NT-proBNP Research Articles

Clinical Performance of an N-Terminal Pro-B-Type Natriuretic Peptide Assay in Acute Heart Failure Diagnosis.

We evaluated the Vitros® Immunodiagnostic Products N-terminal pro B-type natriuretic peptide (NT-proBNP) II assay for aiding in diagnosis of heart failure (HF) in patients with acute dyspnea. Serum concentrations of NT-proBNP were measured in patient samples from 20 emergency departments across the United States. Study endpoints included sensitivity, specificity, likelihood ratios, and predictive values for diagnosis of acute HF according to age-stratified cutoffs (450, 900, and 1800 pg/mL), and a rule-out age-independent cutoff (300 pg/mL). Additional measures were area under the curve (AUC) for receiver operating characteristic (ROC) curves. Results were also interpreted in patient subgroups with relevant comorbidities, and gray zone/intermediate assay values. Of 2200 patients, 1095 (49.8%) were diagnosed with HF by clinical adjudication. Sensitivity and specificity for Vitros NT-proBNP II ranged from 84.0% to 92.1%, and 81.4% to 86.5%, respectively, within and across age groups, and positive predictive values were 80.4% to 85.7%. Using the rule-out cutoff, the negative predictive value was 97.9%, with a negative likelihood ratio of 0.02. In subgroups with comorbidities potentially affecting NT-proBNP concentrations, sensitivities ranged from 82.6% to 89.5%, and AUCs for ROC curves were 0.899 to 0.915. The Vitros NT-proBNP II assay demonstrated excellent clinical performance using age-stratified cutoffs along with other clinical information for supporting diagnosis of HF, and can rule out HF with a high negative predictive value using the age-independent cutoff. The assay retained utility in patient subgroups with conditions that influence NT-proBNP concentration, and for those with gray zone results. NCT03548909.

Circulating microRNA-409-5p and USP7 are associated with left ventricular remodeling in patients with acute myocardial infarction

BackgroundOur previous study demonstrated that microRNA-409-5p (miR-409-5p) and its target ubiquitin-specific protease 7 (USP7) were involved in hypoxia-induced cardiomyocyte injury and ischemic left ventricular remodeling (LVR) in rats. This study aimed to probe into the relationship between plasma miR-409-5p and USP7 levels and LVR and dysfunction in patients with acute myocardial infarction (AMI).MethodsSixty patients with acute myocardial infarction (AMI) and 60 cases with chronic coronary syndrome (CCS) were enrolled. The clinical characteristics, echocardiographic/serum parameters of LVR, and circulating miR-409-5p and USP7 mRNA levels between the two groups and between admission and 6 weeks after discharge were compared. The correlations between circulating miR-409-5p/USP7 levels and serum/echocardiographic parameters were analyzed.ResultsThe demographic characteristics of the AMI group and CCS group were comparable. Patients with AMI admitted to the study displayed significantly higher levels of plasma N-terminal pro-brain natriuretic peptide (NT-proBNP) and growth stimulation expressed gene 2 (ST2), along with a greater left ventricular end-systolic volume (LVESV). Conversely, their left ventricular ejection fraction (LVEF), global longitudinal strain (GLS), and global radial strain (GRS) were significantly lower compared to patients with CCS. These changes were normalized 6 weeks after discharge. Circulating miR-409-5p levels at admission were significantly decreased while circulating USP7 mRNA expression levels were significantly increased in patients with AMI compared with those with CCS (both P < 0.01). However, these changes were restored 6 weeks after discharge (both P < 0.01). Moreover, circulating miR-409-5p and USP7 mRNA levels showed varying correlations with GLS, GRS, LVESV, LVEF, and NT-proBNP in patients with AMI but not in those with CCS. Additionally, circulating miR-409-5p and USP7 levels predicted the incidence of LVR and major adverse cardiovascular events (MACE) after AMI.ConclusionSerum miR-409-5p and USP7 may influence the occurrence and evolution of LVR and left ventricular dysfunction after AMI.

Effects of new hypoglycemic drugs on patients with heart failure: a systematic review and network meta-analysis.

Currently, there is no relevant study comparing sodium-dependent glucose transporter 2 inhibitors (SGLT2i), glucagon-like peptide-1 receptor agonists (GLP-1RA), and dipeptidyl peptidase inhibitor (DPP4i) head to head to evaluate their comprehensive impact on heart failure patients. We conducted a comprehensive literature search across multiple databases. Utilizing the risk of bias tool from the Cochrane Collaboration, the methodological quality of included studies was critically assessed and potential publication bias was examined via funnel plots. All results are presented as mean difference; 95% confidence interval (MD; 95% CI). The network meta-analysis indicated that in regards to left ventricular function, there is a big difference in the left ventricular ejection fraction (LVEF) of Empagliflozin 25mg (13.64; 0.26, 27.01) compared to Canagliflozin 100mg; and significant differences in the left ventricular end-diastolic volume (LVEDV) and left ventricular end-systolic volume (LVESV) of Dapagliflozin 10mg (-0.76; -1.27, -0.25 and -0.95; -1.86, -0.05), Vildagliptin 50mg (-1.05; -1.47, -0.63 and -1.12; -2.19, -0.05), and Sitagliptin 100mg (-1.34; -2.31, -0.38 and -1.89; -3.50, -0.27) compared to Empagliflozin 10mg. In terms of the quality of life, there are significant differences in the N-terminal pro-B-type natriuretic peptide (NT-proBNP) and the Quality of life score of Sitagliptin 100mg (408.08; 213.59, 602.57 and 3.74; 1.57, 5.92) compared to Dapagliflozin 5mg. In terms of the cardiovascular outcome events, there is a significant difference in the heart failure rehospitalization rate of Dapagliflozin 10mg (0.45; 0.25, 0.82) and Empagliflozin 10mg (0.48; 0.28, 0.81) compared to Liraglutide 1.8mg. Further significant differences are found in the all-cause mortality of Dapagliflozin 10mg (0.81; 0.66, 0.98) compared to Vildagliptin 50mg; the cardiovascular death of Albiglutide 30mg (0.49; 0.28, 0.86) compared to Exenatide 2mg; and the arrhythmic events of Liraglutide 1.8mg (0.49; 0.26, 0.90) compared to Empagliflozin 10mg. The network meta-analysis of SGLT2i, GLP-1RA, and DPP4i as a class of drugs showed that GLP-1RA is superior to SGLT2i in improving LVEF and reducing myocardial infarction/acute coronary syndrome, whereas DPP4i is superior to SGLT2i in improving LVEDV and LVESV. GLP-1RA is superior to SGLT2i in improving LVEF and reducing myocardial infarction/acute coronary syndrome, whereas DPP4i is superior to SGLT2i in improving LVEDV and LVESV. Key message What is already known on this topic-It has been confirmed that three new hypoglycemic drugs have a protective effect on the cardiovascular system. Studies have shown that sodium-dependent glucose transporter 2 inhibitors (SGLT2i) can improve cardiovascular outcomes and enhance the quality of life of heart failure patients. Currently, SGLT2i is widely used in the clinical treatment of heart failure, and related studies have shown that glucagon-like peptide-1 receptor agonists (GLP-1RA) and dipeptidyl peptidase inhibitor (DPP4i) also play important roles in the treatment of heart failure. What this study adds-However, there is no relevant research on whether these drugs' clinical efficacy is dose-dependent. How this study might affect research, practice, or policy-This study included different doses of hypoglycemic drugs and used a network meta-analysis method to comprehensively evaluate the effects of three hypoglycemic drugs on heart function, quality of life, and prognosis in heart failure patients, providing a basis for clinical practice.

