Baseline Brain Natriuretic Peptide Research Articles

Identifying heart failure dynamics using multi-point electrocardiograms and deep learning

Abstract Background Heart failure (HF) hospitalizations are related to poor survival outcomes, emphasizing the need for early detection and intervention. Recent studies have reported the potential of deep learning algorithms in identifying heart failure through electrocardiogram (ECG) with notable accuracy. However, evidence supporting their utility in the ongoing monitoring and follow-up of HF patients remains uncertain. Advanced diagnostic tools that can effectively track heart failure progression or improvement over time are needed. Purpose To address this challenge, we developed a deep learning model analyzing 12-lead ECG waveforms at two time points, aiming to detect HF deterioration or improvement, potentially revolutionizing HF management. Methods This study analyzed 32,045 ECGs from 6,892 unique adult patients (aged 18 years and older) visiting the Department of Cardiology at Kobe University Hospital. The participants were randomly assigned to training (4,284 patients), validation (1,034 patients), and test (1,034 patients) datasets. ElecTransformer was developed to classify HF status into deteriorated, improved, and no change classes based on ECG waveform signals at two different time points and to estimate brain natriuretic peptide (BNP) levels. Performance metrics, such as the area under the receiver operating characteristic curve (AUROC) and accuracy, were calculated, and attention mapping via gradient-weighted class activation mapping was utilized to interpret the model's decision-making ability. Results The patients had an average age of 65 years (±15.4 years) and BNP levels averaged 71.5 pg/mL (25.8 to 185.2 pg/mL). For HF status classification, ElecTransformer achieved an AUROC of 0.845 and an accuracy of 0.821, improving to an AUROC of 0.885 and an accuracy of 0.833 with baseline BNP integration. The ElecTransformer accurately estimated BNP levels from ECG data, evidenced by a correlation coefficient of 0.798. Averaged attention mapping showed that the QRS complex was the most important feature for determining model outputs with lesser effects seen for P waves and T waves variance Conclusions Harnessing a Transformer-based deep learning model to analyze multiple ECGs markedly improves the accuracy in detecting changes in heart failure status. This method offers a valuable non-invasive option for monitoring heart failure progression, potentially leading to better patient management and earlier intervention in heart failure treatment.Architecture and Performance of ModelsAveraged attention mapping

Diagnostic accuracy of baseline troponin and troponin change for the diagnosis of myocardial infarction complicated with heart failure

BackgroundThe diagnosis of myocardial infarction (MI) in the presence of heart failure (HF) presents a clinical problem. While diagnostic algorithms using high-sensitivity cardiac troponin have been established for suspected MI,...

Clinical Utility of Baseline Brain Natriuretic Peptide Levels on Health Status Outcomes after Catheter Ablation for Atrial Fibrillation in Individuals without Heart Failure.

Catheter ablation (CA) benefits atrial fibrillation (AF) patients with heart failure (HF). Brain natriuretic peptide (BNP), a marker of left-ventricular pressure load, may serve as a potential surrogate for predicting quality of life (QOL) in a broader range of patients. Within the multicenter KiCS-AF registry, 491 AF patients underwent CA without clinical HF (e.g., documented history of HF, left ventricular ejection fraction ≤ 40%, or BNP levels ≥ 100 pg/mL). Participants, aged 61 ± 10 years, were categorized by baseline BNP quartiles. Atrial Fibrillation Effect on QualiTy-of-Life (AFEQT) questionnaire assessments were assessed at baseline and 1 year. A lower baseline BNP correlated with reduced AFEQT scores. Post CA, all groups showed significant AFEQT score improvements. The lower-BNP group displayed notable enhancements (18.2 ± 1.2, 15.0 ± 1.1, 12.6 ± 1.2, 13.6 ± 1.2, p < 0.005), especially in symptom and treatment concern areas. Even those with normal BNP levels (≤18.4 pg/mL) exhibited significant QOL improvements. Comparing paroxysmal AF (PAF) and non-PAF groups, the PAF group, especially with higher BNP levels, showed greater AFEQT score improvements. This study establishes BNP as a predictive marker for QOL enhancement in non-HF patients undergoing CA for AF. BNP levels represent AF stages, with individuals in earlier stages, especially within normal BNP levels, experiencing greater QOL improvements.

Abstract 16432: Screening for Cardiovascular Complications in Pediatric Hematopoietic Stem Cell Transplant Patients

Introduction: Hematopoietic stem cell transplantation (HSCT) carries a risk of cardiovascular morbidity, with reported incidences of pericardial effusion, pulmonary hypertension (PH), and reduced left ventricular ejection fraction (LVEF). Screening for cardiovascular complications in children undergoing HSCT may be essential, but its utility remains unexplored. Hypothesis: Screening HSCT children using echocardiography and brain natriuretic peptide (BNP) can detect cardiovascular complications associated with adverse outcomes in this population. Methods: This prospective single-center cohort study analyzed children undergoing HSCT over a 2-year period. Baseline, 7-day, and 30-day echocardiograms and BNP levels were obtained. Multilevel linear regression assessed changes in echocardiograms and BNP. Logistic regression determined associations between cardiac complications and outcomes. Results: The study included 43 patients, with a median age of 8.6 years (IQR 3.7, 14.6). Echocardiograms were obtained at baseline (n=43), day+7 (n=34), and day+30 (n=25). BNP levels were obtained at baseline (n=41), day+7 (n=34), and day+30 (n=12). Adverse outcomes included TMA (n=7), endothelial dysfunction (n=36), mechanical ventilation (n=8), and death (n=8). Pericardial effusion was the most common finding (n=2(6%) at day+7, n=4(16%) at day+30). Pericardial effusion at either day+7 or day+30 predicted death (OR 15.7, 95% CI 1.8-137, p=0.013) and TMA (OR 13.1, 95% CI 1.7-103, p=0.014). A 10% decrease in LVEF was observed in 6 (17%) of patients at day+7 and 2 (8%) at day+30, and was associated with reduced mortality (OR 0.1, 95% CI 0-0.6, p=0.009). The change in BNP level at day+7 was 7pg/mL (IQR 6, 66) and 5pg/mL (IQR 3, 20) at day+30. A 10 point increase in BNP carried an increased risk of endothelial dysfunction (OR 4.1, 95% CI 1.3-263, p&lt;0.001). No patients developed PH. Conclusions: Cardiovascular complications are common after HSCT in children and carry diagnostic and prognostic significance. Further refinement of the screening protocol is necessary to determine the optimal timing of testing and assess its clinical utility.

