B-type Natriuretic Peptide Measurements Research Articles

B-type natriuretic peptide levels predict long-term mortality in a large cohort of adults with congenital heart disease.

Many adult patients with congenital heart disease (ACHD) are still afflicted by premature death. Previous reports suggested natriuretic peptides may identify ACHD patients with adverse outcome. The study investigated prognostic power of B-type natriuretic peptide (BNP) across the spectrum of ACHD in a large contemporary cohort. The cohort included 3392 consecutive ACHD patients under long-term follow-up at a tertiary ACHD centre between 2006 and 2019. The primary study endpoint was all-cause mortality. A total of 11 974 BNP measurements were analysed. The median BNP at baseline was 47 (24-107) ng/L. During a median follow-up of 8.6 years (29 115 patient-years), 615 (18.1%) patients died. On univariable and multivariable analysis, baseline BNP [hazard ratio (HR) 1.16, 95% confidence interval (CI) 1.15-1.18 and HR 1.13, 95% CI 1.08-1.18, respectively] and temporal changes in BNP levels (HR 1.22, 95% CI 1.19-1.26 and HR 1.19, 95% CI 1.12-1.26, respectively) were predictive of mortality (P < .001 for both) independently of congenital heart disease diagnosis, complexity, anatomic/haemodynamic features, and/or systolic systemic ventricular function. Patients within the highest quartile of baseline BNP (>107 ng/L) and those within the highest quartile of temporal BNP change (>35 ng/L) had significantly increased risk of death (HR 5.8, 95% CI 4.91-6.79, P < .001, and HR 3.6, 95% CI 2.93-4.40, P < .001, respectively). Baseline BNP and temporal BNP changes are both significantly associated with all-cause mortality in ACHD independent of congenital heart disease diagnosis, complexity, anatomic/haemodynamic features, and/or systolic systemic ventricular function. B-type natriuretic peptide levels represent an easy to obtain and inexpensive marker conveying prognostic information and should be used for the routine surveillance of patients with ACHD.

Abstract 13612: Association Between B-Type Natriuretic Peptide and Inferior Vena Cava Diameter as a Measure of Hypovolemia in Cancer Patients

Introduction: Hypovolemia is frequently seen in cancer patients due to catabolism, cachexia, and decreased oral intake. However, volume status assessment in this population is often difficult due to competing comorbid conditions such as edema. Elevated B-type natriuretic peptide (BNP) is an established biomarker of myocardial wall stress in patients with hypervolemia. We sought to determine if very low BNP could be an objective marker of hypovolemia in cancer patients Hypothesis: In cancer patients undergoing treatment, is low BNP level (&lt;10 pg/mL) associated with small inferior vena cava (IVC) diameter (&lt; 1.4 cm) - an established marker of hypovolemia on transthoracic echocardiography (TTE)?We hypothesize that BNP &lt;10 pg/mL is associated with small IVC as a marker of hypovolemia in cancer patients. Methods: We conducted a retrospective study (N=91) with solid malignancies, undergoing chemo- and/or radiation therapy (RT), divided into 3 groups based on BNP values in pg/mL: low (BNP &lt;10), normal (BNP 10-100) and high (BNP&gt;100). Retrospective data were obtained between 2016-2023 from Rush University Medical Center Cardio-Oncology Registry. IVC measurements by 2 medial trainees (Cohen’s intraclass correlation coefficient = 0.87, p &lt; 0.01) were acquired from formal TTEs obtained within 1 week of BNP measurements. Linear regression was used to calculate the adjusted means (for age, sex, BMI, blood pressure, creatinine, RT, TSH) of the 2 measured IVC diameters per datapoint. Mean difference in IVC diameters was compared between the 3 BNP groups. Results: The population mean age was 59.99 ± 12.19, 67% women. Adjusted mean IVC measurements were 1.89cm, 1.55cm, and 1.26cm for the high, normal, and low BNP groups respectively. The mean difference in IVC diameters between high and low BNP groups was 0.628 ±0.164 cm (p&lt;0.01). Conclusions: In cancer patients undergoing treatment, very low BNP (&lt;10pg/mL) was associated with small IVC as a marker of hypovolemia. In this group of patients, BNP measured with routine lab data is a readily available tool to identify individuals with hypovolemia where other measures of volume status such as physical exams might be uncertain.