Randomized trial of early exercise rehabilitation and its effects on patients with acute coronary syndrome

To assess the psychological and physiological benefits of early exercise rehabilitation in patients with acute coronary syndrome (ACS). Among 559 ACS-diagnosed patients at Fuzhou University Affiliated Provincial Hospital from January to December 2021, 200 eligible participants were assigned to two groups. The control group received standard care, while the experimental group received early exercise rehabilitation in addition to standard care. The outcomes measured included changes in depression levels (PHQ-9), fasting blood glucose, and troponin I (TnI) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels. Data were analyzed using SPSS, with t tests and chi-square tests for group comparisons. In comparison to the control group, the experimental group demonstrated significant improvements in PHQ-9 scores (P < 0.001) and lower fasting blood glucose levels before discharge (P = 0.046). Additionally, the experimental group had notably reduced TnI levels at 72 h after admission (P = 0.001), especially among non-diabetic NSTEMI patients over 60 years old, who showed decreased TnI levels at the 48-hour mark (P = 0.016). However, there were no significant differences in NT-ProBNP change values between the two groups (P > 0.05). Subgroup analysis revealed enhanced outcomes in the intervention group for ACS patients without smoking or drinking history and no heart failure (P = 0.025,P = 0.014,P = 0.018). Early exercise rehabilitation has notable benefits for ACS patients, including reduced depression, improved blood glucose control, and enhanced myocardial protection, especially in nondiabetic NSTEMI patients aged 60 and above.

Longitudinal and cross-sectional associations of NT-proBNP with kidney function and chronic kidney disease: results from KORA cohort studies

Abstract Background Chronic kidney disease (CKD) and cardiovascular disease (CVD) exhibit a bidirectional and complex relationship, and share common risk factors and mechanisms of disease development. Thus, important CVD-related biomarkers, such as N-terminal prohormone of B-type natriuretic peptide (NT-proBNP), may serve as a biomarker for CKD development. Purpose We aimed to investigate the cross-sectional and longitudinal associations of NT-proBNP with kidney function and CKD in data from two population-based cohort studies. Methods We included 5854 men and women, aged 25-74 years, from the Cooperative Health Research in the Region of Augsburg (KORA) cohort studies S3 and S4, and their 1-2 subsequent follow-up surveys, with a median follow-up time of 9.4 and 13.4 years, respectively. Kidney function was assessed by 3 estimated glomerular filtration rate (eGFR) assessments, calculated using creatinine (eGFRcr), cystatin C, and combined creatinine and cystatin C. Serum NT-proBNP was logarithmically transformed followed by Z-score standardization and categorized into 4 groups (G1-4), &amp;lt;48.6, 48.6-125, 125-300, and ≥300 pg/ml. In cross-sectional analysis, linear regression and logistic regression were used to estimate β/odds ratio (OR) and their 95% confidence intervals (CIs) of continuous eGFR or prevalent CKD. For longitudinal analysis of repeated eGFR measurements during follow-up (5854 participants, 11870 observations), linear mixed-effects models were used. For incident CKD associations, interval-censored Cox regression models were performed in participants free of CKD at baseline. Results In cross-sectional analyses, higher NT-proBNP levels were associated with lower eGFR and higher prevalence of CKD across all 3 eGFR assessments. For example, results based on eGFRcr showed that the fully-adjusted β (95% CIs) for per 1 SD increase in log-transformed NT-proBNP were -1.03 (-1.42, -0.64) and -7.01 (-8.93, -5.09) 60 ml/min/1.73m2 for G4 compared to G1, respectively. Corresponding OR (95% CIs) were 2.22 (1.81, 2.74) and 13.8 (5.76, 36.4), respectively. In longitudinal analyses, participants with higher baseline NT-proBNP had a faster decline in eGFR during follow-up. The fully-adjusted β (95% CIs) for 5-year eGFRcr decline were -0.67 (-0.87, -0.47) per 1 SD increase, and -0.37 (-0.79, 0.05), -1.53 (-2.18, -0.88), -4.24 (-5.57, -2.90) 60 ml/min/1.73m2/year for G2-4. Higher NT-proBNP levels were associated with higher incident CKD risks. For associations with incident creatinine-based CKD, hazard ratio (95% CIs) were 1.16 (1.00, 1.33) per 1 SD increase and 1.03 (0.77, 1.38), 1.07 (0.75, 1.52), and 1.81 (1.07, 3.04) for G2-4. Conclusions We found associations of higher NT-proBNP with lower kidney function and higher CKD prevalence. Moreover, higher baseline NT-proBNP levels were associated with faster kidney function decline and higher incident CKD risks. Our findings indicate the potential utility of NT-proBNP as a biomarker of kidney health.Figure 1.Cross-sectional associationsFigure 2.Longitudinal associations

Clinical application of biomarkers in obstructive hypertrophic cardiomyopathy: insights from SEQUOIA-HCM