Invasive Hemodynamic and Vasoreactivity Testing with Inhaled Iloprost in Children with Pulmonary Arterial Hypertension Associated with Congenital Heart Defects

Objective: Invasive hemodynamic evaluation and acute vasoreactivity testing are recommended in the diagnosis of pulmonary arterial hypertension (PAH), but their clinical role in children with PAH associated with congenital heart defects (CHD) is unclear. This study aims to investigate acute hemodynamic responses to inhaled iloprost, and its role in prognosis in children with PAH-CHD. Methods: A retrospective analysis was conducted on 83 pediatric patients with PAH-CHD in whom invasive hemodynamics were evaluated before and after a single inhaled dose of iloprost at a single center between 2010 and 2022. Details of the CHD corrective operation, medical treatment, and outcome for each patient were obtained via medical records or telephone contact. A composite endpoint of all-cause death, admission for worsening heart failure during follow-up, and event-free survival was defined, and risk factors associated with this composite endpoint were analyzed. Results: The patient age was (11.3 ± 4.6) years, and 60 (72.3%) were female. Fifty-nine (71.1%) patients were diagnosed with Eisenmenger syndrome. After iloprost inhalation, mean pulmonary artery pressure decreased from (78.2 ± 11.5) to (72.3 ± 13.2) mmHg (P &lt; 0.001), and pulmonary vascular resistance index (PVRI) decreased from (18.0 ± 7.9) to (14.5 ± 8.1) WU·m2 (P &lt; 0.001). A total of 38 (45.8%) patients had a positive response, defined as a PVRI decrease &gt;25% with stable systemic pressure. Thirty-seven (44.6%) patients underwent a corrective CHD operation at a median of 24 d after hemodynamic evaluation. Nine patients died, and 15 met the composite endpoint during a follow-up period of 5.4 (3.8, 8.8) years. Five-year event-free survival estimates were 96.7% (95% confidence interval: 90.3%–100%) in patients with a positive response, and 82.8% (95% confidence interval: 71.7%–94.5%) in patients with a non-positive response (log-rank P = 0.012). A positive PVRI response and higher pulmonary arterial oxygen saturation after iloprost inhalation, lower baseline brain natriuretic peptide, and PAH-targeted therapy at follow-up were significantly associated with a favorable clinical outcome. A positive acute vasoreactivity testing response and PAH-targeted therapy at follow-up were independent predictors of outcome in multivariate Cox analysis. Conclusions: Acute inhalation of iloprost can lead to a significant decrease in hemodynamic parameters. Responsiveness to inhaled iloprost is associated with better outcomes and can be a valuable predictor of outcomes.

Serum cholesterol levels and the risk of brain natriuretic peptide-diagnosed heart failure in postmenopausal women: a population-based prospective cohort study.

Hormonal changes during menopause can disturb serum cholesterol which is closely associated with cardiovascular disease. This study investigated the prospective association between serum cholesterol and heart failure (HF) risk in postmenopausal women. We analyzed data from 1,307 Japanese women, aged 55 to 94 years. All women had no history of HF, and their baseline brain natriuretic peptide (BNP) levels were less than 100 pg/mL. During the follow-ups conducted every 2 years, HF was diagnosed among women who developed BNP of 100 pg/mL or greater. Cox proportional hazard models were applied to calculate hazard ratios and 95% CI of HF for women per their baseline total cholesterol, low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol (HDL-C) levels. The Cox regression models were adjusted for age, body mass index, smoking, alcohol drinking, hypertension, diabetes, cardiac murmurs, arrhythmia, stroke or ischemic heart disease, chronic kidney disease, and lipid-lowering agent use. Within an 8-year median follow-up, 153 participants developed HF. In the multivariable-adjusted model, women with total cholesterol of 240 mg/dL or greater (compared with 160-199 mg/dL) and HDL-C of 100 mg/dL or greater (compared with 50-59 mg/dL) showed an increased risk of HF: hazard ratios (95% CI) = 1.70 (1.04-2.77) and 2.70 (1.10-6.64), respectively. The results remained significant after further adjusting for baseline BNP. No associations were observed with low-density lipoprotein cholesterol. Total cholesterol of 240 mg/dL or greater and HDL-C of 100 mg/dL or greater were positively associated with the risk of HF in postmenopausal Japanese women.

Baseline natriuretic peptides as a predictor of atrial fibrillation recurrence after radiofrequency-based pulmonary vein isolation in a non-heart failure population: A subanalysis from DECAAF II.

Brain natriuretic peptide (BNP) is a marker of myocardial stretch and may have prognostic significance in patients with atrial fibrillation (AF) without heart failure (HF). We investigated the association between baseline BNP levels and arrhythmia recurrence following pulmonary vein isolation (PVI) among patients with persistent AF without HF. We analyzed 125 patients with persistent AF without HF who had baseline BNP measured from the DECAAF II trial. The primary outcome was arrhythmia recurrence following ablation. The baseline characteristics across the two groups were compared using Chi-square test and Wilcoxon rank test accordingly. Cox regression analysis was used to analyze the association between baseline BNP levels and the primary outcome. Across the entire cohort, 64 (51%) patients experienced arrhythmia recurrence. When comparing patients who experienced arrythmia recurrence to patients who did not, patients with recurrent arrhythmia had higher levels of pre-ablation BNP, as evidenced by differences in means (330.05pg/mL) compared to patients without recurrent arrhythmia (182.39 pg/mL) (p<.05). A cut-off BNP value of 300pg/mL provided the largest area under curve (AUC) of receiver-operating characteristic (ROC) curve on univariate logistic regression. On unadjusted Cox analysis, for every 100 unit increase in BNP, the hazard ratio for the primary outcome increased 1.09 (1.026-1.158) times (p=.004). After adjusting for sex, hypertension, and stroke, the results remained significant (HR=1.8516, CI 95% [1.0139 - 3.381], p=.045). In the non-heart failure population, BNP levels predict AF recurrence following PVI in persistent AF patients.

