstrated the feasibility and potential benefits incorporating AI into a clinical workflow, allowing optimising treatment of patients with HF, with improvements in biomarkers and quality of life that could translate to long-term patient benefits.Changes in NT-proBNP after treatmentChanges in KCCQ after treatment

REDUCE-HF: a stronger heart go a long way

Abstract Introduction/Purpose Heart failure (HF) is a serious cardiovascular condition with a significant global health concern. The risk of heart failure rehospitalisation is high globally and locally, the 30-day HF readmission was about 32% from a local study (1). The study aims to adopt an intensive treatment strategy similar to Strong-HF trial (2) and evaluate rapid up-titration of guideline directed medical therapy (GDMT) and close follow-up will improve patients' outcomes after acute heart failure (AHF). Objectives The Reduction of Decompensation and Unnecessary Cardiac failure Emergency admissions: ambulatory Heart Failure service model (REDUCE-HF) is a non-randomised prospective study evaluating clinical outcome of patients discharged from AHF. Exclusion criteria included primary valvular disorders, end-stage renal failure and metastatic cancer. After HF discharge, eligible patients were recruited into our REDUCE-HF program irrespective of LVEF. They were subsequently managed in our ambulatory HF centre within two weeks, where intensive up-titration of GDMT and close follow-up would be proceeded. The data of our service model will be compared with our 5-year historical cohort. Primary outcome comprised of all-cause mortality and heart failure hospitalisation. Secondary outcome will be comparison of clinical and functional status at baseline and 3-month on follow up. Results Between October 2022, and December 2023, 245 patients were successfully recruited into our REDUCE-HF service model. Historical cohort of 6867 patients with primary diagnosis of acute heart failure were served as control (usual care pathway), data extracted from 2018 to 2022. Their mean age was 67.8+/-12.2 and 72.2%were male. 60% of them were HFrEF (EF<=40%) and 28% were ischaemic cardiomyopathy. The mean follow up period was 3 months. At 90 days, REDUCE-HF cohort group has shown much lower all-cause mortality than usual care group (2.5% vs 9.3%, HR 0.26, 95% CI 0.18-0.41, p<0.001). There was a much lower incidence of heart failure hospitalisation in REDUCE-HF group as compared to control (8.6% vs 13.1%, HR 0.65; 95% CI 0.55 to 0.74, p<0.01). In secondary outcome, there was significant reduction of NT-ProBNP of 45.2% (from 4229 to 2319pg/m, p<0.001), tremendous increment of 6-minute walk test (from 211 to 250m, p<0.001) and remarkable improvement of KCCQ score from 55.1 to 86.7, p<0.001. The overall LVEF was significantly increased from 39% to 44%, p<0.05. The positive outcome were attributed to good adherence to GDMT: ACEi/ARB/ARNI 91%, Betablocker 90.3%, MRA 72.4% and SGLT2i 95.5%. Conclusion The REDUCE-HF ambulatory service model has been proven effective in reducing mortality, decompensation and preventing unnecessary heart failure hospitalisation in this prospective study. By intervening proactively, this model not only enhances the quality of life but also hold promise in alleviating the burden of in-patient services on heart failure.

Thrombin generation, fibrin clot permeation and lysis in patients with severe mitral regurgitation undergoing transcatheter edge-to-edge mitral valve repair: mitral fibrin study

Abstract Background/Introduction The management of heart failure (HF), particularly in the context of reduced ejection fraction, is further complicated by an increased risk of thromboembolic events. Structural alterations of both left ventricle and mitral valve contribute to mitral regurgitation (MR). However, the body of evidence provides inconclusive insights into the relationship between MR and thromboembolic risk. Purpose This study aimed to investigate the impact of transcatheter edge-to-edge repair (TEER) on thrombin generation, clot permeation and clot lysis time in HF patients with severe MR eligible for mitral TEER. Methods A cohort of 31 HF patients with severe MR undergoing TEER underwent systematic evaluation at three time points. Coagulation parameters, including fibrinogen concentration, thrombin generation, fibrin clot permeability (Ks), and clot lysis time (CLT), were assessed. Comprehensive evaluations also covered echocardiographic, laboratory, and clinical parameters. Results TEER induced changes in fibrinogen levels (p=0.009, visit 3 vs. visit 2) and improved fibrin clot properties over a 50-day follow-up (Ks, p=0.005, visit 3 vs. visit 2). No significant differences were observed among time points in analyzed blood clot parameters. Linear regression, incorporating thrombin generation variables, Ks, and CLT for delta NT-proBNP, highlighted CLT as the sole predictor of NT-proBNP change between visit 2 and visit 1 (p=0.03; R2=0.18). Conclusions MR reduction through TEER led to transient alterations in fibrinogen concentration and improved fibrin clot characteristics. Additionally, baseline CLT emerged as a significant predictor of early NT-proBNP reduction, emphasizing its role as a key indicator of the hemodynamic response to TEER.

