B-type Natriuretic Peptide Concentrations Research Articles

NT-proBNP for Predicting All-Cause Death and Heart Transplant in Children and Adults with Heart Failure.

Plasma N-terminal prohormone B-type natriuretic peptide (NT-proBNP) concentration is a heart failure (HF) biomarker in adults and children. Its prognostic value for HF-related events has been established only in adults. Therefore, weaimed to test the hypothesis that plasma NT-proBNP concentrations predicted the risk of heart transplantation or death in children with HF. We studied the medical records of 109 children with HF enrolled in the IBM Watson Explorys database and from 150 children enrolled in the Pediatric Cardiomyopathy Registry (PCMR). Nonlinear regression was used to assess the relationship between plasma NT-proBNP concentrations and the risk of events in the two cohorts. All children in the PCMR cohort had dilated cardiomyopathy. The Explorys cohort also included children with congenital cardiovascular malformations. Median plasma NT-proBNP concentrations were 1250pg/mL and 184pg/mL in the Explorys and PCMR cohorts, respectively. The percentage of deaths/heart transplantations was 7%/22%, over 2years in the Explorys cohort and 3%/16% over 5years in the PCMR cohort. Mean estimates of plasma NT-proBNP concentration indicative of half-maximum relative risk for events (EC50 values) at 2 and 5years were 3730pg/mL and 4199pg/mL, respectively, values both close to the mean of 3880pg/mL established for adults with HF. The plasma NT-proBNP concentration is suitable for estimating relative risk of mortality and heart transplantation in children with HF, independent of etiology and shows similar relations to clinical outcomes as in adults, indicating its likely value as a surrogate marker both for adult and pediatric HF.ClinicalTrials.gov Identifiers: NCT00005391 (May 26, 2000), NCT01873976 (June 10, 2013).

Importance of B-Type Natriuretic Peptide in the Detection of Patients With Structural Heart Disease in a Primary Care Setting.

Early detection and intervention for preclinical heart failure (HF) are crucial for restraining the potential increase in patients with HF. Thus, we designed and conducted a single-center retrospective cohort study to confirm the efficacy of B-type natriuretic peptide (BNP) for the early detection of preclinical HF in a primary care setting.Methods and Results: We investigated 477 patients with no prior diagnosis of HF who were under the care of general practitioners. These patients were categorized into 4 groups based on BNP concentrations: Category 1, 0 pg/mL≤BNP≤35 pg/mL; Category 2, 35 pg/mL<BNP≤100 pg/mL; Category 3, 100 pg/mL<BNP≤200 pg/mL; and Category 4, BNP >200 pg/mL. There was a marked and statistically significant increase in the prevalence of preclinical HF with increasing BNP categories: 19.9%, 57.9%, 87.5%, and 96.0% in Categories 1, 2, 3, and 4, respectively. Compared with Category 1, the odds ratio of preclinical HF in Categories 2, 3, and 4 was determined to be 5.56 (95% confidence interval [CI] 3.57-8.67), 23.70 (95% CI 8.91-63.11), and 171.77 (95% CI 10.31-2,861.93), respectively. Measuring BNP is a valuable tool for the early detection of preclinical HF in primary care settings. Proactive testing in patients at high risk of HF could play a crucial role in addressing the impending HF pandemic.

Myocardial Injury by COVID-19 Infection Assessed by Cardiovascular Magnetic Resonance Imaging - A Prospective Multicenter Study.

This prospective multicenter study assessed the prevalence of myocardial injury in patients with COVID-19 using cardiac magnetic resonance imaging (CMR).Methods and Results: We prospectively screened 505 patients with moderate to severe COVID-19 disease from 7 hospitals in Japan. Of these patients, 31 (mean [±SD] age 63.5±10.4 years, 23 [74%] male) suspected of myocardial injury, based on elevated serum troponin or B-type natriuretic peptide concentrations either upon admission or 3 months after discharge, underwent CMR 3 months after discharge. The primary endpoint was the presence of myocardial injury, defined by any of the following: (1) contrast enhancement in the left or right ventricle myocardium on late gadolinium enhancement CMR; (2) left or right ventricular dysfunction (defined as <50% and <45%, respectively); and (3) pericardial thickening on contrast enhancement. The mean (±SD) duration between diagnosis and CMR was 117±16 days. The primary endpoint was observed in 13 of 31 individuals (42%), with 8 (26%) satisfying the modified Lake Louise Criteria for the diagnosis of acute myocarditis. This study revealed a high incidence of myocardial injury identified by CMR in patients with moderate to severe COVID-19 and abnormal findings for cardiac biomarkers.