Relationship between coronary blood flow and improvement of cardiac function after catheter ablation for persistent atrial fibrillation.

The relationship between coronary blood flow during atrial fibrillation (AF) and improvement of cardiac function after catheter ablation (CA) for persistent AF (PeAF) is not prominent; this study was conducted to evaluate this relationship. This was a retrospective case-control study. Eighty-five patients with PeAF (resting heart rate < 100bpm) and heart failure with reduced ejection fraction (left ventricular ejection fraction (LVEF) < 40%) who had undergone coronary angiography within 1week before CA were included. All patients could maintain a sinus rhythm for > 6months after CA. The primary outcome was improvement of cardiac function with an LVEF cutoff value of > 50% during sinus rhythm 6months after CA. In the LVEF improvement group (N = 57), patients were younger, with a higher baseline diastolic blood pressure and lower baseline brain natriuretic peptide level than the no LVEF improvement group (N = 28). Heart rate at baseline and 6months after CA and AF duration did not differ between the two groups. Thrombolysis in myocardial infarction frame count parameters was significantly higher in the LVEF improvement (P < 0.001) than in the no LVEF improvement group. Multivariate logistic regression analysis revealed mean thrombolysis in myocardial infarction frame count as an independent factor for LVEF improvement (odds ratio, 1.72 (95% confidence interval 1.17-2.54); P = 0.006). Coronary blood flow in patients with PeAF is strongly associated with improved left ventricular systolic function after the restoration of sinus rhythm by CA for PeAF and heart failure with reduced ejection fraction.

Analysis Of Clinical, Biochemical And Echocardiographic Criteria For Heart Failure With Preserved Ejection Fraction

Introduction Heart failure with preserved ejection fraction (HFpEF) is on pace to become the most common type of heart failure in the population with a prevalence that is increasing by 1% annually. Despite this, there remains no gold standard in diagnosing HFpEF. In addition to clinical exam and history, scoring criteria including H2FPEF score and HFA-PEFF score have been validated to assist in diagnosis. Guidelines and algorithms to determine echocardiographic diastolic dysfunction have also been described. Purpose Our study aimed to compare the sensitivities of various clinical, biochemical and echocardiographic criteria used to diagnosis HFpEF on a cohort of admitted HFpEF patients. Methods: This was a single-center retrospective review of inpatients with a primary diagnosis of HFpEF over a 2-year period. Electronic medical records were reviewed to analyze patient demographics, medical comorbidities and laboratory results. Echocardiograms were reviewed to analyze left ventricular mass, left atrial volume index and tricuspid regurgitation jet velocity as well as parameters of diastology to determine H2FPEF, HFA-PEFF scores, and American Society of Echocardiography diastolic dysfunction (ASE-DD) grading. Sensitivities for various diagnostic criteria were compared. A subgroup analysis was performed for different cut-offs of E/e’ septal velocities. Student's T test was performed for continuous data and statistical significant was defined as p<0.05. Results Over a 2 year period, 325 patients admitted with a primary diagnosis of HFpEF were analyzed. The average patient age was 80.2 years and 197 patients were female (60.6%). Brain natriuretic peptide (BNP) great than 100 pg/ml had the highest sensitivity of 94%. ASE-DD criteria for diastolic dysfunction had a sensitivity of 58%. H2FPEF risk percentage of ≥90% had sensitivity of 63%. Septal E/e’ of ≥15 had a sensitivity of 57% which increased to 90% when cut-off was lowered to ≥10. In a subgroup analysis of E/e’ <12 or ≥12, patients with E/e' ≥12 had significantly higher H2FPEF score, HFA-PEFF score and length of stay (p<0.05). Average E/e’ also had a positive correlation to percent change in BNP from baseline (R=0.83) and admission BNP (R=0.62). Conclusion Our study shows that current diagnostic criteria for HFpEF have relatively low sensitivity. Specifically, echocardiographic criteria may be too strict and a lower E/e’ cutoff may improve diagnostic sensitivity. The correlation of E/e’ and BNP suggests a relationship between the functional and biochemical entities of HFpEF. Further studies to optimize HFpEF diagnostic criteria are desired. Heart failure with preserved ejection fraction (HFpEF) is on pace to become the most common type of heart failure in the population with a prevalence that is increasing by 1% annually. Despite this, there remains no gold standard in diagnosing HFpEF. In addition to clinical exam and history, scoring criteria including H2FPEF score and HFA-PEFF score have been validated to assist in diagnosis. Guidelines and algorithms to determine echocardiographic diastolic dysfunction have also been described. Our study aimed to compare the sensitivities of various clinical, biochemical and echocardiographic criteria used to diagnosis HFpEF on a cohort of admitted HFpEF patients. Methods: This was a single-center retrospective review of inpatients with a primary diagnosis of HFpEF over a 2-year period. Electronic medical records were reviewed to analyze patient demographics, medical comorbidities and laboratory results. Echocardiograms were reviewed to analyze left ventricular mass, left atrial volume index and tricuspid regurgitation jet velocity as well as parameters of diastology to determine H2FPEF, HFA-PEFF scores, and American Society of Echocardiography diastolic dysfunction (ASE-DD) grading. Sensitivities for various diagnostic criteria were compared. A subgroup analysis was performed for different cut-offs of E/e’ septal velocities. Student's T test was performed for continuous data and statistical significant was defined as p<0.05. Over a 2 year period, 325 patients admitted with a primary diagnosis of HFpEF were analyzed. The average patient age was 80.2 years and 197 patients were female (60.6%). Brain natriuretic peptide (BNP) great than 100 pg/ml had the highest sensitivity of 94%. ASE-DD criteria for diastolic dysfunction had a sensitivity of 58%. H2FPEF risk percentage of ≥90% had sensitivity of 63%. Septal E/e’ of ≥15 had a sensitivity of 57% which increased to 90% when cut-off was lowered to ≥10. In a subgroup analysis of E/e’ <12 or ≥12, patients with E/e' ≥12 had significantly higher H2FPEF score, HFA-PEFF score and length of stay (p<0.05). Average E/e’ also had a positive correlation to percent change in BNP from baseline (R=0.83) and admission BNP (R=0.62). Our study shows that current diagnostic criteria for HFpEF have relatively low sensitivity. Specifically, echocardiographic criteria may be too strict and a lower E/e’ cutoff may improve diagnostic sensitivity. The correlation of E/e’ and BNP suggests a relationship between the functional and biochemical entities of HFpEF. Further studies to optimize HFpEF diagnostic criteria are desired.