Abstract 12859: Clinical Correlates and Prognostic Value of B-type Natriuretic Peptide in Left Ventricular Assist Device Recipients With Cardiogenic Shock: Insights From INTERMACS

Introduction: B-type natriuretic peptide (BNP) is a robust predictor of outcomes across the heart failure (HF) spectrum. However, data characterizing BNP levels in end-stage HF with cardiogenic shock (CS) is lacking. Furthermore, the prognostic value of BNP in left ventricular assist device (LVAD) receiving Stage D HF patients with CS has not been assessed previously. Methods: Continuous flow LVAD recipients with CS enrolled in INTERMACS between 2005 to 2017 were included. CS was defined as INTERMACS profile 1-3. The primary outcome of the study was long-term mortality. Long-term mortality was assessed in patients alive at 1-month post-surgery. Secondary outcomes included peri-operative mortality (&lt;30 days of surgery), cardiovascular mortality, arrhythmia, and right HF. The cohort was stratified by quartiles of BNP levels. Multivariable Cox proportional hazard models, adjusted for age, sex, body mass index, INTERMACS profile, center volume, implantation year, device strategy, estimated glomerular filtration rate, employment status, and education level, were used to assess the association between BNP levels and outcomes. Results: Among 7,290 LVAD recipients with CS, the median pre-implantation BNP value was 859 (427, 1,614) pg/mL. Males [851(429, 1,557) pg/mL, P =0.07], non-Hispanic Blacks [777 (362, 1,514) pg/mL, P =&lt;0.001], and obese [642 (311, 1,170) pg/mL, P =&lt;0.001] patients had lower BNP values. Over a median follow-up of 14.7 (6.9, 28.7) months, the risk of long-term mortality was similar in the second [HR adj :1.06 (0.94-1.20)], third [HR adj :0.97 (0.85-1.10)], and fourth [HR adj :1.04 (0.91-1.18)] quartiles of BNP compared with the first quartile of BNP. Similarly, the risk of peri-operative mortality, cardiovascular mortality, arrhythmia, and right HF did not vary by the quartiles of BNP. Conclusions: BNP has poor prognostic value in LVAD recipients with CS and the value of routine measurement of BNP in this population needs further investigation.

Cardiac Amyloid Detection by PET/CT Imaging of Iodine (124I) Evuzamitide (124I-p5+14): A Phase 1/2 Study

BackgroundThe noninvasive detection of cardiac amyloid, as well as deposits in other vital organs, is critical for early diagnosis and quantitative disease monitoring. Positron emission tomography is an intrinsically quantitative imaging modality suitable for high-resolution amyloid detection. ObjectivesThis study sought to evaluate the safety and efficacy of a novel amyloid-reactive peptide, designated p5+14, labeled with iodine-124 (124I), in patients with diverse types of systemic amyloidosis. MethodsIn a single-site, open label phase 1/2 study (NCT03678259), the safety, biodistribution, and sensitivity of a single intravenous infusion of 124I-evuzamitide was assessed in patients with systemic amyloidosis (n = 50), asymptomatic transthyretin sequence variant carriers (n = 2), and healthy volunteers (n = 5). Subjects were administered 1.4 ± 0.2 mg of 124I-evuzamitide (71.5 ± 12.4 MBq) and positron emission tomography/x-ray computed tomography images acquired at 5.2 hours (Q25-Q75: 4.9-5.4 hours) postinfusion. Images were assessed visually and semi-quantitatively for positive uptake of radiotracer in the heart and other major organs. ResultsUptake of 124I-evuzamitide in the heart and other abdominothoracic organs was consistent with the patient’s clinical presentation and the type of amyloidosis. The patient- and cardiac-associated sensitivity for imaging and clinical observations was 93.6% (95% CI: 82.8%-97.8%) and 96.2% (95% CI: 81.8%-99.8%), respectively. Semi-quantitative uptake of the radiotracer correlated significantly with serum N-terminal pro–B-type natriuretic peptide measurements in patients with light chain–associated amyloidosis. Cardiac uptake was not observed in any healthy volunteers. The agent was well tolerated, with 1 drug-related adverse event and no deaths. Conclusions124I-evuzamitide is an amyloid-binding radiotracer capable of detecting cardiac amyloid in patients with high sensitivity.