Exploration of the Potential Biomarker FNDC5 for Discriminating Heart Failure in Patients with Coronary Atherosclerosis.

Coronary atherosclerosis leading to ischemic artery disease is one of the etiological factors to develop heart failure (HF). This study aimed to investigate potential biomarkers for discriminating HF in atherosclerotic patients. This study included 40 consecutive atherosclerotic patients who underwent angiography. Concentrations of B-type natriuretic peptide (BNP), fibronectin type III domain containing 5 (FNDC5), and Phosphodiesterase 9A (PDE9A) were measured in 20 atherosclerotic patients with HF symptoms/signs and 20 without HF symptoms/signs. Circulating BNP levels were elevated, while FNDC5 levels were reduced in atherosclerotic patients with HF symptoms/signs compared to those without HF symptoms/signs. Pearson correlation analysis showed a significant correlation between FNDC5 and BNP. Receiver Operating Characteristics analysis indicated that both FNDC5 and BNP were able to discriminate HF in atherosclerotic patients. Our findings suggest that FNDC5, along with BNP, has independent value as a biomarker for discriminating HF in patients with coronary atherosclerosis.

Cyanidin prevents cardiomyocyte apoptosis in mice after myocardial infarction.

Myocardial infarction is a worldwide disease with high morbidity and mortality and a major cause of chronic heart failure, seriously affecting patients' quality of life. Natural medicine has been used to cure or prevent cardiovascular disease for decades. As a natural flavonoid, anthocyanidin has been used to treat many diseases due to its antioxidative, anti-inflammatory, and other properties. A mouse model (C57BL/6) weighing 30-40g was utilized to induce myocardial infarction by ligating the left anterior descending coronary artery. Cyanidin (30mg/kg) was administered orally to mice for four weeks. A variety of assessments were used to evaluate cardiac function. The gene expression was measured using RNAseq and Western blot. Histological changes in myocardial tissue were assessed using staining techniques, including Masson, Hematoxylin Eosin (HE), and transmission electron microscopy. Tunnel staining was implemented as a method to detect cellular apoptosis. For the quantification of B-type natriuretic peptide (BNP) and atrial natriuretic peptide (ANP) in the serum, an enzyme-linked immunosorbent assay (ELISA) was employed. Furthermore, autodock simulation was executed in order to assess the interaction between cyanidin and a subset of genes. Cyanidin treatment inhibited myocardial cell apoptosis, improved cardiac function, and reduced serum concentrations of BNP and atrial natriuretic peptide ANP, as well as mitigated histological cardiac tissue damage. Cyanidin also inhibited the activity of matrix metalloproteinases (MMP2/9) and Fibronectin 1 (Fn1). Cyanidin improves heart function and reduces myocardial damage in mice after MI. Furthermore, cyanidin can prevent cardiomyocyte apoptosis. These effects are most likely caused by suppression of MMP9/2 and control of the Akt signaling pathway, suggesting an appropriate therapeutic target.

Assessment of Pazopanib-Related Heart Failure in Patients With Advanced Soft Tissue Sarcoma - A Single Institute Analysis.

Heart failure (HF) is one of the potential adverse events of pazopanib treatment for soft tissue sarcoma (STS), but detailed reports of such HF cases are scarce. This study determined the incidence and risk factors of HF following pazopanib treatment for STS at our Institute and the clinical outcomes.Methods and Results:This study retrospectively analyzed the cases of STS patients treated with pazopanib (n=151) between 2012 and 2020. HF occurred in 6 patients (3.9%) at the median onset of 137 (range 14-468) days after the treatment initiation. When their HF was diagnosed, pazopanib was interrupted in all 6 patients. No patients experienced HF-related death, and HF development was not a significant factor for poor overall survival. The cumulative doses of anthracyclines (>225 mg/m2) before pazopanib initiation (83% vs. 37%, P=0.031), pazopanib initiation at age ≥60 years (83% vs. 35%, P=0.026), and the baseline B-type natriuretic peptide (BNP) concentration (≥50 pg/mL) before pazopanib (67% vs. 11%, P=0.002) initiation were predictive factors for post-pazopanib treatment HF. The study findings highlight the effect of past anthracycline exposure and baseline BNP for pazopanib-associated HF. Although the study patients' clinical outcomes were generally favorable, periodic monitoring of cardiac function using ultrasonic echocardiography or serum markers is essential to detect events early and begin therapeutic intervention appropriately under a cardiologist's instructions.

Long-Term Treatment With Sacubitril/Valsartan in Japanese Patients With Chronic Heart Failure and Reduced Ejection Fraction - Open-Label Extension of the PARALLEL-HF Study.