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.

The effect of bachmann bundle pacing on diastolic function in patients with non-obstructive HCM

Abstract Background and Objective Patients with non-obstructive HCM (nHCM) have advanced diastolic dysfunction and atrial remodeling, leading to increased heart failure hospitalisations. The objective of this study was to evaluate the role of Bachmann bundle pacing (BBP) in diastolic filling compared to right atrial appendage pacing (RAAP). Methods Forty patients with symptomatic nHCM and normal LV function were prospectively enrolled from January 2021 to June 2023. Inclusion criteria included electrocardiographic evidence of inter-atrial delay, E/e’ &amp;gt; 15, and an indication for ICD implantation. BBP was attempted in twenty patients, others underwent RAAP. A Biotronik Selectra 3D 40-S sheath was used for BBP in patients in whom initial lead implantation was unsuccessful. BBP was defined based on P-wave morphology and fluoroscopic lead position. The RV lead was implanted in the RV apex in all patients and the AV delay was optimized based on diastolic filling period and E/e’. Devices were programmed in DDD mode. During follow up, diastolic function, functional capacity, atrial fibrillation, and heart failure hospitalisations were assessed in both groups. Results Among the forty patients (age 48.2+7.8 yrs, males 75%, ESC-SCD Risk 4.3+0.6%), the baseline P wave duration, E/A, E/e’ were 138.4+16.4 ms, 2.5+0.5, and 17.5+2.4, respectively. Six patients (15%) had a history of paroxysmal AF (3 each in BBP and RAAP groups). Of the 16 patients (80%) who underwent successful BBP, the Selectra 3D 40-S sheath was used in 8 patients (Figure 1, Panel A). During BBP, a bachmann bundle potential was recorded in 7 of 16 patients (43.8%) (Figure 1, Panel C). The pacing threshold (1.5+0.5@0.4ms vs. 0.9+0.3@0.4ms, p=0.026) was higher and the atrial sensing (1.8+0.4 vs. 3.3+0.6, p=0.002) was lower in the BBP group compared to the RAAP group at 4 weeks and 6 months of follow up. There was an acute rise in threshold (2.1@0.4 ms) in 1 BBP patient at 4 weeks of follow up. Patients in the BBP group had a reduction in P wave duration compared to the patients in the RAAP group (-22.5 + 5.4 vs. +5.6 + 3.2 ms, p&amp;lt;0.001). During follow up (11.4 + 3.4 months), there was a significant improvement in diastolic function (E/e’), functional capacity (NYHA Class) and reduction in NT-proBNP in the BBB group compared to the RAAP group (Figure 1). The percentage of atrial pacing was similar in both groups (BBP 73.2 + 7.8 vs. RAAP 78.5 + 9.1 %, p=0.219). The risk of atrial fibrillation/tachycardia (12.5% vs. 35.0%, p=0.022) and heart failure hospitalisations (6.3% vs. 20%, p=0.042) was lower in the BBP group compared with RAAP during follow up. Conclusions BBP is safe and effective in improving diastolic function, functional capacity and heart failure hospitalizations in patients with nHCM.BBP Pacing using Selectra 3D 40-S SheathChange in E/e', NYHA, and NT-pro BNP

Artificial Intelligence Applied to Electrical and Non-Invasive Hemodynamic Markers in Elderly Decompensated Chronic Heart Failure Patients.

The first aim of this study was to assess the predictive power of Tend interval (Te) and non-invasive hemodynamic markers, based on bioimpedance in decompensated chronic heart failure (CHF). The second one was to verify the possible differences in repolarization and hemodynamic data between CHF patients grouped by level of left ventricular ejection fraction (LVEF). Finally, we wanted to check if repolarization and hemodynamic data changed with clinical improvement or worsening in CHF patients. Two hundred and forty-three decompensated CHF patients were studied by 5 min ECG recordings to determine the mean and standard deviation (TeSD) of Te (first study). In a subgroup of 129 patients (second study), non-invasive hemodynamic and repolarization data were recorded for further evaluation. Total in-hospital and cardiovascular mortality rates were respectively 19 and 9%. Te was higher in the deceased than in surviving subjects (Te: 120 ± 28 vs. 100 ± 25 ms) and multivariable logistic regression analysis reported that Te was related to an increase of total (χ2: 35.45, odds ratio: 1.03, 95% confidence limit: 1.02-1.05, p < 0.001) and cardiovascular mortality (χ2: 32.58, odds ratio: 1.04, 95% confidence limit: 1.02-1.06, p < 0.001). Subjects with heart failure with reduced ejection fraction (HFrEF) reported higher levels of repolarization and lower non-invasive systolic hemodynamic data in comparison to those with preserved ejection fraction (HFpEF). In the subgroup, patients with the NT-proBNP reduction after therapy showed a lower rate of Te, heart rate, blood pressures, contractility index, and left ventricular ejection time in comparison with the patients without NT-proBNP reduction. Electrical signals from ECG and bioimpedance were capable of monitoring the patients with advanced decompensated CHF. These simple, inexpensive, non-invasive, easily repeatable, and transmissible markers could represent a tool to remotely monitor and to intercept the possible worsening of these patients early by machine learning and artificial intelligence tools.