Outcomes of radiofrequency catheter ablation for persistent and long-standing persistent atrial fibrillation

Abstract Introduction Catheter ablation has become the first-line treatment for symptomatic patients with atrial fibrillation (AF). Several approaches of substrate ablation have been used for persistent and long-standing persistent AF and the best protocol procedure is yet to be established. The purpose of this study was to evaluate the outcomes of patients submitted to catheter ablation of persistent and long-standing persistent AF adding extra-pulmonary substrate approaches to pulmonary vein isolation. Methods We retrospectively studied 67 consecutive patients referred for the first procedure of catheter ablation of persistent or long-standing persistent AF from May 2016 to October 2018. The first 27 patients were subjected to pulmonary vein isolation and complex fractionated atrial electrograms (CFAE) ablation (group 1) and the last 40 patients were subjected to a tailored approach guided by voltage map areas and CFAE (group 2). Patient characteristics, procedure details and follow-up were assessed, and predictors of recurrence were determined. Results Mean age was 59±11 years with 58% being male. During a mean follow-up of 16±6 months 27% of the patients showed AF recurrence. There were no differences in baseline characteristics of group 1 and 2. A higher recurrence rate was found in group 1 by comparison with group 2 (40.7% vs 17.5%, Log Rank X2 = 5.076, P=0.024) (Figure 1). Also, recurrence was associated with a longer AF duration, an increased baseline Brain Natriuretic Peptide (BNP), an increased left atrium (LA) volume, the presence of hyperthyroidism, the absence of sinus rhythm after procedure, the inducibility of AF post-ablation and the absence of an antiarrhythmic drug at hospital discharge. After adjustment for other confounders, the patient group (HR 5.16 [1.23–21.71] P=0.025), a long-standing AF (HR 9.09 [1.41–58.82] P=0.020), the BNP value at admission (HR 1.03 [1.01–1.05] P=0.033) and the LA volume index (HR 1.13 [1.02–1.25] P=0.017) were the only independent predictors of recurrence. Conclusion Ablation of persistent and long-standing persistent AF is feasible with good results when a substrate approach is added to pulmonary vein isolation. A tailored approach seems to be more efficient, showing best outcomes in mid-term follow-up. A long-standing AF, higher BNP value and the LA enlargement are important predictors of recurrence and should be used to better select patients and to manage follow-up. Funding Acknowledgement Type of funding sources: None.

Improving risk stratifcation of pulmonary hypertension patients

Abstract Background According to the 2016 ESC/ERS Guidelines on Pulmonary Hypertension (PH), the right atrial area (RAA) and the presence ofa pericardial effusion (PE) are the two main echocardiographic prognostic markers in PH patients (pts). Aim To assess the predictive ability of these two parameters. Methods Pts with PH were prospectively studied and several clinical/demographic/echocardiographic were retrieved as well as data from six-minute walk test (6MWT) and brain natriuretic peptide (BNP). All-cause mortality was analyzed by PE, RAA and other echocardiographic parameters for positive (PPV) and negative predictive value (NPV) to detect if the current guideline recommended cut-offs can precisely stratify risk in this setting. A survival analysis was performed to evaluate risk stratification (RS) provided by several different cut-offs. Results A total of 51 PH pts (mean age 54±46 years, 33.3% male, baseline BNP of 342.4±439.9pg/mL, mean 6MWT distance of 360.3±109.2 meters and baseline pulmonary artery systolic pressure of 78±26mmHg), of which 64.7% had Group I PH (GI) and 35.3% presented chronic thromboembolic pulmonary hypertension. There were no significant differences between these two groups, however pts in GI were significantly younger (p=0.001), achieved a lower 6MWT distance (p=0.038) and had worse values of right ventricular strain (p=0.040). 27 pts (52.9%) died during a mean follow-up of 52 months, with no differences between groups (p=0.756). The presence of a PE had a low NPV and PPV for the primary endpoint (45.0% and 45.5%, respectively), as well as the guideline recommended cut-offs for RAA (18cm2: NPV- 50.0% and PPV– 55.2%; 26cm2: NPV- 51.3% and PPV– 66.7%). A Pulsed Doppler Tei index (TIp) cut-off of 0.40 had a higher NPV (70.8%) and PPV (74.1%). By Kaplan-Meieran alysis, neither the presence of PE (log rank p=0.508) nor the recommended RAA cut-offs provided accurate risk discrimination (log rank p&amp;gt;0.05 for all). Pts below a TIp cut-off of 0.40 presented a significantly lower survival during follow-up (log rank p=0.002) Conclusion The currently recommended echocardiographic prognostic markers cannot precisely discriminate risk in PH pts. Markers of Right Ventricular Dysfunction may improve RS in this population. Funding Acknowledgement Type of funding sources: None.