The PARALLEL-HF study assessed the efficacy and safety of sacubitril/valsartan vs. enalapril in Japanese patients with chronic heart failure with reduced ejection fraction (HFrEF). This open-label extension (OLE) assessed long-term safety with sacubitril/valsartan.Methods and Results: This study enrolled 150 patients who received sacubitril/valsartan 50 or 100 mg, b.i.d., in addition to optimal background heart failure (HF) therapy. A dose level of sacubitril/valsartan 200 mg, b.i.d., was targeted by Week 8. At OLE baseline, higher concentrations of B-type natriuretic peptide (BNP) and urine cGMP, and lower concentrations of N-terminal pro B-type natriuretic peptide (NT-proBNP), were observed in the sacubitril/valsartan core group (patients who received sacubitril/valsartan in both the core and extension study) than in the enalapril core group (patients who received enalapril in the core study and were then transitioned to sacubitril/valsartan). The mean exposure to study drug was 98.9%. There was no trend of worsening of HF at Month 12. No obvious changes in cardiac biomarkers were observed, whereas BNP and urine cGMP increased and NT-proBNP decreased in the enalapril core group, which was evident at Weeks 2-4 and sustained to Month 12. Long-term sacubitril/valsartan at doses up to 200 mg, b.i.d., has a positive risk-benefit profile; it was safe and well tolerated in Japanese patients with chronic HFrEF.

Intrapartum trends of NT-proBNP and hs-cTnT in patients with severe features of preeclampsia

BackgroundPreeclampsia with severe features (SPE) is a multisystem syndrome associated with long-term cardiovascular morbidity. Serum concentrations of N-terminal B-type natriuretic peptide (NT-proBNP) and high sensitivity cardiac troponin-T (hs-cTnT) are sensitive markers of cardiac stretch and ischemia, respectively. ObjectiveOur aim was to examine NT-proBNP and hs-cTnT in patients with SPE during labor. We hypothesized that patients with severe preeclampsia would have increased serum concentrations of these analytes as compared with normotensive laboring patients.Study Design.This was a prospective cohort study of intrapartum patients with SPE and normotensive controls. Patients were recruited at the time of SPE diagnosis or admission to the labor unit, and those with medical conditions that could predispose to baseline cardiac dysfunction were excluded. Serum from venous blood was collected for NT-proBNP and hs-cTnT measurement at three time points: 0–2 h, 4 h, and 12 h after admission. A mixed random effects regression model was used to compare analyte levels at each time point and to compare trends over time. The primary outcome was NT-proBNP concentration at each collection time point in patients with severe preeclampsia as compared to normotensive controls. Power analysis yielded a goal sample of 25 patients with a 12 h and at least 1 other sample in each arm. Two-tailed P values less than 0.05 were considered statistically significant. P value adjustment for multiple comparisons was performed. ResultsOf 78 patients analyzed, 36 had severe preeclampsia and 42 were normotensive controls with 25 in each cohort having a 12 h and at least 1 other sample. The NT-proBNP trend was significantly different in the two cohorts (P < 0.001). After adjustment for multiple comparisons, the mean serum concentration of NT-proBNP was elevated in the severe preeclampsia group at 0–2 and 4 h, but not at 12 h. After similar adjustment, detectable serum concentrations of hs-cTnT were more frequent in patients with severe preeclampsia at all three timepoints. ConclusionIntrapartum serum concentrations of NT-proBNP were elevated nearly twofold in patients with SPE when compared with normotensive controls, with the most pronounced differences found during early labor. Detectable but low serum concentrations of hs-cTnT were more common in women with severe preeclampsia as compared with normotensive controls. These findings suggest cardiac dysfunction with SPE may be present at the time of admission and contribute to features of maternal cardiovascular morbidity and mortality.

Clinical effect of renal dysfunction on diagnostic and prognostic accuracy of B-type Natriuretic Peptide and N-terminal Pro-B-type Natriuretic Peptide for acute heart failure