Efficacy and Safety of Kuoxin Formula in the Treatment of Dilated Cardiomyopathy-Related Heart Failure: Study Protocol of a Randomized, Double-Blind, Placebo-Controlled, Multi-Center Clinical Trial.

Dilated cardiomyopathy (DCM) is a severe heterogeneous cardiomyopathy characterized by cardiac enlargement and declining heart function, often leading to refractory heart failure and life-threatening outcomes, particularly prevalent in China. The challenge lies in the scarcity of targeted therapies with substantial efficacy for DCM. Additionally, traditional anti-heart failure drugs are constrained due to hypotension propensity or limited symptom improvement. Kuoxin Formula (KXF), internally endorsed at Longhua Hospital, demonstrates clear biological evidence for enhancing cardiac function and myocardial remodeling. Previous clinical studies suggest its potential to enhance patients' quality of life. This trial aims to further evaluate KXF's safety and efficacy in managing DCM-related heart failure. This prospective, randomized, double-blind, placebo-controlled, multicenter trial aims to recruit 230 DCM patients from five centers. Participants will be randomly assigned to either KXF or placebo for 12 weeks, with careful monitoring of key indicators and adverse events. The primary outcome measures the proportion of patients with NT-proBNP reduction exceeding 30%. Secondary outcomes include New York Heart Association functional classification, Traditional Chinese Medicine syndrome scores, 6-minute walk test, Lee's heart failure score, and Minnesota Heart Failure Quality of Life Scale score. Ventricular remodeling will be assessed using cardiac ultrasound and ELISA. Safety metrics and adverse events will be meticulously recorded. This study will be the first multicentered research conducted in China that utilizes a randomized, double-blind, placebo-controlled design to investigate the use of TCM in the treatment of DCM. It seeks to develop new theoretical frameworks and provide solid clinical data to support the integration of TCM and modern medicine in treating heart failure in DCM patients. China Clinical Trial Registry, ChiCTR2300068937. Registered on March 1, 2023. https://www.chictr.org.cn/bin/project/edit?pid=190926.

Association of GDF15, NTpoBNP and PLGF with subclinical cardiac dysfunction in type 2 diabetes: effects of novel antidiabetic treatment

Abstract Background In type 2 diabetics, we investigated the effects of insulin, GLP-1Ra, SGLT-2i and their combination on blood biomarkers of cardiac function and their association with left ventricular and atrial function. Patients and methods A total of 200 diabetics (60.3±10.3-year-old) treated with metformin were randomized to insulin (n= 50), liraglutide (n=50), empagliflozin (n=50) or their combination (GLP-1RA+SGLT-2i) (n= 50) . We measured at baseline and 6 months post-treatment: (a) perfused boundary region of the sublingual arterial microvessels (marker of endothelial glycocalyx thickness), (b) pulse wave velocity (PWV), (c) Left Ventricular (LV) Global Longitudinal Strain (GLS) and Torsion, (d) LV Global Work Index (GWI), Global Constructive Work (GCW), Global Wasted Work (GWW), Global Work Efficiency (GWE), (e) Left atrial reservoir strain (LASr) and (f) Growth/Differentiation Factor-15 (GDF-15), NTproBNP, Placental Growth Factor (PLGF) as markers of cardiac dysfunction. Results Increasing GGDF-15 levels at baseline were related with increasing PWV (r=0.357, p&amp;lt;0.001). Moreover, increasing GDF-15 was related with reduced absolute GLS values (r=-0.425, p=0.005), increased LV Torsion (r=0.309, p=0.035), Twisting Velocity (r=0.345, p=0.018) and E/E’ (r=0.307, p=0.041) as well as reduced Untwisting velocity (r=-0.383, p=0.008) and LASr (r=-0,388, p=0.005). Increasing NTproBNP concentration at baseline was related with increasing PWV (r=0.445, p=0.001 and PBR5-25 (r=0.222, p=0.04) . Also, increasing NTroBNP was related with reduced absolute GLS (r=-0.454, p=0.002), LV GL strain rate (r=-0.360, p=0.008) , increased LV Torsion (r=0.329, p=0.029) and E/E’ (r=0.365, p=0.021). Increasing NTproBNP was also related with decreasing GWI (r=-0.471, p&amp;lt;0.001), GWE (r=-0.555, p&amp;lt;0.001), Untwisting velocity (r=-0.383, p=0.008) and LASr (r=-0,424, p=0.002). PLGF concentration at baseline was related with reduced absolute GLS (r=-0.341, p=0.012), LV GL strain rate (r=-0.302, p=0.008) and LASr (r=-0.321, p=0.036). At 6 months, the reduction of GDF-15 and NTproBNP levels was related with the respective reduction of PWV (p=0.022 and p=0.34) Furthermore, the reduction of NTproBNP at 6 months was related with an increase of GWI and GWE (r=0.455, p=0.006/ r=0.631, p=0.001,respectively). In patients treated with GLP-1RA, SGLT-2i and their combination, there was greater improvement of GLS, Torsion, Myocardial Work, LASr, NTproBNP, GDF-15 PLGF compared to patients treated with insulin (p&amp;lt;0.05) post-treatment. In patients treated with insulin, NTproBNP, GDF-15 and PLGF changes post-treatment were not related with the respective changes of the examined cardiac and vascular markers. Conclusion Elevated levels of GDF15, PLGF and NTproBNP are associated with cardiac and vascular dysfunction in patients with type 2 diabetics and their improvement after 6 months of treatment with GLP-1RA and /or SGLT2i is associated with improved cardiovascular function.