Abstract Background Multiple studies show that circulating cardiac biomarkers, N-terminal pro-B type natriuretic peptide (NT-proBNP) and high sensitivity cardiac troponin I (hs-cTnI) are associated with key pathophysiological processes and clinical outcomes in obstructive hypertrophic cardiomyopathy (oHCM). Herein we describe the impact of aficamten on cardiac biomarkers in SEQUOIA-HCM (NCT05186818). Purpose In this pre-specified analysis, we describe associations between baseline NT-proBNP and hs-cTnI concentrations and assess the relationship between changes after treatment with aficamten and trial endpoints. Methods Patients with oHCM in NYHA Class II-III, were randomized 1:1 to 24 weeks of daily aficamten (5–20 mg, n=142) or placebo (n=140). Aficamten dose was adjusted to achieve Valsalva left ventricular outflow tract gradient (LVOT-G) &amp;lt;30 mmHg while maintaining left ventricular ejection fraction (LVEF) ≥50%. Peak oxygen consumption (pVO2) was measured by cardiopulmonary exercise testing at baseline and week 24. Cardiac biomarkers were measured at baseline, each dose titration (weeks 2, 4, and 6), every 4 weeks during treatment and after 4 weeks drug washout. Multivariable regression analysis was used to identify significant predictors of baseline biomarker values. Joint modeling and mediation analysis was used to determine how much of the treatment effect was indirectly mediated by NT-proBNP and hs-cTnI. Results In 282 symptomatic oHCM patients (mean age 59 years, 41% female), the median (IQR) NT-proBNP was 788 ng/L (346, 1699) and hs-cTnI was 12 ng/L (9, 27). At baseline, LVOT-G modestly correlated with NT-proBNP, rho = 0.26 (p&amp;lt;0.001) but not hs-cTnI, rho = 0.06 (p=0.36). Predictors of baseline biomarker values are summarized in Table 1. Compared to placebo, aficamten treatment was associated with an early relative reduction from baseline at week 8 in NT-proBNP (-79% (95% CI -83%, -76%, p&amp;lt;0.001) and in hs-cTnI -41% (-49%, -32%), p&amp;lt;0.001. This magnitude of change persisted to week 24 with biomarker return to baseline after aficamten washout (Figure 1). The mediation analysis suggested that NT-proBNP reduction over the 24-week treatment period reflected 101% (41%, 195%) of aficamten’s effect on pVO2. In contrast hs-cTnI reduction reflected 3% (-18%, 30%) of aficamten’s effect on pVO2. Conclusions Concentrations of NT-proBNP and hs-cTnI are associated with clinically relevant echocardiographic variables in oHCM. Compared with placebo, aficamten treatment markedly reduced plasma NT-proBNP and hs-cTnI concentrations, evident from week 2 and persisting until the end of treatment. NT-proBNP reduction may link LVOT-G with reduced exercise capacity in oHCM. These data support the use of biomarkers as a tool for managing patients with oHCM in order to monitor response to aficamten therapy.Effect of aficamten on biomarkersPredictors of baseline biomarkers

Multi-biomarker approach for predicting cardiac magnetic resonance parameters at 30 days after ST-segment elevation myocardial infarction

Abstract Background Prior data showed associations of circulating Proprotein Convertase Subtilisin / Kexin type 9 (PCSK9) and inflammatory/anti-fibrotic Cellular Communication Network factor 1 (CCN1) at index ST-segment elevation acute myocardial infarction (STEMI) with left ventricular ejection fraction at 6 and 12 months, respectively and for CCN1 also with infarct size. Purpose PCSK-9, CCN1 and reference biomarkers high-sensitivity Troponin T (hsTNT) and N-terminal pro-brain natriuretic peptide (NTproBNP) were measured in patients from the CLEVER-ACS trial (clinicaltrials.gov NCT01529554) at presentation with STEMI and correlated with clinically relevant cardiac magnetic resonance (CMR) parameters at 30 days. Methods Associations between baseline biomarkers (PCSK-9, CCN1, hsTNT, NTproBNP) and CMR parameters at 30 days were evaluated using Spearman correlation and linear regression analysis (dichotomised at their median). Receiver operating characteristic (ROC) and area under the curve (AUC) were determined for significant values based on correlation analysis; AUC &amp;gt; 0,7 considered relevant. CMR parameters comprised left ventricular structural and functional parameters including scar mass and microvascular obstruction. Results We identified 56 STEMI patients (mean age 61.7 ± 11.2 (SD) years) who completed 30 days follow-up with biomarker data. Among biomarkers, significant associations with CMR parameters were only found for hsTNT, and NTproBNP. The strongest associations were found for left ventricular ejection fraction (LVEF; hsTNT RSp =-0.66; NTproBNP RSp =-0.57), left ventricular scar (LVSCAR; hsTNT RSp =0.58; NTproBNP RSp =0.56) and scar mass (SM; hsTNT RSp =0.65; NTproBNP RSp =0.55). Conversely, left ventricular end-diastolic volume index (LVEDVI; hsTNT RSp =0.47; NTproBNP RSp =0.32), left ventricular end-systolic volume index (LVESVI; hsTNT RSp =0.51; NTproBNP RSp =0.39) and microvascular obstruction (MVO; hsTNT RSp =0.34; NTproBNP RSp =0.34) were significantly, albeit only modestly associated. ROC and AUC analysis yielded relevant associations of biomarkers with CMR parameters LVEF (hsTNT=0.79; NTproBNP=0.81), LVSCAR (hsTNT=0.84; NTproBNP=0.76) and scar mass (hsTNT=0.83; NTproBNP=0.78). Furthermore, relevant associations of biomarkers with CMR were found for LVEDVI (hsTNT=0.79; NTproBNP=0.72), LVESVI (hsTNT=0.84; NTproBNP=0.72) and MVO (hsTNT=0.72; NTproBNP=0.71). Conclusion Baseline levels of hsTNT and NT-proBNP are strong predictors for functional and dimensional CMR parameters of the left ventricle including clinically relevant imaging surrogates of myocardial injury shortly after STEMI.ROC LVEF

Association between dyspnea, chest pain, nt-probnp and cardiac impairment in people with cystic fibrosis

Abstract Background Cystic fibrosis (CF) is an autosomal recessive disease affecting multiple organs. Emerging evidence indicates an elevated risk of cardiovascular complications in people with CF (pwCF), with some studies implicating CF-related cardiomyopathy as an underlying mechanism. Whether screening for cardiac symptoms and N-terminal pro B-type natriuretic peptide (NT-proBNP) levels may aid in identifying cardiac impairment in pwCF remains unknown. Purpose To assess prevalence of dyspnea and chest pain in pwCF and investigate whether symptoms and NT-pro-BNP are predictive of cardiac impairment. Methods We interviewed 104 adult pwCF and 104 age- and sex-matched controls from the general population about symptoms of dyspnea and chest pain. All participants were examined with transthoracic echocardiography and NT-proBNP. Cardiac impairment was defined as left ventricular (LV) ejection fraction (LVEF) &amp;lt;50%, LV global longitudinal strain (GLS) &amp;lt; 16% or presence of diastolic dysfunction. Results Chest pain was more frequent in pwCF than in controls: (29% vs. 1%, p&amp;lt;0.001), although primarily characterized as atypical and non-exertional chest pain (27%). PwCF also suffered more from dyspnea than controls (89% vs. 18%, p&amp;lt;0.001) (Figure 1) and more pwCF had abnormal cardiac function compared to controls (44% versus 22%, p&amp;lt;0.001). Median NT-proBNP in pwCF was 50.0 pg/ml (40.7; 100.8) and increasing NT-proBNP level was associated with decreasing FEV1 (L) (estimate: -0.008, p&amp;lt;0.001). NT-proBNP level was not associated with neither dyspnea nor chest pain (p=0.60 and p=0.15, respectively). PwCF with dyspnea did not differ from those without on clinical or echocardiographic parameters. However, pwCF with chest pain had lower absolute GLS compared to pwCF without (17.4% vs.18.5%, p=0.026). Neither dyspnea nor chest pain was more frequent in pwCF with cardiac impairment versus normal cardiac function (54% vs. 39%, p=0.17 and 29% vs. 28%, p=0.91, respectively). Decreasing absolute GLS was associated with increased odds of chest pain (OR 1.25, 95% CI 1.02; 1.53, p=0.030) (Figure 2). Neither dyspnea or chest pain alone, nor in combination with NT-proBNP were able to predict abnormal cardiac function. While dyspnea and chest pain combined showed a slight improvement in sensitivity and positive predictive value for diagnosing cardiac impairment, the combination of symptoms and increased NT-proBNP did not enhance diagnostic accuracy. Conclusions In this cross-sectional study, dyspnea and atypical, non-exertional chest pain were common symptoms in adult pwCF. While abnormal cardiac function was prevalent in pwCF, neither symptoms, NT-proBNP nor a combination of these were associated with increased odds of cardiac impairment. Dyspnea and chest pain, though prevalent, are multifactorial in pwCF and do not seem to serve as sensitive markers of cardiac impairment, even when combined with NT-proBNP level.