Abstract Background Acute heart failure (AHF) continues to have unacceptable high rates of mortality and morbidity. Therefore, accurate and rapid diagnosis of AHF is crucial for the early initiation of effective treatment. Previous studies have shown that plasma concentrations of B-type natriuretic peptide (BNP) and N-terminal pro-BNP (NT-proBNP) increase with declining renal function and that renal dysfunction seems to decrease the accuracy of BNP and NT-proBNP in the diagnosis of AHF. Purpose We aimed to directly compare the diagnostic and prognostic accuracy of BNP and NT-proBNP in patients presenting with acute dyspnea, including the effect of renal function. Methods This prospective diagnostic study enrolled unselected patients presenting with acute dyspnea to the emergency department. The final diagnosis was centrally adjudicated by two independent cardiologists using all information including imaging and follow-up. BNP and NT-proBNP plasma levels were determined at presentation. 360 days all-cause mortality was the primary prognostic end point. Results Among 1579 patients, acute heart failure (AHF) was the adjudicated final diagnosis in 865 patients (54.8%). Plasma concentrations of both BNP and NT-proBNP were significantly higher in AHF as compared to other causes of acute dyspnea (both p&amp;lt;0.001). Diagnostic accuracy as quantified by the area under the receiver-operating-characteristics curve (AUC) was 0.948 (95% CI 0.938-0.958) for BNP as compared to 0.921 (95% CI 0.908-0.935) for NT-proBNP, p&amp;lt;0.001. The diagnostic superiority of BNP was consistent among predefined subgroups according to renal function and increased with the extent of renal dysfunction (Figure 1: all patients (A), patients with eGFR≥ 60 ml/min/1,73 m² (B), patients with eGFR 30-59 ml/min/1,73 m² (C), patients with eGFR &amp;lt;30ml/min/1,73 m² (D)). In contrast, prognostic accuracy for the prediction of death at 360 days was higher for NT-proBNP (AUC 0.731, 95% CI 0.702-0.760 versus 0.706, 95%CI 0.676-0.736 for BNP; p&amp;lt;0.001). The diagnostic superiority of NTproBNP was consistent among predefined subgroups according to renal function but decreased with the extent of renal dysfunction. Conclusion In patients with acute dyspnea, BNP and NT-proBNP at presentation both have very high diagnostic accuracy for AHF and moderate prognostic accuracy for death. There is a numerically small, but statistically and possibly also clinically significant diagnostic superiority of BNP and prognostic superiority of NT-proBNP.Diagnostic accuracy for AHF

Zibotentan in combination with dapagliflozin compared with dapagliflozin in patients with chronic kidney disease (ZENITH-CKD): a multicentre, randomised, active-controlled, phase 2b, clinical trial

In patients with chronic kidney disease, SGLT2 inhibitors and endothelin A receptor antagonists (ERAs) can reduce albuminuria and glomerular filtration rate (GFR) decline. We assessed the albuminuria-lowering efficacy and safety of the ERA zibotentan combined with the SGLT2 inhibitor dapagliflozin. ZENITH-CKD was a multicentre, randomised, double-blind, active-controlled clinical trial, done in 170 clinical practice sites in 18 countries. Adults (≥18 to ≤90 years) with an estimated GFR (eGFR) of 20 mL/min per 1·73 m2 or greater and a urinary albumin-to-creatinine ratio (UACR) of 150-5000 mg/g were randomly assigned (2:1:2) to 12 weeks of daily treatment with zibotentan 1·5 mg plus dapagliflozin 10 mg, zibotentan 0·25 mg plus dapagliflozin 10 mg, or dapagliflozin 10 mg plus placebo, as adjunct to angiotensin-converting enzyme inhibitors or angiotensin receptor blockers if tolerated. The primary endpoint was a change from baseline in log-transformed UACR (zibotentan 1·5 mg plus dapagliflozin vs dapagliflozin plus placebo) at week 12. Fluid retention was an event of special interest, defined as an increase in bodyweight of at least 3% (at least 2·5% must have been from total body water) from baseline or an increase of at least 100% in B-type natriuretic peptide (BNP) and either a BNP concentration greater than 200 pg/mL if without atrial fibrillation or BNP greater than 400 pg/mL if with atrial fibrillation. This trial is registered with ClinicalTrials.gov, NCT04724837, and is completed. Between April 28, 2021, and Jan 17, 2023, we assessed 1492 participants for eligibility. For the main analysis, we randomly assigned 449 (30%) participants, 447 (99%) of whom (mean age 62·8 years [SD 12·1], 138 [31%] female, 309 [69%] male, 305 [68%] White, mean eGFR 46·7 mL/min per 1·73 m2 [SD 22·4], and median UACR 565·5 mg/g [IQR 243·0-1212·6]) received treatment with zibotentan 1·5 mg plus dapagliflozin (n=179 [40%]), zibotentan 0·25 mg plus dapagliflozin (n=91 [20%]), or dapagliflozin plus placebo (n=177 [40%]). Zibotentan 1·5 mg plus dapagliflozin and zibotentan 0·25 mg plus dapagliflozin reduced UACR versus dapagliflozin plus placebo throughout the treatment period of the study. At week 12, the difference in UACR versus dapagliflozin plus placebo was -33·7% (90% CI -42·5 to -23·5; p<0·0001) for zibotentan 1·5 mg plus dapagliflozin and -27·0% (90% CI -38·4 to -13·6; p=0·0022) for zibotentan 0·25 mg plus dapagliflozin. Fluid-retention events were observed in 33 (18%) of 179 participants in the zibotentan 1·5 mg plus dapagliflozin group, eight (9%) of 91 in the zibotentan 0·25 mg plus dapagliflozin group, and 14 (8%) of 177 in the dapagliflozin plus placebo group. Zibotentan combined with dapagliflozin reduced albuminuria with an acceptable tolerability and safety profile and is an option to reduce chronic kidney disease progression in patients already receiving currently recommended therapy. AstraZeneca.