Inferior vena cava and lung ultrasound-guided therapy in acute heart failure (CAVAL US-AHF study): a randomized controlled trial

Abstract Background The 90-day readmission rate for hospitalized patients with acute heart failure (AHF) ranges from 25% to 30%, mostly due to persistent congestion at discharge. Since the optimal assessment of decongestion has not been clearly defined, there is an opportunity to implement new tools to identify subclinical congestion to guide treatment. Purpose To evaluate whether inferior vena cava (IVC) and pulmonary ultrasound (CAVAL US)-guided therapy in patients with AHF reduces subclinical congestion at discharge. A secondary objective was to investigate whether CAVAL US-guided therapy leads to improved outcomes al 90 days. Methods In this single-center, single-blind, randomized controlled trial, adult patients with AHF were randomized within 24 hours of hospital admission to the CAVAL US-guided strategy or clinically-guided decongestive therapy. A quantitative ultrasound protocol was used and patients were stratified into 3 groups according to the degree of congestion. All patients underwent lung and IVC ultrasound and were blinded to group allocation. The treating medical team was blinded to the results of the ultrasound evaluation in the control group and adjusted the treatments in the intervention group according to an individualized therapeutic algorithm. The primary endpoint was the presence of more than 5 B-lines and/or an increase in IVC diameter with and without collapsibility at discharge. The secondary endpoints were the composite of HF readmission, unplanned visit for worsening HF or death at 90 days and pro-B-type natriuretic peptide (NT-proBNP) reduction at discharge in %. Results Sixty patients were randomized to CAVAL US (n=30) or control (n=30). The mean age was 76.7±13 years, 68.3% were male and the mean left ventricular ejection fraction was 44% ± 15. The primary outcome occurred in 4 patients (13.3%) in the CAVAL US group and 20 patients (66.6%) in the control group (p&amp;lt;.001). A 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=0.038). Other secondary endpoints such as NT-proBNP reduction at discharge showed a non-statistically significant reduction in the CAVAL US group (48% IQR 27-67 vs 37% -3-59; p=0.09). The mean hospital stay was 4.5±5 days in the CAVAL US group and 3.3±1.6 days in the control group (p=0.26), with a trend toward higher total furosemide use in the CAVAL US group (170 mg IQR 120-240 vs 120 mg IQR 80-200, p=0.08). Safety outcomes were similar in both groups (p&amp;gt;0.05). Conclusion IVC and lung ultrasound-guided therapy in AHF patients significantly reduced subclinical congestion at discharge. CAVAL US-AHF provides evidence for the use of a simple, safe and non-invasive technique to guide decongestive therapy during hospitalization for AHF, that reduced the risk of HF readmission, unplanned visit for worsening HF, or death at 90 days without prolonging hospital stay.Subclinical congestion at dischargeKM secondary endpoint

Effects of treatment response on echocardiographic features among patients with light-chain cardiac amyloidosis

