Baseline N-terminal Pro-brain Natriuretic Peptide Research Articles

Excess long-term risk of adverse outcomes in heart failure patients with high and low levels of NT-proBNP: A 7-year follow-up study (NorthStar Trial)

BackgroundThis study investigated excess risk in patients with heart failure with reduced left ventricular ejection fraction (HFrEF) with or without elevated levels of NT-proBNP (N-terminal pro-brain natriuretic peptide). MethodsPatients with HFrEF from the NorthStar cohort (n = 1120) were matched on age, sex, and presence of AF (atrial fibrillation/flutter) to five controls without HFrEF from The Danish National Patient Registries. Patients were compared with controls before and after stratification according to baseline NT-proBNP levels, with cutoffs defined as </≥ 600 pg/ml in patients with sinus rhythm and </≥ 900 pg/ml in patients with AF. The primary composite endpoint was a 7-year risk of cardiovascular death or HF admission. ResultsIn the HFrEF cohort, 704 patients had high NT-proBNP (median age, 73; mean left ventricular ejection fraction (LVEF), 33%). 416 patients had low NT-proBNP (median age, 65; LVEF, 30%). Patients from both groups were in NYHA class I-III. The primary endpoint occurred in 531 patients (75.4%) with HFrEF and elevated NT-proBNP, and 748 controls (21.3%) (risk difference, 54.2%; 95% confidence interval (CI) 50.7–57.6%). In comparison, it occurred in 199 patients (47.9%) with HFrEF and without elevated NT-proBNP, and 185 controls (8,9%) (risk difference, 38.9%; 95% CI 34.0–43.9%). Risk differences for all secondary endpoints were significant, except for overall mortality in the low NT-proBNP group (risk difference, 3.8%; 95% CI, −0.4–8.0%). ConclusionThis study identified a significant excess risk in patients with HFrEF across various endpoints, which persisted after stratification into high and low levels of NT-proBNP.

Dynamic LVEF Decline and Serum NT-proBNP and Uric Acid Levels before Heart Transplantation are Independent Predictors of Adverse Outcomes in Young Adult Patients with Dilated Cardiomyopathy.

The present study investigated the predictors of adverse outcomes in young adult patients with dilated cardiomyopathy (DCM) who underwent heart transplantation (HTx). Twenty-four young adult patients (aged 18-45 years) with DCM who underwent HTx in our hospital from January 2012 to December 2022 were included in this retrospective analysis. Pre- and post-HTx data were collected for echocardiography, N-terminal pro-brain natriuretic peptide (NT-proBNP), and uric acid (UA). Data collected at the time of DCM diagnosis were designated as baseline data. Post-HTx assessments were conducted at 1 week and 3, 6, 12, and 36 months post-HTx. The primary endpoint was defined as any adverse event, including left ventricular ejection fraction (LVEF) 50% (n = 3), 50% increase in right or left ventricular diameter (n = 12), or death (n = 2). Patients were categorized into a non-adverse-event group (n = 12) or an adverse-event group (n = 12). Baseline NT-proBNP (p = 0.014) and UA (p = 0.012) were significantly higher in the adverse-event group than in the non-adverse-event group. Baseline NT-proBNP 7390 pg/mL (relative risk (RR) = 7.412, p = 0.046), UA 542 µmol/L (RR = 8.838, 95% confidence interval (95% CI) = 1.541-50.694, p = 0.014), and sustained reduction in LVEF ( 3%) over a 2-year pharmacological treatment prior to HTx (RR = 3.252, p = 0.046) were significantly associated with an increased risk of adverse events post-HTx. In young adult DCM patients post-HTx, heightened baseline levels of NT-proBNP and UA levels and a sustained reduction in LVEF over time prior to undergoing an HTx are significantly associated with an increased risk of adverse events post-HTx. Future studies are needed to observe whether individualized monitoring strategies could reduce the incidence of adverse events following HTx in these patients.

Comparative analysis of different risk prediction tools after mitral Transcatheter edge-to-edge repair

BackgroundTranscatheter edge-to-edge repair (TEER) has become an established treatment for primary and secondary mitral regurgitation (PMR and SMR). The objective of this study was to compare the accuracy of different risk scores for predicting 1-year mortality and the composite endpoint of 1-year mortality and/or heart failure (HF) hospitalization after TEER. MethodsWe analyzed data from 206 patients treated for MR at a tertiary European center between 2011 and 2023 and compared the accuracy of different mitral and surgical risk scores: EuroSCORE II, GRASP, MITRALITY, MitraScore, TAPSE/PASP-MitraScore, and STS for predicting 1-year mortality and the composite of 1-year mortality and/or HF hospitalization in PMR and SMR. A subanalysis of SMR-only patients with the addition of COAPT Risk Score and baseline N-Terminal pro-Brain Natriuretic Peptide (NT-proBNP) list was also performed. ResultsMITRALITY had the best discriminative ability for 1-year mortality and the composite endpoint of 1-year mortality and/or HF hospitalization, with an area under the curve (AUC) of 0.74 and 0.74, respectively, in a composed group of PMR and SMR. In a SMR-only population, MITRALITY also presented the best AUC for 1-year mortality and the composite endpoint of 1-year mortality and/or HF hospitalization, with values of 0.72 and 0.72, respectively. ConclusionMITRALITY was the best mitral TEER risk model for both 1-year mortality and the composite endpoint of 1-year mortality and/or HF hospitalization in a population of PMR and SMR patients, as well as in SMR patients only. Surgical risk scores, MitraScore, TAPSE/PASP-MitraScore and NT-proBNP alone showed poor predictive values.