Usefulness of preoperative NT-proBNP for prediction of acute heart failure, perioperative myocardial infarction/injury and mortality after non-cardiac surgery

Abstract Background Predicting cardiac complications after non-cardiac surgery is challenging. Purpose to determine the predictive accuracy of N-Terminal Pro–B-Type Natriuretic Peptide (NT-proBNP) and, to assess the utility of existing NT-proBNP cutoffs of the 2021 ESC Guidelines for the diagnosis of acute and chronic heart failure for prediction of postoperative acute heart failure (pAHF), perioperative myocardial infarction/injury (PMI) and mortality following non-cardiac surgery. Methods we prospectively determined preoperative NT-proBNP concentrations in consecutive patients at high cardiac risk undergoing inpatient non-cardiac surgery. Uni- and multivariable regression models were constructed to test the association between NT-proBNP concentrations and the outcomes (pAHF, PMI, 30-day and one-year mortality), using NT-proBNP as a continuous variable. We further stratified NT-proBNP into 5 categories according to guidelines (&amp;lt;125 pg/ml, 125 to 299pg/ml, 300 to 900 pg/ml, 901 to 1800pg/ml and &amp;gt;1800 pg/ml). Receiver operating characteristic curves were constructed to determine the predictive value of NT-proBNP. Results Among the 2,334 cases included, pAHF occurred in 83 (3.6%), PMI in 381 (17%), 45 (2.5%) patients died within 30 days and 179 (10%) within one year. After adjusting for confounders, NT-proBNP concentrations were independent predictors of pAHF (adjusted hazard ratio [aHR] 1.8 [95%CI, 1.5-2.1], p&amp;lt;0.001), PMI (aHR 1.3 [95%CI, 1.2-1.4],p&amp;lt;0.001) and 30 day/one year mortality (aHR 1.6[95%CI, 1.3-2.0], p&amp;lt;0.001)/aHR 1.5 [95%CI 1.4-1.7], p&amp;lt;0.001). By quintiles, higher the NT-proBNP levels were strongly associated with adverse outcome (Figure). Accuracy of preoperative NT-proBNP for prediction of pAHF was excellent (area under the curve [AUC] 0.825) and better than accuracy of the Revised Cardiac Risk Index score (AUC 0.692, p&amp;lt;0.001), whereas accuracy of NT-proBNP for prediction of PMI (AUC 0.654) and mortality (AUC 0.787) was only moderate. Conclusion NT-proBNP concentrations are independent predictors of pAHF, PMI and short and long-term mortality following non-cardiac surgery. Stratifying NT-proBNP concentrations using current recommended cut-offs could help to further determine the magnitude of the risk, mainly of pAHF.

N-terminal prohormone of brain natriuretic peptide predicts recurrent cardiovascular events in patients with acute coronary syndrome both in the acute and post-discharge setting: a TRACER substudy

Abstract Background N-terminal prohormone of brain natriuretic peptide (NT-proBNP) is a circulating peptide released by the heart in response to increased wall tension and stretching, for example, occurring during myocardial and/or atrial dysfunction. NT-proBNP is a diagnostic and prognostic marker in patients with heart failure but might also have prognostic utility in the acute phase of patients with acute coronary syndrome (ACS) and at one month after ACS. Purpose To assess the prognostic value of NT-proBNP over time in patients with ACS both in the acute setting and when re-assessed after one month. Methods The TRACER study randomized 12,944 patients with non-ST-segment elevation ACS (NSTE-ACS) to treatment with vorapaxar vs. placebo. Plasma samples for biomarker analyses were obtained at randomization (median 21 hours after hospital admission) in 6,800 patients and at an outpatient visit after one month in 5,313 patients. NT-proBNP was analysed using the Elecsys electrochemiluminescence immunoassays method. The primary composite endpoint in this substudy was the one-year risk of cardiovascular (CV) mortality, myocardial infarction, or ischaemic stroke. Associations between continuous natural log-transformed NT-proBNP levels and outcomes were assessed using Cox regression models accounting for study treatment and established risk factors. Results The median concentration of NT-proBNP during hospitalization for ACS and after one month was 496 ng/L and 264 ng/L, respectively. Higher age, female sex, a history of heart failure, and lower body mass index were independently associated with higher levels of NT-proBNP among patients in the acute setting, with renal disease also being an important factor after one month. The composite outcome of CV mortality, MI, or ischaemic stroke occurred in 901 patients (incidence rate 10.1 per 100 person-years) included at baseline and in 381 patients (incidence rate 5.4 per 100 person-years) included at one month. Higher circulating levels of NT-proBNP were independently associated with a higher risk of the composite endpoint at baseline (adjusted hazard ratio with 95% confidence interval comparing the third vs. the first sample quartile: 1.25 [1.03 – 1.51]) and at one month (1.56 [1.15 – 2.11]) (Figure 1 and 2). Incorporating NT-proBNP at baseline into a model with other established risk factors increased the concordance index of the multivariable model from 0.656 to 0.660 (p &amp;lt; 0.001), and after one month, from 0.711 to 0.733 (p &amp;lt; 0.001). These findings remained consistent across the various components of the composite endpoint. Conclusions In patients with ACS, the level of NT-proBNP is an indicator of increased risk of CV outcomes both in the acute setting and, even more pronounced, one month after the index ACS. Measuring NT-proBNP provided incremental prognostic information beyond established risk factors, both in the acute and post-discharge settings.Fig 1.NT-proBNP quartile groupsFig 2.NT-proBNP and CV outcome

Left atrial volumetric-mechanical coupling index as a marker of subclinical primary heart involvement in systemic sclerosis