Abstract Background Complete response to treatment for light chain cardiac amyloidosis (AL-CA) may lead to improvement of myocardial function. The aim of this study was to evaluate the effect of treatment for AL-CA on echocardiographic characteristics of patients, and the prognostic impact of changes in longitudinal strain and myocardial work. Methods The study population comprised of sixty-one patients treated for AL between 2020 and 2022. All patients underwent comprehensive echocardiographic assessment including longitudinal strain and myocardial work imaging at baseline and at 1-year follow-up. Patients were stratified according to the depth of hematologic response to treatment for AL-CA as complete or not complete responders. The relationship between echocardiographic parameters and all-cause mortality was assessed by Kaplan Meir curves and cut-off points were selected using ROC analysis. Results A significant reduction in median NT-proBNP (from 2,771 to 1,486 pg/mL; p&amp;lt;0.001), posterior wall thickness (PWT) (from 13 to 12mm; p=0.002), and an increase in global work index (GWI) (from 1,115 to 1,356 mmHg%; p=0.018) was observed in all patients at 1-year follow up. After stratifying patients based on hematologic response to treatment, patients with complete response (CR) had a more pronounced decrease in intraventricular septum thickness (14.2 to 12.0mm; p=0.006), a trend towards improved global longitudinal strain (GLS) (-11.6 to -13.1%; p=0.064) and increased global constructive work (1,245 to 1,436 mmHg%; p=0.008), in addition to significant improvements in NT-proBNP, posterior wall thickness and global work index. Furthermore, the delta GLS (ρspearman=0.35; p&amp;lt;0.001) and delta GWI (ρspearman=-0.32; p=0.02) significantly correlated with delta NT-proBNP. Patients with GWI response, either any response or ROC-curve derived cut-off, had a better prognosis compared with patients without GWI response (log-rank p=0.043 and log-rank p=0.035, respectively). Conclusions Among patients treated for AL-CA, those with hematologic CR exhibited significant improvement in GWI and GWW. Additionally, our results indicate that GLS and GWI may have prognostic value in predicting survival among AL-CA patients and their changes correlate to NTproBNP decrease.

Abstract 15137: microRNA-132 Inhibition Improves Cardiac Function and Reduces Remodeling in Patients With Heart Failure With Reduced Ejection Fraction (HFrEF): An Exploratory Subgroup Analysis of the CDR132L First-in-Human Study

Background: The CDR132L first-in-human (FiH) study examined safety, tolerability, pharmacokinetic, and exploratory pharmacodynamic effects of different ascending doses of the novel antisense oligonucleotide CDR132L targeting microRNA-132-3p (miR-132) in patients with stable heart failure (HF) of ischemic origin receiving standard-of-care (n=28). The study population was not stratified according to their left-ventricular ejection fraction (LVEF), and therefore heterogenous, but equally distributed among heart failure with reduced or preserved ejection fraction (HFrEF or HFpEF). Research question: In an exploratory post-hoc analysis of pharmacodynamic parameters we specifically focused on patients with HFrEF (with a LVEF&lt;45% at baseline, n=14) and, based on our predictive PK/PD modeling, categorized patients into ‘non-pharmacodynamically active’ (non-PD active; placebo and 0.32 mg/kg CDR132L group) and 'pharmacodynamically active' (PD active; patients receiving 1, 3, or 10 mg/kg CDR132L). Results: The PD active group showed a significant median reduction in NT-proBNP by 37.1% between baseline and study endpoint (day 112) while this HF biomarker was increased by 17.7% in the non-PD active group (p=0.0152, Mann-Whitney U test). CDR132L treatment provoked a trend towards 6.1% improvement in LVEF. For the non-PD active group only +1.4% were noted. An additional biomarker related to HF and cardiac fibrosis, lipocalin-2 (NGAL), tended to decrease in the PD active, but not in the non-PD active group. Conclusion: Analysis of the HFrEF subgroup in this FiH trial, although limited by the small patient numbers, indicatively underlines the encouraging benefits of CDR132L, a novel antisense drug, on LV function and cardiac remodeling as established in previous large animal HF models.

Reduced Early Mortality with Daratumumab-Based Frontline Therapy in Systemic AL Amyloidosis- Experience from the Columbia Amyloidosis Multidisciplinary Program