Safety and Tolerability of Cael-101, an Anti-Amyloid Monoclonal Antibody, Combined with Anti-Plasma Cell Dyscrasia Therapy in Patients with Light-Chain Amyloidosis: 24-Month Results of a Phase 2 Study

Background: Light-chain (AL) amyloidosis is a rare, systemic disease caused by plasma cell dyscrasia (PCD). Immunoglobulin light chains misfold and deposit in organs as insoluble amyloid fibrils. The extent of cardiomyopathy due to amyloid deposition determines patient survival. Current therapies target PCD to halt amyloid formation but do not treat existing amyloid deposits in organs. CAEL-101 is a novel, investigational, potentially first-in-class therapy to remove amyloid fibrils from organs. Aims: To present safety, tolerability, and biomarker data after 110 weeks of treatment with CAEL-101, administered initially with cyclophosphamide-bortezomib-dexamethasone (CyBorD) ± daratumumab. Methods: Adult patients with AL amyloidosis (European Modification of Mayo Stage I-IIIa) and measurable hematologic disease were eligible for this ongoing, open-label, phase 2 study (NCT04304144). Other forms of amyloidosis and multiple myeloma were excluded. CAEL-101 ≤1000 mg/m 2 was administered with CyBorD therapy ± daratumumab as directed by the investigator. In addition to safety assessments, cardiac response was assessed by change over time in N-terminal pro-brain natriuretic peptide (NT-proBNP). Results: Patients (N = 25; mean age 65 years; 72% male) with Mayo Stage I (n = 2; 8%), II (n = 19; 76%), and IIIa (n = 4; 16%) AL amyloidosis were enrolled to be treated with CAEL-101. All 25 patients experienced treatment-emergent adverse events (TEAEs); 6 (24%) experienced TEAEs possibly related to CAEL-101, 17 (68%) experienced ≥1 adverse event of ≥Grade 3 severity, and 15 (60%) experienced ≥1 serious adverse event. There were a total of 447 TEAEs reported of which only 67 (15%) were Grade ≥3. As of the cutoff date of 22 May 2023, 12 (48%) patients had discontinued the study due death (n = 3), patient withdrawal (n = 3), physician decision (n = 2), heart transplant (n = 2), heart and kidney transplant (n = 1), and adverse event (n = 1). The most common adverse events reported by ≥5 (20%) patients were fatigue (n = 12), anemia (n = 10), nausea (n = 10), constipation(n = 9), diarrhea (n = 9), cough (n = 8), dizziness (n = 8), insomnia (n = 7), peripheral neuropathy (n = 7), dyspnea (n = 6), hypokalemia (n = 6), rash (n = 6), and headache (n = 5), peripheral edema (n = 5), vomiting (n = 5). There were 22 cardiac-evaluable patients (baseline NT-proBNP &amp;gt;332 ng/L) enrolled in this trial. After 110 weeks of CAEL-101 treatment, 6 (27%) patients were cardiac responders (&amp;gt;30% NT-proBNP decrease and more than 300 ng/L decrease, if baseline NT-proBNP ≥650 ng/L), 7 (32%) patients were stable (neither response nor progression), and 2 (9%) patients showed cardiac disease progression (&amp;gt;30% increase and ≥300 ng/L increase from baseline in the absence of eGFR decline of ≥25%); data for 7 (32%) patients were missing. Cardiac response over time to 110 weeks of CAEL-101 treatment is shown in Figure). Conclusions: Patients in this analysis have been treated for ≥24 months and CAEL-101 was generally well tolerated without evidence of organ toxicity. Long-term safety evaluation of CAEL-101 continues in this study. Most TEAEs (85%) were mild to moderate. Two phase 3 trials (NCT04504825 and NCT04512235) are in progress to study the efficacy and safety of CAEL-101 in cardiac AL amyloidosis European Modification Mayo Stages IIIa and IIIb.

Abstract 14347: Albuminuria, N-Terminal Pro-Brain Natriuretic Peptide and Incident Congestive Heart Failure in High-Risk Adults With Hypertension: A Post Hoc Analysis of the Systolic Blood Pressure Intervention Trial

Introduction: Abnormal levels of urinary albumin concentration (UAC) and N-terminal pro-Brain Natriuretic Peptide (NT-proBNP) have each been independently associated with an increased risk of congestive heart failure (CHF). It remains unknown whether the concomitant presence of abnormal UAC and NT-proBNP increases an individual’s risk for future CHF beyond that contributed by each biomarker. Objective: To examine the joint association between abnormal UAC and NT-ProBNP with incident CHF in participants from the SPRINT (Systolic Blood Pressure Intervention Trial) study. Methods: This analysis included 8,176 participants from SPRINT with available data on baseline UAC and NT-proBNP. UAC was measured by urine albumin-creatinine ratio (UACR). Albuminuria was defined as UACR ≥30 mg/g. Abnormal NT-proBNP was defined as levels ≥125 pg/ml. Cox proportional hazard models were used to examine the association of UAC and NT-proBNP, as well as albuminuria and abnormal NT-proBNP, with incident CHF. Results: Over a median follow-up of 3.2 years, 179 incident cases of CHF were observed. In adjusted models, the risk of incident CHF (HR 95% CI) associated with each 1 (one) unit standard deviation increase in the levels of UAC and NT-proBNP was 1.10 (1.04-1.16; p &lt;0.001) and 1.13 (1.10-1.16; p &lt;0.0001), respectively. A statistically significant multiplicative interaction between UAC*NT-proBNP was observed in the fully adjusted model (p &lt;0.0001). The risk associated with the presence of abnormal UAC +/- abnormal NT-proBNP in the SPRINT cohort is depicted in the figure. Conclusions: Among SPRINT participants, we found a significant multiplicative interaction between UAC and NT-proBNP as predictors of incident CHF. Also, the risk of future CHF was over six times higher in individuals with abnormal UAC and NT-proBNP, compared with those with normal levels of both biomarkers. More studies are needed to further explore this interaction and the implications on CHF prevention.