Prospective Study of Cardiac Events during Proteasome Inhibitor Therapy for Relapsed Multiple Myeloma

Introduction: Cardiovascular (CV) toxicity has been reported with use of proteasome inhibitors (PI) for multiple myeloma (MM). However, detailed descriptions of the frequency and severity of cardiovascular adverse events (CVAE) and risk factors associated with CVAEs are lacking. We conducted a prospective, observational, multi-institutional study to define CV risk factors and outcomes in MM patients receiving bortezomib or carfilzomib.Methods: Patients with relapsed MM who were starting therapy with a regimen containing either carfilzomib (Car)- or bortezomib (Bor)- underwent a detailed baseline CV assessment including: assessment of traditional CV risk factors (CVRF; family history, hypertension (HTN), hyperlipidemia, diabetes and tobacco use), cardiac biomarkers [troponin I and T, brain natriuretic peptide (BNP) and N-terminal proBNP (NTproBNP)], electrocardiogram (ECG), transthoracic echocardiogram, and evaluation by a cardiologist. Patients with light chain amyloidosis were excluded.CV assessments were performed at baseline and at the start of each chemotherapy cycle (i.e. every 3 or 4 weeks). Cardiac biomarkers were tested twice per cycle for up to 6 cycles. Patients were followed for development of CVAEs for a period of 18 months, defined according to the CTCAE v4.03: heart failure (HF), arrhythmia requiring treatment, acute coronary syndrome (ACS), grade III or IV HTN, angina, venous thromboembolic event (VTE) and pulmonary HTN (PH). All CVAEs were confirmed by a cardiologist.Results: 97 patients were enrolled, with 65 receiving Car- and 32 Bor-therapy with a median follow-up of 14 months. Patients received a median of 2 prior lines of therapy in the Car group, and 1 prior line in the Bor group. There was no difference in baseline natriuretic peptide levels between cohorts (P=0.26). In total, 61 cardiac AEs occurred, with 54% being ≥ grade 3 (Table 1). Of evaluable patients, 50% (n=32) receiving Car and 15% (n=4) receiving Bor experienced at least one CVAE (P=.002). The median time to CVAE from start of treatment was 33 days, with the majority (86%) occurring within the first 3 months of treatment (Figure). Seventeen patients with CVAE (47%) experienced ≥2 CVAEs.In patients receiving Car-therapy, a baseline BNP >100 pg/ml or NTproBNP >125 pg/ml was associated with an increased risk of CVAE (OR 11.7, 95% CI 3.3-41.5; P <.001). In patients with normal baseline natriuretic peptide levels, an increase during cycle 1 was associated with a higher risk of CVAE (OR of 35.1, 95% CI 4.3-289.5, P <.001).In multivariate analysis (Table 2), Car-therapy was associated with a higher risk of CVAE (HR 5.4, 95% CI 1.6 to 18.4; P <.001) as compared to Bor-therapy. Elevated baseline natriuretic peptide levels were associated with higher risk of CVAE (HR 4.4, 95% CI 2.2 to 8.9; P <.001), and patients with ≤ 1 baseline CVRF had a lower risk of CVAE (HR 0.5, 95% CI 0.3 to 0.9, P=0.02). Other assessments evaluated and not found to be predictive of CVAEs included baseline troponins, ECG, left ventricular ejection fraction, intravenous fluid volume, chemotherapy duration, corticosteroid use and higher Car dose levels.The majority (68%) of patients with CVAEs resumed PI-based therapy after CVAE without chemotherapy modification; another 30% who experienced a CVAE were able to resume PI-therapy with chemotherapy modifications. Only 2% required discontinuation of therapy due to CVAE. One grade 5 toxicity occurred during Car treatment from ACS leading to sudden cardiac death.Summary and Conclusions: This is the first prospective study designed to systematically evaluate cardiac events in patients receiving carfilzomib or bortezomib. CVAEs were more common with Car than with Bor but usually did not require discontinuation of therapy with careful management. Additionally, prospective monitoring with natriuretic peptides and detailed cardiac history to determine risk factors are useful in identifying patients at high risk of CVAEs during treatment with PIs. [Display omitted] DisclosuresWeiss:Alnylam: Honoraria; Prothena: Research Funding; Janssen: Honoraria; Prothena: Honoraria; Janssen: Research Funding. Cohen:Bristol Meyers Squibb: Consultancy, Research Funding; GlaxoSmithKline: Consultancy; Celgene: Consultancy; Janssen: Consultancy. Jagasia:Janssen: Consultancy, Research Funding; Mallinckrodt: Consultancy; Therakos: Consultancy, Research Funding. Moslehi:Pharmacyclics: Consultancy; Daiichi Sankyo: Consultancy; Novartis: Consultancy; Pfizer: Consultancy; Bristol-Myers Squibb: Consultancy; Takeda: Consultancy; Ariad: Consultancy; Acceleron: Consultancy; Incyte: Consultancy; Vertex: Consultancy; Regeneron: Consultancy; StemCentRx: Consultancy; Verastem: Consultancy; Heat Biologics: Consultancy; Rgenix: Consultancy. Savona:Sunesis: Research Funding; Gilead: Membership on an entity's Board of Directors or advisory committees; Incyte Corporation: Consultancy, Research Funding; Amgen: Membership on an entity's Board of Directors or advisory committees; Takeda: Research Funding; Astex: Membership on an entity's Board of Directors or advisory committees, Research Funding; Karyopharm: Consultancy, Equity Ownership; Celgene: Membership on an entity's Board of Directors or advisory committees; TG Therapeutics: Membership on an entity's Board of Directors or advisory committees, Research Funding. Vogl:Karyopharm: Consultancy; Takeda: Consultancy, Research Funding; Amgen: Consultancy; Celgene: Consultancy; Teva: Consultancy; GSK: Research Funding; Calithera: Research Funding; Constellation: Research Funding.