Abstract Background Primary heart involvement in systemic sclerosis (SSc) is a common yet often clinically silent marker of poor prognosis. Up to 80% of patients have histopathological evidence of heart involvement, highlighting the need for better screening and diagnostic methods. N-terminal pro-brain natriuretic peptide (NTproBNP), a well-established cardiac biomarker, is often increased in patients with SSc, but with a not fully understood mechanism. Meanwhile, left atrial volumetric-mechanical coupling index (LACI), a new echocardiographic parameter, has been shown to predict cardiovascular outcomes in heart failure patients and the general population, but it has not been studied in SSc. Purpose To identify new echocardiographic parameters, particularly related to left atrial volume and function, as markers of increased NTproBNP in SSc patients without overt heart involvement. Methods Consecutive SSc patients without overt heart disease referred for routine cardiac screening underwent 2D and 3D transthoracic echocardiography, including atrial and ventricular strain analysis. LACI was calculated by both 2D and 3D echocardiography as the ratio between the left atrial volume index and the tissue-Doppler-imaging septal a’ velocity. Patients with significant structural and functional changes suggestive of systolic or diastolic dysfunction or pulmonary hypertension, and those with impaired global left ventricular strain were excluded. Logistic regression, Pearson correlation coefficients, and area under the receiver-operating characteristic curve (AUC) are used to analyze the association and predictive power of LACI for elevated NTproBNP. Results A total of 36 SSc patients (55±10 years old; 34 (94%) women; mean disease duration 14±11 years) were included. Sixteen (44.4%) had diffuse cutaneous involvement (dcSSc). Seventeen (47%) patients had increased NTproBNP levels (i.e. &amp;gt;125 pg/mL). Among all tested variables, 3D LACI had the best correlation with NTproBNP values (r = 0.63, p&amp;lt;0.001). A 3D LACI of &amp;gt;2 associated with NTproBNP of &amp;gt;125 pg/mL (odds ratio 7.33 [95%CI 1.38-38.8]; p=0.01) and predicted these increased values with a sensitivity of 76.9% and a specificity of 81.2% (AUC 0.78). NTproBNP was also correlated with 2D LACI (r=0.55, p&amp;lt;0.001), peak left atrial longitudinal strain (r=-0.42, p=0.01), and left atrial contraction strain (r=0.48, p=0.005). Compared to patients with limited cutaneous involvement, those with dcSSc had higher NTproBNP values (250±139.6 vs 107.2±110.9 pg/mL, p=0.001), higher 3D LACI values (2.6±0.9 vs 1.9±0.5, p=0.02), with similar left atrial and ventricular strain parameters. Conclusion Left atrial volumetric-mechanical coupling index assessed by 3D echocardiography is significantly associated with and predictive of elevated NTproBNP levels in SSc patients without overt heart disease and may be a potentially useful non-invasive marker for screening for early subclinical heart involvement in SSc patients.

Up-titration of Guideline Directed Medical Therapy (GDMT) and the occurrence of side effects in Heart Failure with reduced Ejection Fraction (HFrEF)

Abstract Background The ESC Guidelines recommend early, full-dose use of heart failure (HF) medications to enhance survival, but real-world application often faces delays and inconsistencies. Clinicians often fear side effects during up-titration to the recommended target dose (TD), i.e. hypotension, bradycardia, renal impairment, and hyperkalemia (HK). The dependency of side effects during dose escalation from the severity of HF remains unclear. Purpose This study aimed to evaluate the relationship between the occurrence of side effects during up-titration of HF medication and HF severity reflected by N-terminal pro B-type natriuretic peptide (NT-proBNP). Methods 425 patients with HFrEF and a complete data set of patient characteristics, medications and laboratory values at baseline (BL), 2 months (2M), and 6 months (6M) were included from our outpatient HF unit's prospective registry. Significant side effects were defined as: systolic blood pressure (SBP) &amp;lt;90mmHg, heart rate (HR) &amp;lt;50 beats per minute (bpm), potassium (K) &amp;gt;5.0mmol/l or K &amp;gt;5,5mmol/l and estimated glomerular filtration rate (eGFR) &amp;lt;30ml/min/1.73m2. Patients were categorized into three risk groups based on their NT-proBNP levels, i.e. low-risk with NT-proBNP &amp;lt;1000pg/ml, medium-risk with NT-proBNP 1000-2000pg/ml or high-risk with NT-proBNP &amp;gt;2000pg/ml. The occurrence of side effects was recorded and the development compared among the HF risk groups. Results Figure 1 shows up-titration of HF medication. Mean daily dosages of betablockers (BB), mineralocorticoid receptor antagonists (MRA) and renin-angiotensin-system inhibitors (RASi) increased significantly during follow-up (BL vs 2M and BL vs 6M, p&amp;lt;0.001 for all). The majority of patients received ≥50% of the recommended TDs at 6M (89% for BB, 83% for MRA, 88% for RASi and 91% for total mean TDs ≥50%), and the achieved daily dosages at 6M were largely comparable across the HF risk groups at 6M, except for RASi (p=0.030). Figure 2 depicts the side effects. Side effects developed almost exclusively at short-term within 2M except for lower SBP (Figure 2A). Newly developed side effects occurring after up-titration (2B) were even more rare and predominantly occurred within the highest NT-proBNP group. The occurrence of hypotension and bradycardia was infrequent and comparable within the HF risk groups. Renal dysfunction (at 6M p=0,041) and HK occurred predominantly in higher risk patients (HK at 2M p=0,001 and at 6M p&amp;lt;0,001). Conclusions Up-titration of HF medications is highly feasible, particularly in low- and medium-risk patients. Despite rare side effects such as hyperkalemia and renal impairment, up-titration remains unimpeded, especially in patients with NT-proBNP levels below 2000pg/ml. These findings emphasize the safety of up-titration in HF.

Prognostic implications of N-terminal pro-brain natriuretic peptide in patients with Non-ST segment elevation myocardial infarction

Abstract Background Limited data exist regarding prognostic implications of N-terminal pro-Brain Natriuretic Peptide (NT-proBNP) in patients with non-ST segment elevation myocardial infarction (NSTEMI) who underwent percutaneous coronary intervention (PCI). Objectives The current study sought to evaluate the prognostic implications of NT-proBNP in patients with NSTEMI who underwent PCI. Methods Among a total of 13,104 patients from a nationwide, multicenter, and prospective registry of the Korea Acute Myocardial Infarction Registry-National Institutes of Health (KAMIR-NIH), a total of 3,083 patients with NSTEMI who underwent PCI were selected. The selected patients were classified according to the initial NT-proBNP value (cut-off value of NT-proBNP, 700 pg/ml). Primary endpoint was major adverse cardiovascular events (MACE) at 3 years, a composite of all-cause death, recurrent myocardial infarction (MI), unplanned repeat revascularization, and admission for heart failure. Results Among the study population, 1,813 patients (58.8%) were in the low NT-proBNP group (&amp;lt;700 pg/ml) and 1,270 patients (41.2%) were in the high NT-proBNP group (≥700 pg/ml). The high NT-proBNP group showed significantly higher risk of MACE than the low NT-proBNP group (29.5% vs 12.3%; adjusted hazard ratio [HR], 1.69; 95% confidence interval [CI], 1.39-2.07; P&amp;lt;0.001), mainly driven by higher risk of cardiac death or admission for heart failure (15.6% vs. 2.2%; adjusted HR, 2.98; 95% CI, 2.03-4.40; P&amp;lt;0.001). These results were consistent after confounder adjustment by propensity score matching (HR, 1.56; 95% CI, 1.21-2.02; P=0.001) and inverse probability weighting analysis (HR, 1.54; 95% CI, 1.19-2.00; P=0.001). Conclusion In patients with NSTEMI who underwent PCI, elevated initial NT-proBNP level was associated with higher risk of MACE at 3 years, mainly driven by the higher risk of cardiac death or admission for heart failure. The current results suggest that the initial NT-proBNP level may have a clinically significant prognostic value in NSTEMI patients undergoing PCI.