Influence of left ventricular ejection fraction on the reduction in N-terminal pro-brain natriuretic peptide by canagliflozin in patients with heart failure and type 2 diabetes: A sub analysis of the CANDLE trial

AimTo investigate the effect of left ventricular ejection fraction (LVEF) on the behavior of N-terminal pro-brain natriuretic peptide (NT-proBNP) levels in patients with heart failure and type 2 diabetes mellitus with the use of canagliflozin compared to glimepiride. MethodsPatients (n = 233) from the CANDLE trial were randomly assigned to either the add-on canagliflozin (n = 113) or glimepiride treatment groups (n = 120). The patients were followed-up for 24 weeks. The NT-proBNP levels were measured at baseline and after 24 weeks. The LVEF was determined at baseline. ResultsThere was a significant relationship between the baseline NT-proBNP level (X1) and the change in NT-proBNP levels from baseline to 24 weeks (Y) in the canagliflozin group (Y = −0.533 × X1 + 178; r = −0.860, p < 0.001). However, this relationship was not observed in the glimepiride group (p = 0.428). The baseline LVEF (X2) correlated with Y with a marginal significance in the canagliflozin group (Y = 7.72 × X2–549; r = 0.192, p = 0.054), but no relationship was observed in the glimepiride group. In the canagliflozin group, bivariate regression analysis showed a significant correlation between Y, X1, and X2; Y = −0.567 × X1–6.04 × X2 + 542 (R = 0.871, p < 0.001). The partial regression coefficients of X1 (p < 0.001) and X2 (p = 0.006) significantly explained the variance in Y. The correlation coefficient for X2 was negative. There was a significant relationship between the logarithmically transformed NT-proBNP [ln(NT-proBNP)] at baseline (X1′) and the change in ln(NT-proBNP) values from baseline to 24 weeks (Y′), a surrogate of the rate of change in NT-proBNP levels, in the canagliflozin group (Y′ = −0.18 × X1′ + 0.93; r = 0.450, p = 0.001). ConclusionsThe baseline NT-proBNP level significantly affected the extent and the rate of its decrease by canagliflozin. The reduction in NT-proBNP levels by canagliflozin was prominent in patients with a higher LVEF at baseline. However, its confounding effect of LVEF on canagliflozin treatment was not recognized without adjusting for the NT-proBNP level at baseline.

1-Year Results from a Phase 2 Study to Determine Safety and Tolerability of Treating Patients with Light-Chain (AL) Amyloidosis with Cael-101, an Anti-Amyloid Monoclonal Antibody, Combined with Anti-Plasma Cell Dyscrasia

Background: Light-chain (AL) amyloidosis is a rare, systemic disease caused by plasma cell dyscrasia (PCD). Excess immunoglobulin light chains misfold and form insoluble amyloid fibrils that deposit in organs, primarily the heart. Survival depends largely on the extent of heart involvement. Current therapies target PCD to halt fibril formation but do not treat existing fibril deposited in organs. CAEL-101 is a novel, investigational, potentially first-in-class therapy designed to remove amyloid fibrils from organs. Safety, tolerability, and biomarker data after all patients with AL amyloidosis enrolled in the trial received 1 year of treatment with CAEL-101, administered initially with cyclophosphamide-bortezomib-dexamethasone (CyBorD) ± daratumumab, are presented. Methods: Adult patients with AL amyloidosis (European Modification of Mayo Stage I-IIIa) and measurable hematologic disease were eligible for this ongoing, open-label, phase 2 study (NCT04304144). Other forms of amyloidosis and multiple myeloma were excluded. CAEL-101 ≤1000 mg/m2 is administered every other week with anti-PCD therapy as directed by the investigator. In addition to safety assessments, cardiac and renal response were assessed by change over time in N-terminal pro-brain natriuretic peptide (NT-proBNP) and proteinuria, respectively. Results: Patients (n = 25; mean age 65 years; 72% male) with Mayo Stage I (8%), II (76%), and IIIa (16%) AL amyloidosis were treated with CAEL-101 for 1 year at this analysis. Patients presented with cardiac involvement (n = 22), renal involvement (n = 9, reported from one site), and prior anti-PCD therapy (n = 20). All 25 patients experienced treatment-emergent adverse events (TEAEs), and 6 (24%) experienced at least possibly treatment-related TEAEs. Five patients discontinued for non-treatment-related reasons (Table). Fifteen (60%) patients experienced TEAEs of Grade ≥3 severity and 13 (52%) experienced ≥1 serious adverse event (SAE). The most common TEAEs were nausea (n = 10), constipation or fatigue (n = 9 each), anemia, insomnia, or diarrhea (n = 8 each), and dizziness, cough, or rash (n = 7 each). After 1 year of CAEL-101 treatment of the 22 cardiac evaluable patients (baseline NT-proBNP ≥332 pg/mL), 10 (46%) patients experienced ≥30% NT-proBNP decrease from baseline, 4 (18%) were stable (±30% change from baseline), and 3 (14%) showed disease progression (≥30% NT-proBNP increase from baseline); data for 5 patients were missing. Of the 9 renal evaluable patients from a single site as reported by the investigator, 8 showed ≥30% decrease from baseline in proteinuria. Conclusions: The long-term safety evaluation of CAEL-101 continues in this study. All patients currently enrolled have been treated for at least 1 year. At this 1-year time point, CAEL-101 has been generally well tolerated without evidence of organ toxicity. Organ response persisted even after cessation of anti-PCD treatment. Most TEAEs were mild to moderate. A phase 3 program has commenced to elucidate the efficacy and safety of CAEL-101 in cardiac AL amyloidosis European Modification Mayo Stages IIIa and IIIb. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Abstract 9343: Predictive Value of Baseline Serum High-Sensitivity Troponin I and NT-proBNP for Cardiac Immunotoxicity Risk During Immune Checkpoint Inhibitor Therapy