794-P: Predictors of Hemoglobin (Hb) and Its Changes Focusing on Anemia and Polycythemia after Administration of the SGLT2 Inhibitor Tofogliflozin

SGLT2 inhibitors (SGLT2is) increase hematocrit (Ht) and Hb, which may contribute to correcting anemia but also might cause secondary polycythemia. We investigated predictors of Hb after short- and long-term therapy with tofogliflozin (TOFO), a SGLT2i, and explored its impact on Hb in relation to anemia and polycythemia in type 2 diabetes mellitus (T2DM). Analyzed were 774 T2DM patients (66% male) who received TOFO for 52 weeks in two phase 3 studies. Mean baseline characteristics were age 59 y, HbA1c 8%, BMI 26 kg/m2, hemoglobin 15 g/dL and eGFR 84 mL/min/1.73m2. Participants were divided into the Anemia group (baseline Hb &amp;lt;13 g/dL in men and &amp;lt;12 g/dL in women, mean baseline Hb 11.8 g/dL) and Polycythemia group (&amp;gt;16.5 g/dL in men and &amp;gt;16 g/dL in women, mean baseline Hb 17.2 g/dL). Paired t-tests analyzed differences from baseline to weeks 4 and 52. Generalized linear model explored predictors of Hb at weeks 4 and 52. Correlation analysis was performed by Spearman’s product-moment correlation coefficients. Hb was significantly increased at week 4 [mean, +0.14g/dL*; *p&amp;lt;0.05 vs. baseline] and week 52 (+0.34g/dL*). Higher baseline brain natriuretic peptide and lower Ht and triglycerides (TG) were independently correlated with greater increases in Hb at week 4. Lower baseline Hb and TG were significantly correlated with greater increases in Hb at week 52. Higher baseline TG levels and proportion of fatty liver as a comorbidity were observed with higher baseline Hb values. Hb had significantly changed at week 52 in Anemia (+0.94*) and Polythycemia groups (-0.29*). Change in Hb was significantly correlated with change in TG at week 52 (Rho=0.42, p&amp;lt;0.05) in Polycythemia but not Anemia. Increased Hb after short-term TOFO therapy may be due to hemoconcentration while Hb may be corrected according to baseline Hb levels after long-term TOFO therapy. Lower TG in relation to improved fatty liver may be related to correction of higher Hb levels. Disclosure Y. Matsubayashi: None. A. Yoshida: Employee; Self; Kowa Company, Ltd. H. Suganami: Employee; Self; Kowa Company, Ltd. K. Kaku: Advisory Panel; Self; Novo Nordisk Pharma Ltd., Consultant; Self; Sanwa Kagaku Kenkyusho, Research Support; Self; Taisho Pharmaceutical Co., Ltd., Speaker’s Bureau; Self; Astellas Pharma Inc., AstraZeneca, Eli Lilly Japan K. K., Mitsubishi Tanabe Pharma Corporation, Nippon Boehringer Ingelheim Co. Ltd., Sumitomo Dainippon Pharma Co., Ltd., Takeda Pharmaceutical Co. H. Sone: Research Support; Self; Astellas Pharma Inc., Eisai Co., Ltd., Kyowa Kirin Co., Ltd., Novo Nordisk, Ono Pharmaceutical Co., Ltd., Taisho Pharmaceutical Co., Ltd., Takeda Pharmaceutical Co.

Biomarkers Associated with Mortality in Aortic Stenosis: A Systematic Review and Meta-Analysis.

The optimal timing of aortic valve replacement (AVR) remains controversial. Several biomarkers reflect the underlying pathophysiological processes in aortic stenosis (AS) and may be of use as mortality predictors. The aim of this systematic review and meta-analysis is to evaluate the blood biomarkers utilised in AS and assess whether they associate with mortality. PubMed and Embase were searched for studies reporting baseline biomarker level and mortality outcomes in patients with AS. A total of 83 studies met the inclusion criteria and were systematically reviewed. Of these, 21 reporting brain natriuretic peptide (BNP), N-terminal pro B-type natriuretic peptide (NT-proBNP), Troponin and Galectin-3 were meta-analysed. Pooled analysis demonstrated that all-cause mortality was significantly associated with elevated baseline levels of BNP (HR 2.59; 95% CI 1.95–3.44; p < 0.00001), NT-proBNP (HR 1.73; 95% CI 1.45–2.06; p = 0.00001), Troponin (HR 1.65; 95% CI 1.31–2.07; p < 0.0001) and Galectin-3 (HR 1.82; 95% CI 1.27–2.61; p < 0.001) compared to lower baseline biomarker levels. Elevated levels of baseline BNP, NT-proBNP, Troponin and Galectin-3 were associated with increased all-cause mortality in a population of patients with AS. Therefore, a change in biomarker level could be considered to refine optimal timing of intervention. The results of this meta-analysis highlight the importance of biomarkers in risk stratification of AS, regardless of symptom status.