Machine learning to improve the performance of natriuretic peptides across age groups for the diagnosis of acute heart failure

Abstract Background Guidelines recommend N-terminal pro-B-type natriuretic peptide (NT-proBNP) thresholds for the diagnosis of acute heart failure but performance of these thresholds in different age groups is uncertain and could be improved using machine learning methods that incorporate age as a continuous measure. Purpose To evaluate the diagnostic performance of guideline-recommended NT-proBNP thresholds for different age groups and a validated decision-support tool using machine learning for the diagnosis of acute heart failure. Methods NT-proBNP concentrations and the output from the CoDE-HF decision-support tool that uses machine learning to combine NT-proBNP and age as continuous variables with other patient variables were determined in 10,369 patients (median age 73 [interquartile range 59-82]) with suspected acute heart failure pooled from fourteen studies. The diagnostic performance of guideline-recommended NT-proBNP uniform rule-out thresholds (300 pg/mL), and age-stratified rule-in thresholds (450 pg/mL, 900 pg/mL and 1,800 pg/mL for &amp;lt;50, 50-75 and ≥75 years, respectively) and CoDE-HF were evaluated using random effects meta-analysis across patient age groups. Results Overall, 43.9% (4549/10 369) of patients had an adjudicated diagnosis of acute heart failure. The negative predictive value (NPV) of the rule-out threshold of 300 pg/mL was lower in patients with increasing age (NPV 88.2% [confidence interval (CI) 83.5-91.8%] ≥75 years versus 98.9% [97.6-99.5%] &amp;lt;50 years) (Figure 1). Conversely, the positive predictive value (PPV) of age stratified rule-in thresholds was lower in younger patients (PPV 61.8% [55.9-67.4%] &amp;lt;50 years versus 80.5 % [71.1-87.4%] ≥75 years) (Figure 2). CoDE-HF had improved diagnostic performance compared to NT-ProBNP thresholds for all age groups, with the lowest NPV and PPV being 96.4% (93.8-97.9%) and 78.6% (59.8-90.0%), respectively. Conclusion The diagnostic performance of guideline recommended thresholds of NT-proBNP to rule-in and rule-out acute heart failure varies significantly with age. A decision-support tool that incorporates NT-proBNP with age as continuous variables provides a more consistent and accurate approach.Figure 1.Negative predictive valueFigure 2.Positive predictive value

Screening for stage B heart failure in Type 2 diabetes: natriuretic peptide screening alone misses echocardiographic abnormalities

Abstract Background Heart failure (HF) often manifests as the first cardiac event in individuals with type 2 diabetes mellitus (T2DM). International guidelines recommend natriuretic peptide (NP) screening for stage B/ pre-HF in asymptomatic individuals with T2DM, with echocardiography reserved for those with elevated NPs ("NP-gated" echo approach). Whether this strategy misses individuals with echocardiographic abnormalities despite normal NPs is not fully understood. Purpose To assess the proportion of individuals with T2DM who will be classified as Stage B HF based on biomarker and echocardiography, using independent and combined screening approaches. Methods We utilised the Performance of NT-proBNP In risk Stratification for Cardiovascular Events and mortality in patients with diabetes [PISCES] study (n=765, mean age 62±9 years, 62% men), which enrolled patients with T2DM with no HF. All patients underwent laboratory-based N-terminal pro-B-type NP (NT-proBNP) testing and a point-of-care artificial intelligence echocardiography (Us2.ai). Abnormal echocardiography was defined as left ventricular ejection fraction &amp;lt;50%, left ventricular mass index ≥115(male) or ≥95g/m2(female), left atrial volume index&amp;gt;34 in sinus rhythm or &amp;gt;40mL/m2 in atrial fibrillation, relative wall thickness (RWT) &amp;gt;0.42, E/e' &amp;gt;9, peak tricuspid regurgitation velocity &amp;gt;2.8m/s, pulmonary arterial systolic pressure &amp;gt;35mmHg. Patients with T2DM were classified into either (1) Stage B(biomarker) with elevated NT-proBNP (≥125pg/mL) and normal echocardiography, or (2) Stage B(echo) with abnormal echocardiography and normal NT-proBNP, or (3) Stage B(biomarker+echo) with elevated NT-proBNP and abnormal echocardiography or (4) no abnormalities. Results Among asymptomatic patients with T2DM, the highest proportion of individuals were in Stage B(echo) (43%), followed by those with no abnormalities (37%), Stage B(biomarker+echo) (15%) and Stage B(biomarker) (5%). Patients with Stage B(echo) (vs. no abnormalities) were older (62.5 vs 59.8 years), had a higher prevalence of hypertension (78.4 vs. 72.4%), higher systolic blood pressure (135 vs. 128 mmHg), higher RWT and higher E/e’ (p&amp;lt;0.001 for all). Individuals in Stage B(biomarker+echo) (versus no abnormalities) were older, had a longer duration of T2DM, higher prevalence of hypertension, atrial fibrillation, prior CVD, highest NT-proBNP levels, lowest eGFR levels, and more echocardiography abnormalities (higher RWT and E/e’). Patients identified as Stage B(biomarker) (versus no abnormalities) had a longer duration of T2DM, higher NT-proBNP levels, higher prevalence of comorbidities and comparable echocardiographic measures. Conclusion Among asymptomatic patients with T2DM, a significant proportion have subclinical cardiac abnormalities despite a lack of diagnostic NP elevation. Instead of NP-gated echocardiography, an integrated approach using both NT-proBNP and AI echocardiography may improve the early detection of Stage B HF.