Entropy-driven reactions for controlling CRISPR/Cas12a and constructing an electrochemical biosensor for cardiac biomarkers detection.

An electrochemical biosensor is reported for controlling CRISPR/Cas12a activity through the utilization of entropy-driven reactions, alongside the construction of a highly sensitive biosensor for B-type natriuretic peptide (BNP) detection. In the biosensor, entropy-driven reactions are employed to regulate the activity of CRISPR/Cas12a-a gene editing tool-capable of nonspecific cleavage of single-stranded DNA (ssDNA). The biosensor architecture encompasses an electrode that is modified with ssDNA probes designed to hybridize with target BNP aptamers. These aptamers, furnished with labeled ssDNA triggers, facilitate the activation of CRISPR/Cas12a through interaction with its guide RNA. Upon the presence of BNP, it associates with the aptamers, subsequently liberating the triggers that instigate the entropy-driven reactions. As a consequence of these reactions, more stable duplexes emerge between the triggers and guide RNA, thereby activating CRISPR/Cas12a. The activated CRISPR/Cas12a subsequently executes cleavage of ssDNA probes residing on the electrode surface, culminating in the generation of an electrochemical signal directly (the calibration plots of differential pulse voltammetric detectionwere acquired at a working potential of 0.2V (vs. ref. electrode)) proportional to the BNP concentration. Validation of the biosensor's performance is undertaken, wherein BNP detection is demonstrated in both buffer and human serum samples. Evident in the findings is the biosensor's discernible sensitivity and specificity for BNP detection, exemplified by a detection limit of 13.53 fM and a lack of interference originating from other cardiac biomarkers, respectively. Furthermore, the biosensor's potential to discriminate between healthy individuals and those afflicted by heart failure, predicated on distinctive BNP levels, is illustrated.

A-012 Novel Method for Determining the Concentration of Total N-terminal Pro-hormone BNP (NT-proBNP) in a Sample with Mass Spectrometric Detection

Abstract Background NT-proBNP, the N-terminal fragment of the hormone B-type natriuretic peptide (BNP), is a useful clinical biomarker for diagnostic and prognostic evaluation of heart failure (HF). Recent studies show that commercially available NT-proBNP assays underestimate concentrations of NT-proBNP due to the usage of antibodies targeting the glycosylated central region of the NT-proBNP molecule. With this, a clinical need arises to establish a robust and reliable assay method which can measure the total amount of NT-proBNP, independent of the glycosylation status of the molecule. Methods To determine the concentration of NT-proBNP in patient samples, a known quantity of labelled NT-pro-BNP was added to each sample as standard. The capture of the analyte (native and standard) was performed by Dynabeads™ M-270 Epoxy beads coated with polyclonal goat antibodies, targeting non-glycosylated sites of the NT-proBNP molecule. Magnetic beads were added to the sample and incubated overnight. The isolated analytes were trypsinated directly on the beads after treatment for denaturation by unfolding and oxidation/alkylation. The reaction was stopped by addition of formic acid and the tryptic peptides were cleaned on C18 SPE columns, dried by SpeedVac and resuspended in acetonitrile for separation and analysis on LC-MS/MS (Agilent 1200 Series LC/MS system coupled to an Agilent G6490 triple quadrupole mass spectrometer). Results The Gentian LC-MS/MS validation was conducted including five studies such as Linearity, LoQ, Trueness, Precision and Carry-Over. All studies passed our defined acceptance criteria. To elucidate how glycosylation influences measurements of NT-proBNP, 81 plasma and serum samples covering a concentration range from 100 ng/L to 25 000 ng/L were measured by the Gentian LC-MS/MS method and the Roche Elecsys® proBNP I assay. Within the clinically relevant range of 100–2000 ng/L, the results between both methods exhibit a linear correlation of R2 = 0.97 and show that the commercial assay consistently underestimates the concentration of NT-proBNP by an average factor of 4.3 (3.5–5.8). Furthermore, results reveal that the concentration measurements between the commercial assay and the LC-MS/MS method converge at higher NT-proBNP concentrations. Method comparison was repeated using the Siemens ADVIA Centaur® and the Siemens IMMULITE Immunoassay systems, confirming the results of underestimation of NT-proBNP in clinically relevant areas. For method robustness investigations, the LC-MS/MS method was set up and used at two geographically different sites by different operators, using two different mass spectrometry systems (Agilent 1200 with triple quadrupole and the nano-LC-ESI-Orbitrap from Thermo Fisher Scientific), resulting in CVs from 13% to 2% for NT-proBNP concentrations ranging from 220 ng/L to 9700 ng/L. Conclusion Gentian AS presents a robust and reliable mass spectrometry method, capable of detecting the total amount of NT-proBNP in a sample, independent of its degree of glycosylation. This method is suitable for serving either as a reference method for calibrating and ensuring the accuracy of existing methods, harmonization of existing methods, or as a novel method in clinical chemistry for accurately determining the concentration of total amount of NT-proBNP.