Introduction: Despite advances in treatmentof systemic light chain (AL) amyloidosis, early mortality (EM) has been substantial up until recently, with a 6-month EM rate of approximately 25% in the era preceding daratumumab (Muchtar et al. Blood. 2017).Daratumumab in combination with bortezomib, cyclophosphamide and dexamethasone (Dara-VCD) is the first FDA-approved therapy for systemic AL amyloidosis based on the ANDROMEDA trial with an unprecedented hematologic complete response (Heme-CR) rate ≈ 50%. However, data on hematologic and cardiac organ response rate and estimated early mortality (EM) in different stages since routine introduction of daratumumab-based frontline therapy are lacking. Methods: We performed a retrospective cohort study of all consecutive patients treated with daratumumab-based combination therapy at Columbia Amyloidosis Multidisciplinary Program (CAMP). Hematologic and cardiac organ response rates are reported on an intention-to-treat (ITT) basis, with patients who died prior to response evaluation or those with missing data classified as non-responders. Time-to-event analyses were performed by the Kaplan-Meier method. Results: Eighty-three consecutive patients treated with daratumumab-based frontline therapy were included in the analysis. The baseline characteristics of our cohort in comparison with Dara-VCD arm of ANDROMEDA is shown in Table 1. The median age at diagnosis was 68 years (range, 40-91), with 65% being males and 13 patients (16%) of Black/African-American race. The median dFLC (involved - uninvolved) was 21.9 mg/dl, with 61% of patients having baseline dFLC&amp;gt;18 mg/dl. Mayo 2004 stage IIIa/IIIb comprised 65% of our cohort compared to 37% of ANDROMEDA trial. Thirty-three patients (44%) had NYHA Class III/IV symptoms. The daratumumab-based frontline regimens used were Dara-VCD (n=78), Dara-VD (n=2), Dara-D (n=2), and Dara-Ixazomib-D (n=1). High-dose melphalan followed by autologous hematopoietic cell transplantation (HDM-AHCT) as a part of frontline therapy was performed in 11 patients (13.4%), with melphalan dose being 140 mg/m 2 in 8, 200 mg/m2 in 2, and 100 mg/m 2 in 1 patient. Hematologic response was evaluable in 78 patients (i.e. dFLC&amp;gt;2 mg/dl at diagnosis). On an ITT basis, Heme-CR was achieved by 39 patients (50%), and very good partial response or better (Heme ≥VGPR) by 57 patients (73.1%). The median time to Heme-CR from treatment initiation was 2.7 months (range, 0.42-13.97). Among patients evaluable for cardiac organ response (i.e. NT-proBNP≥650 pg/ml; n=64), 35 (58.3%) achieved an organ response. The median time to initial cardiac response (&amp;gt;30% reduction in NT pro-BNP with absolute reduction of &amp;gt;300 pg/ml) was 2.95 months (range, 0.43-10.43). Figure 1 demonstrates comparable hematologic and numerically higher cardiac organ response rate in our cohort vs Dara-VCD arm of ANDROMEDA trial. Next, we estimated the EM rate. The estimated EM at 6 months in our cohort was 7.6% (95% CI, 3.4-15.9). 6-month EM in patients with Mayo 2004 stage IIIb was 22.2% (95% CI, 9.5-43.6) vs 1.96% (95% CI, 0.27-12.65) in those with stage I-IIIa ( p&amp;lt;0.001) [Figure 2]. By Mayo 2012 staging, the estimated 6-month EM rate in patients with stage I, II, III, and IV disease was 0% (95% CI, 0-0), 0% (95% CI, 0-0), 9.6% (95% CI, 2.4-31.3), and 12.9% (95% CI, 4.9-29.8) respectively ( p=0.0425). Among patients who underwent upfront HDM-AHCT (n=11), there was no transplant-related mortality at 100 days. On evaluating the prognostic impact of individual factors in Mayo 2012 staging (NT-proBNP, Troponin, and dFLC) on OS, dFLC&amp;gt;18 mg/dl was no longer a significant adverse prognostic factor for survival in both univariate and multivariate analysis. Updated data will be presented at the meeting. Conclusion: Despite a sicker population with more advanced cardiac involvement compared to ANDROMEDA trial, daratumumab-based frontline induction therapy led to similar Heme-CR rate and favorable cardiac organ response rate in our cohort. Additionally, estimated 6-month EM has decreased by approximately 3-fold compared to historical data, with dramatic reduction in Mayo 2004 stage I-IIIa and continued substantial EM in stage IIIb disease. Finally, as clone-directed therapy has significantly improved, light chain burden at baseline may not be a relevant prognostic factor in contemporary era and should be scrutinized in larger datasets to re-design the staging system.

The potential of sodium-glucose cotransporter 2 inhibitors for the treatment of systemic right ventricular failure in adults with congenital heart disease.