Right atrial strain by speckle-tracking echocardiography as a prognostic predictor in a pulmonary hypertension cohort

Abstract Funding Acknowledgements Type of funding sources: None. Background Right atrial (RA) strain is as a promising technique for assessment of RA function and several studies have suggested it is a powerful prognostic marker in pulmonary hypertension (PH) patients (pts). Our aim was to assess the prognostic power of RA strain in Pulmonary Arterial Hypertension (PAH) and Chronic Thromboembolic Pulmonary Hypertension (CTEPH) pts. Methods Pts with PH were prospectively studied and several clinical/demographic/echocardiographic were retrieved as well as data from six-minute walk test (6MWT) and brain natriuretic peptide (BNP). Correlation between RA strain and other variables was tested with Pearson"s correlation analysis. Regression and survival analysis were performed to assess the combined endpoint of all-cause mortality or hospitalization in the first follow-up year (MH1). Results A total of 51 PH pts (mean age 54 ± 46 years, 33.3% male, baseline BNP of 342.4 ± 439.9pg/mL and baseline pulmonary artery systolic pressure – PASP - of 78 ± 26mmHg), of which 64.7% had PAH and 35.3% presented CTEPH. 19 ots (37.3%) met the primary endpoint. The mean RA strain was -21.9 ± -4.9%, with no significant difference between groups (-23.4% vs -17.8%, p = 0.150), however male pts had a significantly lower RA strain (-15.9% vs -25.1%, p = 0.014). There was a statistically significant (p &amp;lt; 0.05) correlation between RA strain and age (r = -0.287), indexed RA area (r = -0.539), index RA volume (r = -0.522) and right ventricular strain (r = -0.453). There was no correlation between RA strain and BNP value (p = 0.150), 6MWT distance (p = 0.145) or PASP (p = 0.072). RA strain was a predictor of MH1 (OR = 0.94, 95% CI: 0.894-0.998, p = 0.048). Pts who met the primary endpoint had a significantly worse RA strain (-17.0 vs -24.6%, p = 0.032). Those with a RA strain worse than -19% presented a significantly lower survival free of events during the first follow-up year (log rank p = 0.022). Conclusion RA strain is a powerful predictor of adverse events in a PH population and should be systematically assessed in order to improve risk stratification. Abstract Figure.

1133-P: Association of Higher Baseline BNP Levels with a Greater Reduction in Plasma Volume and Increase in Beta-Hydroxybutyrate via the SGLT2 Inhibitor Tofogliflozin in Type 2 Diabetes

Reduced plasma volume (PV) to decrease ventricular filling pressure and increased beta-hydroxybutyrate (BHB) as a substitute for the energy source by SGLT2 inhibitors (SGLT2is) might contribute to preserving the heart in type 2 diabetes mellitus (T2DM). However, the impact of SGLT2is on PV and BHB is little known according to cardiac workload. We investigated the effect of long-term treatment with the SGLT2i, tofogliflozin, on PV and BHB according to baseline brain natriuretic peptide (BNP) levels in T2DM. Analyzed were 774 T2DM patients who received tofogliflozin for 52 weeks as mono- and add-on-therapy in two phase-3 studies. Percent change in estimated PV (%ΔePV) was calculated by the Strauss formula: {100*(pre Hb/post Hb)*[(100 - post Ht)/(100 - pre Ht)] - 100}. We divided patients into two groups (Quartiles 1-3[Q1-3] and Quartile 4[Q4]) according to baseline BNP. Differences in characteristics were analyzed using unpaired t-test, wilcoxon rank sum test or Fisher’s exact test. Differences in changes between groups were analyzed using an analysis of covariance model. Multivariate analysis evaluated the association of baseline BNP with changed variables. Baseline characteristics were: male (71 vs. 52% *, * p&amp;lt;0.05, Q1-3 vs. Q4), age (mean: 57 vs. 64 y *), HbA1c (8.1 vs. 8.0%), BMI (26 vs. 25 kg/m2 *), BNP (median: 9 vs. 27 pg/mL *) and BHB (45 vs. 54 µmol/L). Reduction in Ln-transformed BNP (ln-BNP) was greater in Q4 (least square mean: -0.5 ln[pg/mL]) than in Q1-3 (-0.1) as was %ΔePV (Q4 [-6 %] vs. Q1-3 [-4]). Increase in Ln-transformed BHB (ln-BHB) was larger n Q4 (+0.7 ln[µmol/L]) than in Q1-3 (+0.5). Changes in HbA1c, body weight and blood pressure were similar. Q4 was independently correlated with the greater reduction in %ΔePV and increase in ln-BHB. Results suggested that reduced PV and increased BHB might be greater in T2DM patients with higher baseline BNP levels after long-term tofogliflozin therapy. Disclosure A. Yoshida: Employee; Self; Kowa Company, Ltd. Y. Matsubayashi: None. T. Nojima: Employee; Self; Kowa Company, Ltd. H. Suganami: Employee; Self; Kowa Company, Ltd. M. Oe: Employee; Self; Kowa Company, Ltd. K. Fujihara: None. S. Tanaka: None. K. Kaku: Advisory Panel; Self; Nippon Boehringer Ingelheim Co. Ltd., Novo Nordisk Inc. Consultant; Self; Sanwa Kagaku Kenkyusho. Research Support; Self; Taisho Pharmaceutical Co., Ltd. Speaker’s Bureau; Self; Astellas Pharma Inc., AstraZeneca, Daiichi Sankyo, Eli Lilly Japan K.K., Kowa Company, Ltd., Merck Sharp &amp; Dohme Corp., Mitsubishi Tanabe Pharma Corporation, Ono Pharmaceutical Co., Ltd., Takeda Pharmaceutical Company Limited. H. Sone: Research Support; Self; Kyowa Hakko Kirin Co., Ltd., Novartis AG, Ono Pharmaceutical Co., Ltd., Taisho Pharmaceutical Co., Ltd., Takeda Pharmaceutical Co.