The Effect of Omecamtiv Mecarbil in Hospitalized Patients as Compared With Outpatients With HFrEF: An Analysis of GALACTIC-HF

BackgroundIn the Global Approach to Lowering Adverse Cardiac Outcomes Through Improving Contractility in Heart Failure (GALACTIC-HF) trial, omecamtiv mecarbil, compared with placebo, reduced the risk of worsening heart failure (HF) events, or cardiovascular death in patients with HF and reduced ejection fraction. The primary aim of this prespecified analysis was to evaluate the safety and efficacy of omecamtiv mecarbil by randomization setting, that is, whether participants were enrolled as outpatients or inpatients. Methods and ResultsPatients were randomized either during a HF hospitalization or as an outpatient, within one year of a worsening HF event (hospitalization or emergency department visit). The primary outcome was a composite of worsening HF event (HF hospitalization or an urgent emergency department or clinic visit) or cardiovascular death. Of the 8232 patients analyzed, 2084 (25%) were hospitalized at randomization. Hospitalized patients had higher N-terminal prohormone of B-type natriuretic peptide concentrations, lower systolic blood pressure, reported more symptoms, and were less frequently treated with a renin–angiotensin system blocker or a beta-blocker than outpatients. The rate (per 100 person-years) of the primary outcome was higher in hospitalized patients (placebo group = 38.3/100 person-years) than in outpatients (23.1/100 person-years); adjusted hazard ratio 1.21 (95% confidence interval 1.12–1.31). The effect of omecamtiv mecarbil versus placebo on the primary outcome was similar in hospitalized patients (hazard ratio 0.89, 95% confidence interval 0.78–1.01) and outpatients (hazard ratio 0.94, 95% confidence interval 0.86–1.02) (interaction P = .51). ConclusionsHospitalized patients with HF with reduced ejection fraction had a higher rate of the primary outcome than outpatients. Omecamtiv mecarbil decreased the risk of the primary outcome both when initiated in hospitalized patients and in outpatients.

Relationship Between Results of Pathological Evaluation of Endomyocardial Biopsy and Echocardiographic Indices in Patients With Non-Ischemic Cardiomyopathy.

Background: Endomyocardial biopsy (EMB) is a useful modality in diagnosing the origin of cardiomyopathy and the condition of the impaired myocardium. However, the usefulness of obtaining an EMB from the right and left ventricles (RV and LV, respectively), and its associations with echocardiographic parameters, have not been explored. Methods and Results: Ninety-five consecutive patients with non-ischemic cardiomyopathy excluding myocarditis who underwent EMB between July 2017 and May 2019 were studied. Seventy-nine RV and 93 LV biopsy specimens were pathologically analyzed. The relationships among echocardiographic data before EMB and pathologically measured cardiomyocyte diameter (CMD) and interstitial fibrosis (IF) were evaluated. CMD in both LV and RV specimens correlated with echocardiographic LV morphology, but only CMD in the LV was significantly correlated with cardiac function evaluation, including LV ejection fraction, E' and E/E'. In contrast, there were no significant correlations between IF in either the LV or RV and any echocardiographic parameters measured. Furthermore, CMD of both ventricles was significantly correlated with B-type natriuretic peptide (BNP) concentration at EMB, whereas IF of the LV was barely related and IF of the RV was not significantly correlated with BNP concentrations. Conclusions: Pathologically evaluated CMD of EMB specimens of the LV may be more related to functional parameters for heart failure status and LV geometry on echocardiographic examination, than IF.

Association of B-Type Natriuretic Peptide Level with Clinical Outcome in Out-of-Hospital Cardiac Arrest in Emergency Department Patients.