Given the compelling evidence on the effectiveness of sodium-glucose cotransporter 2 inhibitors (SGLT2i) in the conventional heart failure population, SGLT2i deserve exploration in systemic right ventricular (sRV) failure. The initial experience with dapagliflozin in sRV failure patients is described, with a focus on tolerability and short-term effects on clinical outcomes. Ten patients (70% female, median age 50 years [46.5-52]) with symptomatic sRV failure who received dapagliflozin 10 mg per day on top of optimal medical therapy between 04-2021 and 01-2023 were included. Within 4 weeks, no significant changes in blood pressure, electrolytes, or serum glucose occurred. Creatinine and estimated glomerular filtration rate (eGFR) showed a slight decline (88 ± 17 to 97 ± 23 µmol/L, p = 0.036, and 72 ± 14 vs. 66 ± 16 ml/min/1.73m2, p = 0.020, respectively). At 6 months follow-up (n = 8), median NT-proBNP decreased significantly from 736.6 [589.3-1193.3] to 531.6 [400.8-1018] ng/L (p = 0.012). Creatinine and eGFR recovered to baseline levels. There were no significant changes in echocardiographic systolic sRV or left ventricular function. New York Heart Association class improved significantly in 4 out of 8 patients (p = 0.046), who also showed an improvement in the 6-minute walk test or bicycle exercise test performance. One female patient developed an uncomplicated urinary tract infection. No patients discontinued treatment. Dapagliflozin was well-tolerated in this small cohort of sRV failure patients. While the early results on the reduction of NT-proBNP and clinical outcome parameters are encouraging, large-scale prospective studies are warranted to thoroughly evaluate the effects of SGLT2i in the growing sRV failure population.

Early glomerular filtration rates changes and risk of mortality in acute heart failure. The modifying role of admission renal function and decongestion

BackgroundThe pathophysiology of changes in estimated glomerular filtration rate (eGFR) in acute heart failure (AHF) is complex and multifactorial. We evaluated the associated mortality risk of early changes in eGFR across baseline renal function on admission and early changes in natriuretic peptides in patients admitted with AHF. MethodsWe retrospectively evaluated 2,070 patients admitted with AHF. Renal dysfunction on admission was defined as eGFR<60 ml/min/1.73m2 and successful decongestion as NT-proBNP decreased >30% from baseline. We assessed the mortality risk associated with eGFR changes from baseline at 48–72 h after admission (ΔeGFR%) according to baseline renal function, and NT-proBNP changes at 48–72 h through Cox regression analyses. ResultsThe mean age was 74.4 ± 11.2 years, and 930 (44.9%) were women. The proportion of admission eGFR<60 ml/min/1.73m2 and 48–72 h changes in NT-proBNP>30% were 50.5% and 32.8%, respectively. At a median follow-up of 1.75 years, 928 deaths were registered. In the whole sample, changes in renal function were not associated with mortality (p = 0.208). The adjusted analysis revealed that the risk of mortality related to ΔeGFR% was heterogeneous across baseline renal function and changes in NT-proBNP (p-value for interaction=0.003). ΔeGFR% was not associated with mortality in patients with baseline eGFR≥60 ml/min/1.73m2. In those with eGFR<60 ml/min/1.73m2, a decrease in eGFR was associated with higher mortality, particularly in those with a reduction in NT-proBNP<30%. ConclusionIn patients with AHF, early ΔeGFR% was associated with the risk of long-term mortality only in patients with renal dysfunction on admission and no early decline in NT-proBNP.

Treatment effects of pulmonary artery denervation for pulmonary arterial hypertension stratified by REVEAL risk score: Results from PADN-CFDA trial

The differential treatment effect of pulmonary artery denervation (PADN) in pulmonary arterial hypertension (PAH) patients with different risk burdens remains unclear. This study aimed to determine the effectiveness of PADN in low vs intermediate-high-risk PAH patients. In total, 128 patients with treatment naive PAH included in the PADN-CFDA trial were categorized into low-risk and intermediate-high-risk patients. The primary endpoint was the between-group difference in the change in 6-min walk distance (6 MWD) from baseline to 6 months. In the intermediate-high-risk group, those treated with PADN and PDE-5i had a greater improvement in 6 MWD from baseline to 6 months as compared to those treated with sham plus PDE-5i. From baseline to 6 months, pulmonary vascular resistance (PVR) was reduced by -6.1 ± 0.6 and -2.0 ± 0.7 Wood units following PADN plus PDE-5i and sham plus PDE-5i, respectively, along with the significant reduction of NT-proBNP in the intermediate-high-risk group. However, there were no significant differences in 6 MWD, PVR, and NT-proBNP between the PADN plus PDE-5i and sham plus PDE-5i groups among low-risk patients. Moreover, the right ventricular function was equally improved by PADN treatment across the low-, intermediate-, and high-risk groups. Clinical worsening was less with PADN plus PDE-5i treatment during the 6-month follow-up. In patients with pulmonary arterial hypertension, pulmonary artery denervation plus PDE-5i improved exercise capacity, NT-proBNP, hemodynamic, and clinical outcomes during the 6-month follow-up among intermediate-high risk patients.