Introduction: Immune checkpoint inhibitors (ICI) have revolutionized cancer treatment, but rarely and unpredictably cause fulminant myocarditis. It is unknown if circulating cardiac biomarkers can predict immunotoxicity in a real-world patient population. Aim: To evaluate the predictive value of baseline levels of high-sensitivity troponin-I (hs-TnI) and N-terminal pro-brain natriuretic peptide (NT-proBNP) for myocardial injury (hs-TnI&gt;50ng/L) or potential heart failure (NT-proBNP&gt;300pg/mL) risk during ICI therapy. Methods: An institutional multidisciplinary working group developed a monitoring protocol for immune-related adverse events due to ICI. Data recorded during clinical treatment plans over 12 months starting 5/1/2021 were analyzed. Results: 621 patients received ICI therapy, and 6 developed myocarditis requiring hospitalization. Of 317 patients initiated on ICI after the start of this protocol, baseline and at least one follow-up hs-TnI and NT-proBNP values were measured in 183 and 126 patients, respectively. In 110 patients hs-TnI was undetectable (&lt;5ng/L) at baseline. In 66% of these patients hs-TnI remained undetectable on follow-up. Of 88 patients with baseline NT-proBNP below the diagnosis limit for heart failure (&lt;300 pg/mL), 75% had values below this limit on follow-up. The baseline value of the biomarkers was used as a predictor of increase in biomarkers during follow-up. Area under receiver operator curve for predicting an increase from baseline during ICI treatment was 0.67 for hs-TnI, 0.87 for NT-proBNP, and 0.86 combined (Figure). Conclusions: This single-center, prospectively protocolled, retrospectively-analyzed study indicates that hs-TnI and NT-proBNP values obtained at baseline and at least at one immunotherapy cycle can be used to categorize patients at risk or not for potential immunotoxicity during ICI treatment, thus may offer a helpful strategy in the monitoring and prevention of fulminant myocarditis.

Predictors for NYHA recovery and 1-year mortality after mitral TEER

Abstract Background Mitral regurgitation (MR) is the second-most frequent valvular heart disease in Europe and frequently aggravates heart failure (HF) symptoms. Mitral transcatheter-edge-to-edge repair (TEER) can be considered in eligible patients, for both primary (in inoperable cases) or secondary severe MR. However, intervention is not advised in severe comorbid patients in whom it is not expected to prolong survival for over 1 year. Purpose Evaluate characteristics associated with HF New York Heart Association (NYHA) class recovery, and one-year all-cause mortality after mitral TEER for severe MR. Methods All mitral TEER procedures for primary and secondary MR conducted in a single-centre between 2014 and 2020 were retrospectively analyzed. The primary endpoint was defined as a reduction of at least one NYHA class in the first month after intervention, and a secondary endpoint considered a recovery of at least two NYHA classes. Survival status 12 months after mitral TEER was also consulted. Clinical, echocardiographic and blood-analysis data were explored as characteristics associated with the endpoints defined, using Pearson's Chi-squared test, Wilcoxon rank sum test and Fisher's exact test, as appropriate. A p&amp;lt;0.05 was considered statistically significant. Results From 103 mitral TEER procedures, 86 (83%) had full information about pre- and post-intervention NYHA class, as well as survival status at 12 months. There was a higher proportion of primary MR among NYHA non-responders (47% versus 25%, p=0.034), but no differences for secondary MR. Higher surgical risk patients (EuroSCORE II) tended to have exhibit more NYHA recovery, though not reaching statistical significance (p=0.068). Both a more advanced NYHA class at baseline and lower N-terminal pro-brain natriuretic peptide (NTproBNP) levels were linked to a higher symptomatic recovery (2048 versus 5676pg/ml, p&amp;lt;0.001). Also, persisting MR after TEER of at least grade 3/4 was more frequent in non-NYHA responders. Regarding NYHA improvement of at least two classes, it was observed in 13% patients, and these also had a more advanced NYHA class at baseline and lower NTproBNP basal levels, and exhibited a lower estimated systolic pulmonary artery pressure and inferior vena cava (IVC) diameter. Finally, 10 (11.6%) of mitral TEER patients died in the first 12 months, and no statistically significant associations were found regarding pre-intervention characteristics and survival. Conclusions This study suggests that three-fifths of severe MR improve their NYHA class after TEER, but only one-fourth for primary MR. Earlier intervention – with lower NTproBNP levels, less severe pulmonary hypertension, and lower IVC diameters – is associated with more symptomatic HF improvement. All-cause mortality in the first year is still significant, exposing a need for better patient selection. However, these findings represent exploratory deductions of a relatively low number, single-centre, patients. Funding Acknowledgement Type of funding sources: None.

Prognostic value of N-terminal Pro-B-Type natriuretic peptide in patients with intermediate coronary lesions.