B-type natriuretic peptide (BNP) is used for outcome assessment of various diseases. We designed this study to investigate whether BNP, which has been proven useful in the risk stratification of sudden cardiac arrest (SCA) of cardiac etiology, can also prove to be a valuable prognostic tool for SCA also included with non-cardiac etiology. In this study, we aim to investigate the relationship between measured BNP levels and clinical outcomes in SCA, regardless of the cause of SCA. This retrospective multicenter observational study was performed in two tertiary university hospitals and one general hospital between January 2015 and December 2020. The total number of SCA patients was 1625. The patients with out-of-hospital cardiac arrest over 19 years old and acquired laboratory data, including BNP at emergency department (ED) arrival, were included. BNP was measured during advanced Cardiovascular Life Support (ACLS). The exclusion criteria were age under 18 years, traumatic arrest, and without BNP. The median BNP was 171.8 (range; 5-5000) pg/mL in the return of Spontaneous Circulation (ROSC), higher than No-ROSC (p = 0.007). The median BNP concentration was 99.7 (range; 5-3040.68) pg/mL in the survival to discharge, which was significantly lower than the death group (p = 0.012). The odds ratio of survival to discharge decreased proportionally to the BNP level. The odds ratio of neurologic outcome was not correlated with the BNP level. In patients with SCA of all origins, low BNP concentration measured during ACLS correlated with an increased ratio of survival to discharge. However, BNP measured during ACLS was not found to be an independent factor.

Growth Differentiation Factor 15 and Clinical Outcomes in Japanese Patients With Heart Failure.

Heart failure (HF) is an increasing health problem associated with a high mortality rate. Growth differentiation factor (GDF) 15, a stress response cytokine belonging to the transforming growth factor-β superfamily, is associated with poor clinical outcomes in a broad spectrum of cardiovascular diseases. However, the prognostic usefulness of GDF15 in Japanese patients with HF remains unclear.Methods and Results: We measured serum concentrations of GDF15 and B-type natriuretic peptide (BNP) in 1,201 patients with HF. All patients were prospectively followed for a median period of 1,309 days. In all, 319 HF-related events and 187 all-cause deaths occurred during the follow-up period. Kaplan-Meier analysis demonstrated that, among GDF15 tertiles, the highest tertile group had the greatest risk of HF-related events and all-cause mortality. Multivariate Cox proportional hazard regression analysis demonstrated that the serum GDF15 concentration was an independent predictor of HF-related events and all-cause deaths after adjusting for confounding risk factors. Serum GDF15 improved the prediction capacity for all-cause deaths and HF-related events with a significant net reclassification index and integrated discrimination improvement. Subgroup analysis in patients with HF with preserved ejection fraction also showed the prognostic usefulness of GDF15. Serum GDF15 concentrations were associated with HF severity and clinical outcomes, indicating that GDF15 could provide additional clinical information to track the health status of patients with HF.

Initial Experience of Vericiguat Treatment in Patients with Heart Failure and Reduced Ejection Fraction.

Vericiguat, a novel oral soluble guanylate cyclase stimulator, decreased the incidence of cardiovascular death and heart failure hospitalization in the cohort receiving triple therapy for heart failure with reduced ejection fraction. However, efficacy and optimal patient selection in real-world practice in the era of "quadruple therapy" remains unknown. Consecutive patients who received vericiguat between September 2021 and December 2022 were retrospectively evaluated. A total of 28 patients (median age 66 years, median left ventricular ejection fraction 33%) were included. Of them, 21 patients (75%) received quadruple therapy, and the dose of sacubitril/valsartan was 100 mg in the median. Three patients receiving dobutamine infusion discontinued vericiguat due to symptomatic hypotension. One patient with a high N-terminal pro-B-type natriuretic peptide of 4848 pg/mL at the baseline underwent unexpected heart failure hospitalization. Efficacy was evaluated in 21 patients who continued vericiguat for more than 4 months. The plasma B-type natriuretic peptide concentration tended to increase during the six-month pre-treatment period from 104 pg/mL to 179 pg/mL on median (p = 0.665) but remained unchanged after six-month vericiguat treatment to 170 pg/mL on median (p = 0.188). Vericiguat therapy might be feasible and effective upon quadruple therapy for those with heart failure, although further investigation is warranted to validate our findings.