Advantages of Electro-deposited Gold on Carbon Electrodes for NT-proBNP Immunosensor for Development of Heart Failure Test Kit

Accurate measurement of the N-terminal pro B-type natriuretic peptide (NT-proBNP) in serum is important for the diagnosis of heart failure (HF). Carbon screen-printed electrodes (SPCEs) modified with graphene oxide (GO) or gold (Au) were compared for the construction of NT-proBNP immunosensors. NT-proBNP and its recognition unit, a single-chain variable fragment fused with alkaline phosphatase (scFv-AP), were expressed and purified. The currents of the electrodes immobilized with scFv-AP were measured after adding an ethanolamine (ETA), blank and NT-proBNP in either phosphate buffer saline (PBS) or human serum. SPCE/Au had lower mean baseline slopes than for SPCE/GO for all measurements, in both PBS and serum, indicating greater accuracy for SPCE/Au. None of the measurements in PBS had statistically different peak currents between SPCE/GO and SPCE/Au; however, there was a significant difference with the serum. The significant reduction of SPCE/GO peak currents after applying serum blank implied non-specific absorption on the surface. The peak current of 300 pg/mL of NT-proBNP in the serum measured on SPCE/Au was significantly higher (by a factor of three) than on SPCE/GO, suggesting the possibility of using SPCE/Au to detect NT-proBNP at higher concentrations. The binding efficiency of scFv-AP to NT-proBNP did not depend on the electrodes, as shown by the similar delta peak-currents (Blank-Target). Thus, immobilized scFv-AP on SPCE/Au electrodes had good potential to accurately detect NT-proBNP in serum, for use in the fabrication of an HF test kit.

Association of Longitudinal B-Type Natriuretic Peptide Monitoring With Kidney Failure in Patients With CKD: A Cohort Study

Both hypervolemia and hypovolemia are associated with chronic kidney disease (CKD) progression. Although longitudinal monitoring of B-type natriuretic peptide (BNP) may aid physicians' decision making about the optimization of volume status, its clinical benefit remains uncertain in CKD. This study assessed the association between BNP monitoring and the risk of incident kidney replacement therapy (KRT). Retrospective cohort study. A total of 2,998 outpatients with stages 3-5 of nondialyzed CKD referred to the department of nephrology at an academic hospital. BNP monitoring. KRT, acute kidney injury (AKI), and heart failure hospitalization. Marginal structural models, which create a balanced pseudo population at each time point, were applied to account for potential time-dependent confounders. Inverse probability weighted pooled logistic regression models were employed to estimate hazard ratios. At baseline, the median age and estimated glomerular filtration rate were 66 years and 38.1mL/min/1.73m2, respectively. During the follow-up period (median, 5.9 [IQR, 2.8-9.9] years), 449 patients required KRT, 765 had AKI, and 236 were hospitalized for heart failure. After adjustment for time-updated clinical characteristics and physician-specific practice styles, BNP monitoring was associated with lower risks of KRT (HR, 0.44 [95% CI, 0.21-0.92]), AKI (HR, 0.36 [95% CI, 0.18-0.72]), and heart failure hospitalization (HR, 0.37 [95% CI, 0.14-0.95]). The association between BNP monitoring and KRT was attenuated after additional adjustment for AKI or heart failure hospitalization as a time-varying covariate. Residual confounding by measured and unmeasured variables or indications for BNP measurements. BNP monitoring was associated with a lower risk of KRT among patients with CKD that did not require dialysis. This association is potentially mediated through a reduced risk of AKI or heart failure hospitalization. Both volume overload and volume depletion are deleterious to kidney function. B-type natriuretic peptide (BNP) is a biomarker that reflects volume status not only in heart failure but also in nondialysis chronic kidney disease (CKD). Although longitudinal BNP monitoring may aid physicians' decision making about the optimization of volume status, its clinical benefit remains uncertain in CKD. In this cohort study analyzing 2,998 patients with nondialyzed CKD, BNP monitoring was associated with a lower risk of kidney replacement therapy, acute kidney injury, and heart failure hospitalization over the follow-up period. The association with kidney replacement therapy may be mediated through a reduced risk of acute kidney injury or heart failure hospitalization. BNP monitoring may aid physicians in optimal fluid management, potentially conferring better kidney outcomes.