P1030Elevated baseline brain natriuretic peptide level was associated with poor outcome after multiple catheter ablation for paroxysmal atrial fibrillation

Abstract Background Serum Brain Natriuretic Peptide (BNP) level is associated with various cardiovascular events. Because elevated BNP level reflects increased left ventricular end-diastolic pressure and LA pressure promoting left atrial (LA) remodeling, BNP level might be associated with the extent of arrhythmogenic substrate in patients with atrial fibrillation (AF). We hypothesized that elevated BNP level has impact on outcome after catheter ablation (CA) for AF. Purpose We investigated the impact of baseline BNP level on outcome after multiple CA for paroxysmal atrial fibrillation (PAF), and assessed the association between baseline BNP level and extent of LA remodeling. Methods This was a retrospective, single-center observational study. A total of 287 patients who underwent CA for PAF in our institute from March 2012 to March 2014. All patients had dataset of baseline BNP level and LA volume measured by multi-detector computed tomography (MDCT) in sinus rhythm. First we performed receiver operating characteristic (ROC) analysis for recurrence after multiple CA and obtained the best cut-off value of BNP. Patients were divided into Low BNP and High BNP group based on BNP cut-off value, and AF-free survival was analyzed with log-rank test. To assess the impact of BNP level on recurrence, multivariate Cox regression model were performed. Finally, we assessed the extent of baseline LA remodeling in low BNP and high BNP group. Results During follow-up period, AF recurred in 65/287 patients (26.2%) after multiple CA procedure (follow up 3.4 [2.2, 4.0] years, total number of sessions: 1.39±0.63). Patients with recurrence had greater baseline BNP than those without recurrence (99.8 pg/mL [30.0, 128] vs. 60.7 pg/mL [17.3, 80.8], recurrence vs. no-recurrence, P&lt;0.05). In ROC analysis, baseline BNP had mild accuracy for the prediction of recurrence (AUC: 0.63, P=0.002, best cut-off value: 57.3 pg/mL). We divided patients into High BNP group (BNP≥57.3, N=106) and Low BNP group (BNP&lt;57.3, N=181). AF-free survival was higher in Low BNP than in High BNP (Figure 1) (83.4% vs. 67.0%, Low vs. High, P&lt;0.001). After adjustment with age, gender, hypertension, heart failure, body mass index, LA diameter and LV ejection fraction, High BNP (BNP≥57.3) was associated with recurrence (Hazard ratio: 2.31, 95% CI 1.42–3.75, P&lt;0.001). In baseline parameters of LA remodeling measured with MDCT, Low BNP group had higher LA emptying fraction (41.7±9.5 vs. 32.0±8.5%, Low vs. High, P&lt;0.001) and lower indexed maximum LA volume (48.5±12.0 vs. 61.3±16.7 mL/m2, P&lt;0.001) (Figure 2). Conclusion Baseline serum BNP level was associated with recurrence after multiple procedures for PAF. The baseline extent of LA remodeling was greater in High BNP than in Low BNP. Elevated BNP level might reflect the severe LA remodeling causing ablation-refractory AF even after multiple CA. The preoperative assessment of BNP might be helpful for prediction of multiple CA outcome.

A high BNP level predicts an improvement in exercise tolerance after a successful catheter ablation of persistent atrial fibrillation.

Restoration of sinus rhythm (SR) by catheter ablation (CA) of atrial fibrillation (AF) improves exercise tolerance. However, it is still unclear what characteristics of patients are contributing to an improvement in exercise tolerance after CA of AF without heart failure. This study consisted of 51 consecutive patients with persistent or long-standing persistent AF without heart failure who were restored to SR for over 6 months by a successful CA. Exercise tolerance was evaluated by cardiopulmonary exercise testing before and 3 and 6 months after CA. The clinical characteristics contributing to an improvement in exercise tolerance was elucidated. The peak oxygen uptake (VO2 )% significantly increased from 101.4 ± 20.3% to 110.9 ± 19.9% 3 months after the CA (P < .001). The improvement rate in the peak VO2 % exhibited a positive correlation to the baseline brain natriuretic peptide (BNP; ρ = 0.39, P < .01), but not to the age, AF duration, left ventricular ejection fraction, or left atrial size. The linear regression analysis revealed that the baseline BNP was an independent predictor of an improvement in the peak VO2 % (coefficients = 0.32; 95% confidence interval = 0.08, 0.54; P = .01). The peak VO2 % improved significantly in the patients whose baseline BNP level was greater than 100 pg/mL, compared to the others (P < .01). These favorable findings were also observed 6 months after the CA. Elimination of persistent AF by CA was associated with an improvement in exercise tolerance. This was particularly true in patients with high BNP values at baseline.

The utility of brain natriuretic peptides in septic shock as markers for mortality and cardiac dysfunction: A systematic review.

To conduct a systematic review evaluating the utility of brain natriuretic peptide (BNP) and N-terminal proBNP (NT-proBNP) as biomarkers in adult patients with septic shock. Pubmed/Medline databases were searched from inception to November 2018 using the search terms: (septic[Title/Abstract] AND shock[Title/Abstract]) AND bnp[Title/Abstract]) and (septic[Title/Abstract]) AND shock[Title/Abstract]) AND natriuretic[Title/Abstract]). No restriction was applied regarding date of publication. Comparative observational studies evaluating BNP and NT-proBNP in patients with septic shock aged ≥18years were eligible for inclusion. Bibliographies from the extracted articles were also reviewed to identify additional relevant publications. In total, 46 studies met all eligibility criteria and were included. A strong body of literature has demonstrated that in patients with septic shock, increased values of BNP and NT-proBNP are associated with increased mortality. An increase from baseline BNP values has also been associated with increased mortality, whereas decreases from baseline values are not related to worse outcome. Brain natriuretic peptides have also been associated with cardiac dysfunction in patients with sepsis. Moreover, BNP values have been found to be significantly elevated in septic shock, regardless of cardiac dysfunction, and have been used to distinguish between septic and cardiogenic shock. Furthermore, BNP and NT-proBNP are significantly increased in patients with septic shock, compared to patients with sepsis and severe sepsis. BNP and NT-proBNP appear to be reliable predictors of outcome in septic shock.

The effect of luseogliflozin and alpha-glucosidase inhibitor on heart failure with preserved ejection fraction in diabetic patients: rationale and design of the MUSCAT-HF randomised controlled trial

IntroductionType 2 diabetes mellitus (T2DM) is a strong risk factor for coronary artery disease and heart failure, particularly heart failure with preserved ejection fraction (HFpEF). The aim of the ongoing...