BackgroundThe optimal treatment strategy for patients with coronary intermediate lesions, defined as diameter stenosis of 50–70%, remains a great challenge for cardiologists. Identification of potential biomarkers predictive of major adverse cardiovascular events (MACEs) risk may assist in risk stratification and clinical decision.MethodsA total of 1,187 patients with intermediate coronary lesions and available N-terminal pro-brain natriuretic peptide (NT-proBNP) levels were enrolled in the current study. A baseline NT-proBNP level was obtained. The primary endpoint was defined as MACEs, the composite endpoint of all-cause death and non-fatal myocardial infarction. A multivariate Cox regression model was used to explore the association between NT-proBNP level and MACE risk.ResultsThe mean age of the study cohort was 59.2 years. A total of 68 patients experienced MACE during a median follow-up of 6.1 years. Restricted cubic spline analysis delineated a linear relationship between the baseline NT-proBNP level and MACE risk. Both univariate and multivariate analyses demonstrated that an increased NT-proBNP level was associated with an increased risk of MACE [adjusted hazard ratio (HR) per doubling: 1.412, 95% confidence interval (CI): 1.022–1.952, p = 0.0365]. This association remains consistent in clinical meaningful subgroups according to age, sex, body mass index (BMI), and diabetes.ConclusionAn increased NT-proBNP level is associated with an increased risk of MACE in patients with intermediate coronary lesions and may serve as the potential biomarker for risk stratification and treatment decision guidance.

Vericiguat and NT-proBNP in patients with heart failure with reduced ejection fraction: analyses from the VICTORIA trial.

Treatment response to vericiguat, based on baseline N-terminal pro-brain natriuretic peptide (NT-proBNP) subgroups specified in the protocol, was evaluated in the heart failure (HF) VICTORIA trial population by post hoc analysis of combined lower three quartiles [Q1-Q3] vs. the upper quartile [Q4]. VICTORIA participants with available baseline NT-proBNP levels (n=4805; 95.1% of total) were included. Compared with patients in Q1-Q3 (NT-proBNP: Q1, ≤1556pg/mL; Q2, >1556-2816pg/mL; and Q3, >2816-5314pg/mL), patients in Q4 (NT-proBNP: >5314pg/mL) were older (69.2±12.0 vs. 66.6±12.1years), had lower mean ejection fraction (27.2±8.3% vs. 29.5±8.2%; P<0.0001), and were more likely to be in New York Heart Association (NYHA) Class III (51.8 vs. 35.6%) or IV (2.4 vs. 1.0%). Compared with Q1-Q3, patients in Q4 had higher mean Meta-Analysis Global Group in Chronic Heart Failure risk score (27.3±6.6 vs. 23.5±6.4; P<0.0001), had lower mean estimated glomerular filtration rate (eGFR; 51.5±25.5 vs. 65.0±26.8mL/min/1.73m2 ; P<0.0001) and haemoglobin (12.8±2.0 vs. 13.6±1.9g/dL; P<0.0001), and more had atrial fibrillation (48.7% vs. 43.1%; P=0.0007) and were randomized while hospitalized for HF (14.8 vs. 9.9%; P<0.0001). Target dose was achieved in 72.3 and 63.7% of patients in Q1-Q3 and Q4, respectively (P<0.0001). Primary outcome (composite of time to cardiovascular death or first HF hospitalization) rates were 24.5 and 31.7 per 100 patient-years for vericiguat and placebo in Q1-Q3 [hazard ratio (HR) 0.78; 95% confidence interval (CI) 0.69-0.88, P<0.001] and 73.6 and 63.6 in Q4 (HR 1.15; 95% CI 0.99-1.34, P=0.070). Serious adverse events were more frequent in NT-proBNP Q4 (total population) compared with Q1-Q3 (38.3 vs. 32.3%; P=0.0001), driven mainly by the placebo group. Adverse events leading to death were more frequent in Q4 than Q1-Q3 (5.8 vs. 2.4%; P<0.0001). Plasma NT-proBNP may help identify patients with worsening HF with reduced ejection fraction, in whom the beneficial effects of vericiguat may be highest. Patients with highest NT-proBNP values are probably too far advanced, suffering more co-morbidities, or still clinically unstable after decompensation to derive benefit from vericiguat.

NT-proBNP Levels Influence the Prognostic Value of Mineral Metabolism Biomarkers in Coronary Artery Disease.

Background. Mineral metabolism (MM) system and N-terminal pro-brain natriuretic peptide (NT-ProBNP) have been shown to add prognostic value in patients with stable coronary artery disease (SCAD). However, the influence of NT-ProBNP on the prognostic role of MM in patients with SCAD has not been shown yet. The objective of this study is to assess the influence of NT-ProBNP on the prognostic role of MM markers in patients with SCAD. Methods: We analyzed the prognostic value of MM markers (parathormone (PTH), klotho, phosphate, calcidiol (25-hydroxyvitamin D3), and fibroblast growth factor-23) in 964 patients with SCAD and NT-ProBNP > 125 pg/mL vs. patient with NT-ProBNP ≤ 125 pg/mL included in five hospitals in Spain. The main outcome was the combination of death, heart failure, and ischemic events (any acute coronary syndrome, ischemic stroke, or transient ischemic attack). Results: A total of 622 patients had NT-proBNP > 125 pg/mL and 342 patients had NT-ProBNP ≤ 125 pg/mL. The median follow-up was 5.1 years. In the group of NT-proBNP > 125 pg/mL, the patients were older, and there were more females and smokers than in the group of patients with normal NT-proBNP. Additionally, the proportion of patients with hypertension, atrial fibrillation, ejection fraction < 40%, cerebrovascular attack, or prior coronary artery bypass graft was higher in the high NT-proBNP group. In the high NT-proBNP patients, the predictors of poor prognosis were PTH (HR = 1.06 (1.01–1.10), p < 0.001) and NT-proBNP (HR = 1.02 (1.01–1.03), p = 0.011), along with age (HR = 1.039 (1.02–1.06), p < 0.001), prior coronary artery bypass graft (HR = 1.624 (1.02–2.59), p = 0.041), treatment with statins (HR = 0.32 (0.19–0.53), p < 0.001), insulin (HR = 2.49 (1.59–4.09), p < 0.001), angiotensin receptor blockers (HR = 1.73 (1.16–2.56), p = 0.007), nitrates (HR = 1.65 (1.10–2.45), p = 0.014), and proton pump inhibitors (HR = 2.75 (1.74–4.36), p < 0.001). In the NT-proBNP ≤ 125 pg/mL subgroup, poor prognosis predictors were plasma levels of non-high-density lipoprotein (non-HDL) cholesterol (HR = 1.01 (1.00–1.02), p = 0.014) and calcidiol (HR = 0.96 (0.92–0.99), p = 0.045), as well as treatment with verapamil (HR = 11.28 (2.54–50.00), p = 0.001), and dihydropyridines (HR = 3.16 (1.63–6.13), p = 0.001). Conclusion: In patients with SCAD and NT-ProBNP > 125 pg/mL, PTH and NT-ProBNP, which are markers related to ventricular damage, are predictors of poor outcome. In the subgroup of patients with NT-ProBNP ≤ 125 pgm/L, calcidiol and non-HDL cholesterol, which are more related to vascular damage, are the independent predictors of poor outcome. Then, in patients with SCAD, baseline NT-ProBNP may influence the type of biomarker that is effective in risk prediction.