Relationship between NT-proBNP, echocardiographic abnormalities and functional status in patients with subclinical diabetic cardiomyopathy

Abstract Background Persons with diabetes are at risk for developing a cardiomyopathy through several pathophysiological mechanisms independent of traditional risk factors for heart failure. Among those with so-called diabetic cardiomyopathy (DbCM), the relationship between natriuretic peptides, cardiac structural abnormalities and functional capacity is largely unknown. Purpose This study aimed to evaluate associations between NT-proBNP concentrations, clinical characteristics, echocardiographic findings, health status and activity, and outcomes from cardiopulmonary exercise testing Methods The Aldose Reductase Inhibition for Stabilization of Exercise Capacity in Heart Failure Trial (ARISE-HF) trial is evaluating the effects of AT-001, a novel aldose-reductase inhibitor in participants with DbCM without a prior history of heart failure (1). Participants were included if they had a known diagnosis of type 2 diabetes and age ≥60 (or ≥45 with a duration of diabetes of ≥10 years or estimated glomerular filtration rate ≤60 mL/min/1.73m2). Participants were required to have evidence of one of: structural cardiac abnormality, elevated cardiac biomarkers, or impaired exercise tolerance, defined as a peak oxygen uptake (VO2) ≤75% of predicted. In this prespecified subgroup analysis of the ARISE-HF trial, 685 participants with baseline echocardiography data, laboratory investigations, and functional assessment were included. Participants were stratified by N-terminal pro-B type natriuretic peptide (NT-proBNP) quartiles, and correlation with echocardiographic and functional parameters were assessed using Spearman correlation test. Results The mean age of participants was 67.4 years and 50% were female. The mean duration of type 2 diabetes was 14.5 years with a mean hemoglobin A1c of 6.98. The median NT-proBNP was 71 (Q1, Q3: 33, 135) ng/L. No association was observed between NT-proBNP concentrations and echocardiographic parameters of either diastolic or systolic dysfunction including global longitudinal strain, left ventricular ejection fraction, left ventricular mass index, left atrial volume index, E/e’, or right ventricular systolic pressure (Figure 1). In contrast, NT-proBNP was significantly correlated with components of the Kansas City Cardiomyopathy Questionnaire (P&amp;lt;0.001), the Physical Activity Scale in the Elderly (P=0.004), duration of cardiopulmonary exercise testing (P&amp;lt;0.001), peak VO 2 (P&amp;lt;0.001), and ratio of minute ventilation/carbon dioxide production (P=0.002; Figure 2). Conclusion Among highly selected patients with subclinical DbCM, elevated NT-proBNP concentrations are associated with worse health status, lower activity levels, and reduced functional capacity, but not with cardiac structural abnormalities. These findings suggest that regardless of cardiac structural abnormalities, biomarker concentrations reflect important deterioration in functional capacity in affected individuals.

CILP1 and NTproBNP in pulmonary hypertension and right ventricular pressure overload: a translational experimental study

Abstract Introduction Cartilage intermediate layer protein 1 (CILP1) has emerged as a novel marker of right ventricular (RV) dysfunction in pulmonary hypertension (PH), although there is still little evidence on its role in different scenarios of RV pressure overload. The aim of our study was to analyze CILP1 as a biomarker of RV remodeling and PH severity, and compare it with N-terminal pro-brain natriuretic peptide (NTproBNP), in different experimental models of RV pressure overload. Methods Three different experimental models of RV pressure overload compared to a sham procedure were evaluated in 24 Yucatan pigs: chronic postcapillary PH by pulmonary vein banding (M1, n=6); chronic PH by aorto-pulmonary shunting (M2, n=6); RV pressure overload by PA banding (thus without PH) (M3, n=6); and sham procedure (M0, n=6). Animals were evaluated at 8 months after surgery by right heart catheterization, cardiac magnetic resonance (CMR), and blood/histological sampling. Levels of CILP1 and NTproBNP at the RV myocardium and blood were determined with dedicated ELISA and compared among groups by Wilcoxon test with Bonferroni correction. Associations between biomarkers and RV performance indices and pulmonary arterial pressure (PAP) were assessed with Spearman correlation test. Results M1 animals developed chronic postcapillary PH with normal left ventricular (LV) performance and RV maladaptive hypertrophy (RV fibrosis and systolic dysfunction). M2 animals developed chronic precapillary PH associated with LV dilatation and RV maladaptive hypertrophy. On contrast, M3-animals developed severe RV pressure overload (without PH) and hypertrophy but maintained normal RV systolic function. CILP1 and NTproBNP levels were moderately correlated (R=0.56, p=0.002). CILP1 levels in RV myocardium and plasma were significantly higher in M1, whereas NTproBNP plasma levels were significantly higher in M2 (Figure 1). CILP1 in plasma and RV myocardium significantly correlated with PAP, while myocardial CILP1 levels also correlated with RV extracellular volume (RV-ECV) by CMR (Figure 2). NTproBNP myocardial levels correlated with RV ejection fraction and RV-ECV and plasmatic levels correlated with PAP (Figure 2). Conclusions CILP1 levels were increased in the presence of PH and isolated RV dysfunction, whereas NTproBNP levels were increased in the model of PH, RV dysfunction and LV remodeling. Myocardial levels of both peptides correlated with diffuse fibrosis, estimated by CMR, whereas plasmatic levels of both biomarkers correlated with PAP. This suggests that CILP1 may be a more specific marker of RV dysfunction in PH, being less dependent of LV parameters.CILP1 and NTproBNP levels among modelsCorrelation with PAP &amp; RV remodeling

Cardiac biomarkers can detect and track subclinical HIV-associated myocardial disease in newly diagnosed people living with HIV

Abstract Background Cardiovascular disease (CVD) in people living with HIV (PLWH) remains poorly understood, and the profile of disease differs between high-income and low- and middle-income settings[1]. Subclinical cardiovascular abnormalities may be present at the time of HIV diagnosis and serve as potential substrate for future CVD[2]. Biochemical markers are fundamental in cardiac evaluation, and various novel assays have recently been discovered. Purpose To assess the presence and evolution of subclinical myocardial disease, we prospectively assessed the hearts of newly diagnosed PLWH and matched, HIV-uninfected controls using cardiac biomarkers and correlated our findings with cardiovascular magnetic resonance imaging (CMR). Methods Newly diagnosed, antiretroviral treatment (ART) naïve PLWH were recruited along with HIV uninfected, age- and sex-matched controls in the Western Cape Province of South Africa. All participants underwent measurement of high-sensitivity cardiac troponin T (hs-cTnT), N-terminal pro-B-type natriuretic peptide (NT-proBNP), soluble ST2 (sST2), Galectin-3, and a CMR study with multiparametric mapping. The HIV group started ART and was re-evaluated 9 months later. The cardiac biomarkers and their correlation with CMR parameters were evaluated in, and between groups. Results Compared with controls (n=22), hs-cTnT (4.0 ng/l vs 5.1 ng/l; p=0.004) , NT-proBNP (23.2 ng/l vs 40.8 ng/l; p=0.02), and Galectin-3 (6.8 ng/ml vs 9.0 ng/ml; p=0.002) were all significantly higher in the ART naïve group (n=73). After 9 months of ART, hs-cTnT (5.1 ng/l vs 4.3 ng/l; p=0.02) and NT-proBNP (40.8 ng/l vs 28.5 ng/l; p=0.03) both decreased significantly, and a trend of decrease was seen in sST2 (16.5 ng/ml vs 14.8 ng/l; p=0.08). Galectin-3 did not demonstrate decrease over time (9.0 ng/ml vs 8.8 ng/ml; p=0.6). The cardiac biomarkers that showed the best correlation with CMR measurements native T1, T2, and ECV, were NT-proBNP (rs≥0.4, p&amp;lt;0.001) and Galectin-3 (rs≥0.3, p&amp;lt;0.01). Conclusion Our cardiac biomarker data supports the presence of subclinical myocardial injury, remodelling, and fibrosis at HIV diagnosis and ART had a positive influence on these blood markers. It remains unclear if the underlying pathological processes were fully addressed by ART. The elevation of Galectin-3 despite ART may be indicative of ongoing cardiac remodelling that may incur future risk of CVD, and necessitates further study. The ability of cardiac biomarkers to detect and track tissue abnormalities diagnosed with CMR, showed promise. With additional research, this could lead to improvements in screening and monitoring myocardial abnormalities, even in CMR-limited settings.