Cardiac imaging and biomarkers for assessing myocardial fibrosis in children with hypertrophic cardiomyopathy

Myocardial fibrosis, as diagnosed on cardiac magnetic resonance imaging (cMRI) by late gadolinium enhancement (LGE), is associated with adverse outcomes in adults with hypertrophic cardiomyopathy (HCM), but its prevalence and magnitude in children with HCM have not been established. We investigated: (1) the prevalence and extent of myocardial fibrosis as detected by LGE cMRI; (2) the agreement between echocardiographic and cMRI measurements of cardiac structure; and (3) whether serum concentrations of N-terminal pro hormone B-type natriuretic peptide (NT-proBNP) and cardiac troponin-T are associated with cMRI measurements. A cross-section of children with HCM from 9 tertiary-care pediatric heart centers in the U.S. and Canada were enrolled in this prospective NHLBI study of cardiac biomarkers in pediatric cardiomyopathy (ClinicalTrials.gov Identifier: NCT01873976). The median age of the 67 participants was 13.8 years (range 1-18 years). Core laboratories analyzed echocardiographic and cMRI measurements, and serum biomarker concentrations. In 52 children with non-obstructive HCM undergoing cMRI, overall low levels of myocardial fibrosis with LGE >2% of left ventricular (LV) mass were detected in 37 (71%) (median %LGE, 9.0%; IQR: 6.0%, 13.0%; range, 0% to 57%). Echocardiographic and cMRI measurements of LV dimensions, LV mass, and interventricular septal thickness showed good agreement using the Bland-Altman method. NT-proBNP concentrations were strongly and positively associated with LV mass and interventricular septal thickness (P < .001), but not LGE. Low levels of myocardial fibrosis are common in pediatric patients with HCM seen at referral centers. Longitudinal studies of myocardial fibrosis and serum biomarkers are warranted to determine their predictive value for adverse outcomes in pediatric patients with HCM.

Significant discordance between point of care BNP values obtained by the i-STAT and the Beckman DXI 800, causing confusion in patient management when both methods are used interchangeably by clinicians

B-type natriuretic peptide (BNP) is used as a biomarker of heart failure. In our hospital point of care (POCT) BNP test is performed in EDTA whole blood using i-STAT (Abbott Laboratories, Abbott Park, IL, USA) and in the clinical laboratory using EDTA plasma and the DXI 800 analyzer (Beckman, Brea, CA, USA). We compared BNP values in 88 patients obtained by using the i-STAT followed by using the DXI 800. The time difference between the two analyses varied from 32 min to less than 12 h. In addition, 11 specimens were simultaneously analyzed for BNP using both the i-STAT and the DXI 800 analyzer. Plotting BNP concentrations obtained by the DXI 800 in the x-axis (reference method) and the i-STAT values in the y-axis, we observed the following regression equation; y = 1.4758 x + 23.452 (n = 88, r = 0.96), indicating significant positive bias with the i-STAT. In addition, we also observed significant differences between BNP values obtained by the i-STAT and the DXI 800 in 11 specimens analyzed simultaneously. Therefore, clinicians should not use BNP concentrations obtained by the i-STAT interchangeably with BNP concentrations obtained by the DXI 800 analyzer for patient management.

Prognostic value of secretoneurin in chronic heart failure. Data from the GISSI-Heart Failure trial

BackgroundCirculating secretoneurin (SN) concentrations have been found to provide prognostic information in patients with acute heart failure. We wanted to assess whether SN would improve prognostication also in patients with chronic heart failure (HF) in a large multicenter trial. MethodsWe measured plasma SN concentrations at randomization (n = 1224) and after 3 months (n = 1103) in patients with chronic, stable HF from the GISSI-HF study. The co-primary endpoints were (1) time to death or (2) admission to hospital for cardiovascular reasons. ResultsMean age was 67 years and 80% were male. Median (quartile 1–3) SN concentrations were 42.6 (35.0–62.8) pmol/L on randomization and 42.0 (34.5–53.1) pmol/L after 3 months, which are higher than SN concentrations in healthy subjects. Higher SN concentrations at randomization were associated with lower body-mass index (BMI), lower systolic blood pressure, lower estimated glomerular filtration rate (eGFR), higher B-type natriuretic peptide (BNP) concentrations, and diagnosis of chronic obstructive pulmonary disease. During median follow-up of 3.9 years, 344 patients (27.0%) died. After adjusting for age, sex, left ventricular ejection fraction, BMI, functional class, ischemic etiology, heart rate, blood pressure, eGFR, bilirubin, comorbidities, and BNP concentrations, logarithmically transformed SN concentrations on randomization were associated with mortality (HR 2.60 (95% CI 1.01–6.70), p = 0.047). SN concentrations were also associated with admission to hospital for cardiovascular reasons, but the association was attenuated and no longer significant in multivariable analysis. ConclusionPlasma SN concentrations provided incremental prognostic information to established risk indices and biomarkers in a large cohort of chronic HF patients.