N-terminal pro-brain natriuretic peptide predicts hospitalization for ischemic stroke in Japanese hemodialysis patients.

The association between N-terminal pro-brain natriuretic peptide (NT-proBNP) and stroke in Japanese hemodialysis (HD) outpatients is unclear. Therefore, in this study, we investigate whether high NT-proBNP levels are associated with future stroke events in this population. This was a multicenter prospective observational study with post hoc analysis. Baseline NT-proBNP levels were measured at the first HD session of the week and classified into tertiles (first tertile: < 2255pg/mL; second tertile: ≥ 2255 and < 5657pg/mL; third tertile: ≥ 5657pg/mL). Overall hospitalization-free survival rates were compared using the Kaplan-Meier method. The association between NT-proBNP level and hospitalization for stroke was assessed using the multivariate Cox proportional hazards models. During a 5-year follow-up of 1,229 patients, 103 (8.4%) were hospitalized and 23 (1.9%) died from stroke. The hospitalization-free survival rate for ischemic stroke was lowest in the third tertile (P < 0.01). The crude hazard ratio (HR) of hospitalization was higher in the third tertile compared with the first tertile for both ischemic stroke (HR: 3.92; 95% confidence interval [CI] 2.08-7.37; P < 0.01) and hemorrhagic stroke (HR: 3.75; 95% CI 1.35-10.43; P = 0.01). On multivariate Cox hazard analysis, the adjusted HRs for ischemic stroke were higher in the third tertile. The hospitalization-free survival rates for hemorrhagic stroke and the adjusted HRs did not differ significantly. Elevated NT-proBNP level was associated with hospitalization for ischemic stroke, suggesting that NT-proBNP level is a valid biomarker for predicting hospitalization for ischemic stroke in HD outpatients.

Baroreflex activation therapy with the Barostim™ device in patients with heart failure with reduced ejection fraction: a patient level meta-analysis of randomized controlled trials.

Heart failure with reduced ejection fraction (HFrEF) remains associated with high morbidity and mortality, poor quality of life (QoL) and significant exercise limitation. Sympatho-vagal imbalance has been shown to predict adverse prognosis and symptoms in HFrEF, yet it has not been specifically targeted by any guideline-recommended device therapy to date. Barostim™, which directly addresses this imbalance, is the first Food and Drug Administration approved neuromodulation technology for HFrEF. We aimed to analyse all randomized trial evidence to evaluate the effect of baroreflex activation therapy (BAT) on heart failure symptoms, QoL and N-terminal pro-brain natriuretic peptide (NT-proBNP) in HFrEF. An individual patient data (IPD) meta-analysis was performed on all eligible trials that randomized HFrEF patients to BAT + guideline-directed medical therapy (GDMT) or GDMT alone (open label). Endpoints included 6-month changes in 6-min hall walk (6MHW) distance, Minnesota Living With Heart Failure (MLWHF) QoL score, NT-proBNP, and New York Heart Association (NYHA) class in all patients and three subgroups. A total of 554 randomized patients were included. In all patients, BAT provided significant improvement in 6MHW distance of 49 m (95% confidence interval [CI] 33, 64), MLWHF QoL of -13 points (95% CI -17, -10), and 3.4 higher odds of improving at least one NYHA class (95% CI 2.3, 4.9) when comparing from baseline to 6 months. These improvements were similar, or better, in patients who had baseline NT-proBNP &lt;1600 pg/ml, regardless of the cardiac resynchronization therapy indication status. An IPD meta-analysis suggests that BAT improves exercise capacity, NYHA class, and QoL in HFrEF patients receiving GDMT. These clinically meaningful improvements were consistent across the range of patients studies. BAT was also associated with an improvement in NT-proBNP in subjects with a lower baseline NT-proBNP.

Markers of Inflammation, Oxidative Stress, and Fibrosis in Patients with Atrial Fibrillation.

Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia in clinical practice. The pathogenesis of AF is linked to inflammatory reaction and oxidative stress, which leads to fibrosis of the atria and progression of the disease. The purpose of this study was to define the role of several biomarkers of inflammation, fibrosis, and oxidative stress (OxS). We included 75 patients with paroxysmal/persistent AF, who were admitted for electrical cardioversion or pulmonary vein isolation (PVI). High-sensitivity C-reactive protein (hsCRP), galectin-3 (Gal-3), myeloperoxidase (MPO), oxidized low-density lipoprotein (oxLDL), and N-terminal pro-brain natriuretic peptide (NT-proBNP) were measured before the procedures. We compared the results with those of 75 healthy age-, sex-, and blood pressure-matched individuals. The patients were followed up for 1 year after the intervention to establish the recurrence of AF and its association with the measured markers. Patients with AF had higher MPO (52.6 vs. 36.2 ng/ml, p < 0.001) and NT-proBNP (209.0 vs. 28.0 pg/ml, p < 0.001) compared to healthy subjects. Also, they showed significantly higher levels of hsCRP (1.5 vs. 1.1 mg/l, p = 0.001) and Gal-3 (11.4 vs. 9.7 mg/l, p = 0.003), while there was no difference found in oxLDL (71.5 vs. 71.7 U/l, p = 0.449). MPO (OR = 1.012, p = 0.014), hsCRP (OR = 1.265, p = 0.026), and weight (OR = 1.029, p = 0.013) were independently associated with AF in a multivariable logistic regression analysis. Patients with successful maintenance of sinus rhythm (SR) for one year had lower baseline MPO (40.5 vs. 84.3 ng/ml, p = 0.005) and NT-proBNP (127.5 vs. 694.0 pg/ml, p < 0.001) compared to patients with recurrent AF episodes, but there was no difference in hsCRP, Gal-3, or oxLDL between them. MPO (OR = 0.985, p = 0.010) was independently associated with AF recurrence during the follow-up period when adjusted for cofounders. Patients with AF had increased markers of inflammation and fibrosis, while there was no increase detected in the OxS marker oxLDL. MPO was independently associated with AF in a multivariate model. Inflammatory and fibrotic mechanisms are important factors in electrical and structural remodelling progress in the atria of patients with AF.

The Association of N-Terminal Pro-Brain Natriuretic Peptide With Time to Clinical Worsening in Hispanic Patients With Pulmonary Arterial Hypertension.

BackgroundMeasurement of N-terminal pro-brain natriuretic peptide (NT-proBNP) level is an important parameter in the risk assessment of patients with pulmonary arterial hypertension (PAH). Data about the prognostic value of NT-proBNP in the Hispanic PAH population are lacking. Historically, clinical trials in PAH have only included a minority of Hispanic patients. It has been reported that baseline NT-proBNP levels differ between different ethnicities. Furthermore, NT-proBNP levels can be impacted by declining renal function, making its interpretation difficult regarding clinical decision making.MethodsIn a retrospective single-center cohort analysis, Hispanic patients with PAH had a baseline outpatient NT-proBNP level drawn during a period of clinical stability and were followed for 1 year to monitor for time to clinical worsening (TTCW). The association of baseline NT-proBNP and TTCW was assessed in patients with normal and abnormal renal function.ResultsA total of 26 patients (22%) met the clinical endpoint of clinical worsening. Twenty-seven patients (24%) had chronic kidney disease (CKD). At baseline NT-proBNP levels showed a significant inverse correlation with 6-min walk test (6MWD, r = -0.382, P = 0.02), and a significant positive correlation with renal function (r = 0.273, P = 0.05). NT-proBNP levels did not correlate with age (r = 0.19, P = 0.11) or body mass index (BMI) (r = -0.292, P = 0.061). NT-proBNP levels of > 1,415 ng/L were significantly associated with shorter TTCW (P < 0.01) in all patients and in patients with CKD (P = 0.03). A stepwise increase in NT-proBNP levels by 100 ng/L was associated with a higher risk of meeting the clinical endpoint of TTCW in patients with normal renal function (hazard ratio (HR) = 1.8, P < 0.01) and CKD (HR = 1.5, P < 0.01).ConclusionsIn Hispanic patients with PAH, NT-proBNP is a valuable tool to predict 1-year TTCW, independent of renal function.

Abstract 10497: Predictors of Poor Prognosis in Stable Coronary Artery Disease with and without N-Terminal Probnp Elevation

Background: Mineral Metabolism (MM) system and N-terminal probrain natriuretic peptide (NT-ProBNP) have been shown to add prognostic value in stable coronary artery disease (SCAD). However, the influence of NT-ProBNP on the prognostic role of MM in SCAD has not been shown yet Methods: We analyzed the prognostic value of MM markers (parathormone [PTH], klotho, phosphate, calcidiol [25-hydroxyvitamin D3], and fibroblast growth factor-23) in 964 pts. with SCAD and NT-ProBNP&gt;125 pg/ml vs pts. with NT-ProBNP≤125 pg/ml included in five hospitals of Spain. The main outcome was the combination of death, heart failure, and ischemic events (any acute coronary syndrome, ischemic stroke, or transient ischemic attack). Results: 622 pts. had NT-proBNP&gt;125 pg/ml and 342 pts. had NT-ProBNP≤125 pg/ml. Median follow-up was 5.1 years. In the group of NT-proBNP&gt;125 pg/ml patients were older, and there were more females and smokers than in pts. with normal NT-proBNP.In high NT-proBNP pts., the predictors of poor prognosis were PTH [HR=1.00 (1.00-1.00) p&lt;0.001] and NT-proBNP [HR=1.006 (1.00-1.01) p=0.011], along with age [HR=1.039 (1.02-1.06) p&lt;0.001], prior coronary artery by-pass graft [HR=1.624 (1.02-2.59) p=0.041], treatment with statins [HR= 0.315 (0.19-0.53) p&lt;0.001], insulin [HR=2.490 (1.59-4.09) p&lt;0.001], angiotensin receptor blockers [HR= 1.726 (1.16-2.56) p=0.007], nitrates [HR= 1.645 (1.10-2.45) p=0.014], and proton pump inhbitors [HR= 2.754 (1.74-4.36) p&lt;0.001]. In the NT-proBNP≤125 pg/ml subgroup, poor prognosis predictors were plasma levels of non-high-density lipoprotein (non-HDL) cholesterol [HR=1.01 (1.00-1.02) p=0.014] and calcidiol [HR= 0.96 (0.92-0.99) p=0.045], as well as treatment with verapamil [HR=11.28 (2.54-50.00) p=0.001], and dihydropyridines [HR= 3.16 (1.63-6.13) p=0.001], Conclusion: In pts. with SCAD and NT-ProBNP&gt;125 pg/ml, PTH and NT-ProBNP, that are markers related with ventricular damage, are predictors of poor outcome. In the subgroup of pts. with NT-ProBNP≤125 pgm/l, calcidiol and non-HDL cholesterol, more related to vascular damage, are the independent predictors of poor outcome. Then, in pts. with SCAD, baseline NT-ProBNP may influence the type of biomarker that should be used for risk prediction.