Clinical Implications of NT-proBNP trajectory following Sacubitril/Valsartan initiation

Abstract Introduction Serum N-terminal pro–B-type natriuretic peptide (NT-proBNP) values after initiating Sacubitril/Valsartan is considered as a favorable prognostic factor, and widely used for risk stratification in patients with heart failure (HF). However, the relationship between the trajectory of serially measured NT-proBNP values and cardiovascular events in patients with HF who are treated with Sacubitril/Valsartan remains uncertain. Purpose This study aimed to reveal the prognostic association of an NT-proBNP trajectory after initiating Sacubitril/Valsartan and subsequent cardiovascular outcomes. Methods and Results A Japanese nationwide multicenter study was conducted on HF patients who initiated Sacubitril/Valsartan. Out of the 995 patients enrolled, we excluded 561 patients who were undergoing assessment of BNP or who lacked a complete set of NT-proBNP measurement. Finally, 434 patients included this study, and were divided into three groups based on NT-proBNP trajectory as follows; the ‘sustained-responder’ group (n = 129, 30%) : which exhibited a reduction of NT-proBNP by ≥10% at 1 month and further reduction of ≥10% at 3 months; and the ‘transient-responder’ group (n = 161, 37%), with ≥10% reduction at 1 month but not at 3 months; and the ‘non-responder’ group (n = 144, 33%), which did not achieve ≥10% reduction at 1 month. The mean age was 68 years, with females comprising 29%. In the ‘sustained-responder’ group, the age was significantly younger, and the duration of heart failure was significantly shorter. There were no significant differences in the mean systolic blood pressure, mean Sacubitril/Valsartan dose at each measurement points among the 3 groups. During follow-up of 456 (IQR, 371-549) days, the primary endpoint, which was either cardiovascular death or hospitalization of HF occurred in 78 of 434 patients (18%). The Kaplan-Meier analysis showed that the ‘sustained responder’ group experienced significantly lower event rate among the 3 groups (Log-rank p&amp;lt;.001). Additionally, an analysis that set a landmark time at 3 months post-initiation of Sacubitril/Valsartan showed that the ‘sustained-responder’ group experienced significantly fewer events than the ‘transient-responder’ group (Log-rank p=0.039) (Figure.1). Also, the ‘sustained responder’ was observed to have a better prognosis in a subgroup with LVEF&amp;lt;50%, but not in patients with LVEF ≥50%. (p value for interaction=0.035) (Figure.2). Conclusions This study revealed that sustained reduction of NT-proBNP was associated with a reduced risk of cardiovascular death or hospitalization for HF. The periodic NT-proBNP monitoring and the patterns of NT-proBNP during treatment with Sacubitril/Valsartan may be helpful in optimizing HF therapy and understanding the prognosis of HF.Figure.1Figure.2

Changes in N-terminal pro b-type natriuretic peptide according to SGLT2 inhibitor utilization patterns in patients hospitalized for decompensated heart failure: a prospective cohort study

Abstract Introduction Sodium-glucose cotransporter-2 (SGLT2) inhibitors have found success in treating patients with chronic heart failure (HF) across the entire spectrum of left ventricular ejection fraction (EF). Their benefits may also extend to patients with acute HF decompensation, as they may aid effective decongestion. Purpose This study aims to present the various patterns in changes of N-terminal pro b-type natriuretic peptide (NT-proBNP) according to SGLT2 inhibitor use in patients hospitalized for acute HF decompensation. Methods In this prospective cohort study, we enrolled consecutive patients hospitalized for HF decompensation during a 4-month period in a cardiology department. Prior medical history and cardiovascular risk factors were recorded. The patterns in SGLT2 inhibitor use were noted and patients were classified into three groups; Group 1 (No SGLT2 inhibitor use/Discontinuation), Group 2 (Prior SGLT2 inhibitor use and continuation), and Group 2 (SGLT2i-naïve and initiation). Categorization according to left ventricular (EF) to HF with reduced EF (HFrEF), HF with mildly reduced EF (HFmrEF), and HF with preserved EF (HFpEF) was also performed. Moreover, estimated glomerular filtration rate (eGFR) was used as an estimate of renal function. Results In this analysis, 159 patients were included (median age: 79 years old, male sex: 64.8%, median duration of hospitalization: 6 days). In this population, 67.9% of the patients were not receiving a SGLT2 inhibitor on admission. Concerning demographic and clinical variables (Figure 1), there were no major differences in age, sex distribution, history of diabetes mellitus, dyslipidemia, and atrial fibrillation, as well as in renal function. Group 2 patients had a lower prevalence of arterial hypertension compared to Group 3 (36.6% vs. 52.6%, p&amp;lt;0.05). Moving to the changes in NTproBNP (Figure 2), we observed that patients who did not use SGLT2 inhibitors and did not initiate them during hospitalization had negligible changes in NTproBNP, either as an absolute change (Group 1: 506 (8792) pg/ml vs. Group 2: -5610 (9461) pg/ml vs. Group 3: -3602 (4409) pg/ml, p=0.001) or as percentage change (Group 1: -2.1 (63.4) % vs. Group 2: -30.3 (39.0) % vs. Group 3: -38.3 (41.5) %, p=0.001), compared to the rest of the study population who were already taking SGLT2 inhibitors or initiated them during hospitalization. Conclusion In this study we found NTproBNP, a widely used biomarker of congestion and prognosis in HF, was significantly reduced in decompensated HF patients receiving SGLT2 inhibitors, with the greatest change being observed in those being treatment-naïve prior to admission. These findings further highlight the role of this drug class even in the acute phase of the disease.Figure 1Figure 2