Combined Left Ventricular Ejection Fraction and N-Terminal pro-B-type Natriuretic Peptide after Sacubitril/Valsartan for Predicting Outcomes in Patients with Heart Failure with Reduced Ejection Fraction.

The aim of this study was to determine whether a combined increase of ≥ 10% in left ventricular ejection fraction (LVEF) and decrease in N-terminal pro-B-type natriuretic peptide (NT pro-BNP) to < 1000 pg/mL after treatment with sacubitril/valsartan (SAC/VAL) in patients with heart failure with reduced ejection fraction (HFrEF) translated to better treatment outcomes in a real-world Taiwanese population. This is a single-center, prospective, non-randomized, observational study. Consecutive patients with HFrEF were treated with SAC/VAL and followed up for at least 12 months. The primary endpoint was a change in LVEF and reduction in NT pro-BNP at 12 months. The secondary outcomes were death and heart failure (HF) rehospitalization. A total of 105 patients were analyzed after 12 months of SAC/VAL treatment. The mean age was 66.0 ± 11.6 years, and the mean LVEF and NT pro-BNP were 33.6 ± 6.7% and 4462.7 ± 5851.7 pg/mL respectively. The mean LVEF significantly increased to 50.5 ± 10.3% (p < 0.001), while NT pro-BNP decreased to 1270.3 ± 2368.2 pg/mL (p = 0.001) at 12 months, with the greatest changes occurring in the first 3 months of treatment (p < 0.001). Five patients died and 12 were rehospitalized for HF. None of the patients in the responder group died compared to 5 deaths in the non-responder group (p = 0.039). Combined ≥ 10% LVEF increase and NT pro-BNP of < 1000 pg/mL was an independent predictor of death and HF rehospitalization (p = 0.019). SAC/VAL treatment resulted in significant improvements in LVEF, reduced NT pro-BNP level, death and HF hospitalization. Taken separately, an NT pro-BNP level of < 1000 pg/mL was a better predictor than ≥ 10% LVEF increase. Combining both variables predicted fewer deaths and HF rehospitalizations. Even with failure to reach the target dose, SAC/VAL still had significantly beneficial treatment outcomes in Taiwanese patients.

Novel Approach for Assessing Postinfarct Myocardial Injury and Inflammation Using Hybrid Somatostatin Receptor Positron Emission Tomography/Magnetic Resonance Imaging.

Novel Approach for Assessing Postinfarct Myocardial Injury and Inflammation Using Hybrid Somatostatin Receptor Positron Emission Tomography/Magnetic Resonance Imaging.

Early Administration of Sacubitril/Valsartan is Associated with more Rapid NT-proBNP Recovery in High-Risk Patients Hospitalized for Acute Heart Failure

BACKGROUND: in patients hospitalized for heart failure with reduced ejection fraction (HFrEF), randomized controlled trials have demonstrated some advantages in starting sacubitril/valsartan before discharge. However, information about the effects of sacubitril/valsartan use in the acute phase of HfrEF hospitalizations is limited. AIM: To evaluate clinical, biomarker, and echocardiographic effects of starting sacubitril/valsartan in real-world HFrEF patients before discharge. METHODS: retrospective analysis of 124 consecutive patients (58.9% males, 75.6±11.4 years) hospitalized for HFrEF. In 36, sacubitril/valsartan was started before discharge (Group A); in the remaining 88, at the 1-month follow-up visit (Group B). The primary endpoint was time-averaged NT-proBNP level reduction from admission to discharge. RESULTS: Group A showed a worse baseline clinical risk profile (diabetes: 47.2 vs. 20.7%, p=0.007; coronary artery disease: 66.7 vs. 22.7%, p&lt;0.001; systolic blood pressure: 118.0±20.8 vs. 132.9±22.9 mmHg, p=0.001; left ventricular ejection fraction: 28.5±5.5 vs. 32.1±7.6%, p&lt;0.0004). Nevertheless, the time-averaged mean NT-proBNP reduction was significantly higher in group A patients (ratio of change -0.30, 95% CI -0.40 to -0.21, &lt;0.0001 vs. group B). Creatinine and K+ levels did not change significantly during the hospital stay. Multivariate analysis suggested diabetes, coronary artery disease, higher systolic blood pressure, and the need for inotropic support as independent predictors for in-hospital sacubitril/valsartan treatment. CONCLUSIONS: in real-world patients, starting sacubitril/valsartan in-hospital rather than waiting for further stabilization was associated with a more considerable reduction of NT-proBNP levels at discharge, with an excellent safety profile. These data confirm randomized trials results, extending them to higher-risk real-world HFrEF patients.