Prognostic Value of N-Terminal Pro-Brain Natriuretic Peptide and High-Sensitivity Troponin T Levels in the Natural History of Transthyretin Amyloid Cardiomyopathy and Their Evolution after Tafamidis Treatment.

Background: We assesse the evolution and prognostic value of N-terminal pro-brain natriuretic peptide (NT-proBNP) and high-sensitivity troponin T (cTnT-HS) in transthyretin amyloid cardiomyopathy (ATTR-CA) before and after tafamidis treatment. Methods and Results: 454 ATTR-CA patients without tafamidis (Cohort A) and 248 ATTR-CA with tafamidis (Cohort B) were enrolled. Event-free survival (EFS) events were death, heart transplant, or acute heart failure. In Cohort A, 27% of patients maintained NT-proBNP < 3000 ng/L and 14% cTnT-HS < 50 ng/L at 12 months relative to baseline levels. In Cohort B, the proportions were 49% and 29%, respectively. In Cohort A, among the 333 patients without an increased NT-proBNP > 50% relative to baseline EFS was extended compared to the 121 patients with an increased NT-proBNP > 50% (HR: 0.75 [0.57; 0.98]; p = 0.032). In Cohort A, baseline NT-proBNP > 3000 ng/L and cTnT-HS > 50 ng/L and a relative increase of NT-proBNP > 50% during follow-up were independent prognostic factors of EFS. The slopes of logs NT-proBNP and cTnT-HS increased with time before and stabilized after tafamidis. Conclusion: ATTR-CA patients with increasing NT-proBNP had an increased risk of EFS. Tafamidis stabilize NT-proBNP and cTnT-HS increasing, even if initial NT-proBNP levels were >3000 ng/L. Thus suggesting that all patients, irrespective of baseline NT-proBNP levels, may benefit from tafamidis.

The Predictive Value of N-Terminal Probrain Natriuretic Peptide for Infection in Patients With Acute Myocardial Infarction.

Background: Infections increase the risk of poor outcomes in patients with ST-elevation myocardial infarction (STEMI) undergoing percutaneous coronary intervention (PCI). However, predicting patients at a high risk of developing infection remains unclear. Moreover, the value of N-terminal probrain natriuretic peptide (NT-proBNP) for predicting infection is still unknown. Thus, we aimed to assess the relationship between NT-proBNP and the following development of infection, and clinical adverse outcomes in patients with STEMI undergoing PCI.Methods: STEMI patients undergoing PCI were consecutively enrolled from January 2010 to July 2016 and divided into groups according to baseline NT-proBNP levels: tertiles T1 (<988 pg/mL), T2 (988–3520 pg/mL), and T3 (≥3520 pg/mL). The primary endpoint was infection during hospitalization.Results: A total of 182 (27%) patients developed in-hospital infection. The incidence of infection increased from T1 to T3 (10.5, 17.7, and 54.5%, P < 0.001). NT-proBNP was an independent risk factor (adjusted odds ratio = 1.39, 95% confidence interval (CI) = 1.12–1.73, P = 0.003) and presented accurately predicting infection (area under curve = 0.774). Multivariate cox analysis showed that NT-proBNP was a significant risk factor for major adverse clinical events (MACE) at follow-up (adjusted HR = 1.92, 95% CI = 1.61–2.29, P < 0.001).Conclusion: The baseline NT-proBNP level has a good predictive value for infection and MACE in STEMI patients undergoing PCI.

N-terminal pro brain natriuretic peptide predicts both all-cause and cardiovascular disease mortality in Japanese hemodialysis patients.

The association between N-terminal pro brain natriuretic peptide (NT-proBNP) level and long-term mortality in Japanese hemodialysis patients has not been fully assessed. This prospective, multicenter study included 1428 hemodialysis outpatients. Baseline NT-proBNP levels were measured at the first hemodialysis session of the week and participants were followed for 5years. The areas under the curve were calculated from receiver operating characteristic curves. Groups determined by quartiles of baseline NT-proBNP level were assessed by the Kaplan-Meier method and log-rank test. The association between NT-proBNP level and mortality was assessed using multivariate Cox proportional hazards models. During the 5-year follow-up, we observed 370 deaths and 256 censored cases. The areas under the curve of pre-hemodialysis NT-proBNP for all-cause mortality and cardiovascular disease mortality after 1year were 0.75 and 0.78, respectively, and significantly greater than the areas under the curve at the 3- and 5-year follow-up. Cut-off values for all-cause mortality and cardiovascular disease mortality after 1year were 4550 and 5467ng/L, respectively (sensitivity: 82% and 81%; specificity: 59% and 64%). Kaplan-Meier survival analysis showed that the group with pre-hemodialysis NT-proBNP ≥ 8805ng/L had increased all-cause mortality (P < 0.001) and cardiovascular disease mortality (P < 0.001). Finally, multivariate Cox analysis showed that NT-proBNP level was associated with all-cause mortality (P < 0.001) and cardiovascular disease mortality (P = 0.004) independently from other clinical parameters. NT-proBNP is a useful marker to predict both all-cause and cardiovascular disease mortality in hemodialysis patients.