Racial differences in low natriuretic peptide levels: Implications for heart failure clinical trials

Some patients with heart failure (HF) have low natriuretic peptide (NP) levels. It is unclear whether specific populations are disproportionately excluded from participation in randomized clinical trials (RCT) with inclusion requirements for elevated NPs. We investigated factors associated with unexpectedly low NP levels in a cohort of patients hospitalized with HF, and the implications on racial diversity in a prototype HF RCT. We created a retrospective cohort of 31,704 patients (age 72 ± 16 years, 49% female, 52% Black) hospitalized with HF from 2010 to 2020 with B-type natriuretic peptide (BNP) measurements. Factors associated with unexpectedly low BNP levels (<50 pg/mL) were identified using multivariable logistic regression models. We simulated patient eligibility for a prototype HF trial using specific inclusion and exclusion criteria, and varying BNP cut-offs. Unexpectedly low BNP levels were observed in 8.9% of the cohort. Factors associated with unexpectedly low BNP levels included HFpEF (aOR 3.76, 95% CI: 3.36, 4.20), obesity (aOR 1.96, 95% CI: 1.73, 2.21), self-identification as Black (aOR 1.53, 95% CI: 1.36, 1.71), and male gender (aOR 1.45, 95% CI: 1.31, 1.60). Applying limited clinical inclusion and exclusion criteria from PARAGLIDE-HF disproportionately excluded Black patients, with impairment in renal function having the greatest impact. Adding thresholds for BNP of ≥35, ≥50, ≥67, ≥100, and ≥150 pg/mL demonstrated the risk of exclusion was higher for Black compared to non-Black patients (RR=2.03 [95% CI: 1.73, 2.39], 1.90 [95% CI: 1.68, 2.15], 1.63 [95% CI: 1.48, 1.81], 1.38 [95% CI: 1.28, 1.50], and 1.23 [95% CI: 1.15, 1.31], respectively). Nearly 10% of patients hospitalized with HF have unexpectedly low BNP levels. Simulating inclusion into a prototype HFpEF RCT demonstrated that requiring increasingly elevated NP levels disproportionately excludes Black patients.

Comprehensive Cardiovascular Magnetic Resonance Tissue Characterization and Cardiotoxicity in Women With Breast Cancer

There is a growing interest in understanding whether cardiovascular magnetic resonance (CMR) myocardial tissue characterization helps identify risk of cancer therapy-related cardiac dysfunction (CTRCD). To describe changes in CMR tissue biomarkers during breast cancer therapy and their association with CTRCD. This was a prospective, multicenter, cohort study of women with ERBB2 (formerly HER2)-positive breast cancer (stages I-III) who were scheduled to receive anthracycline and trastuzumab therapy with/without adjuvant radiotherapy and surgery. From November 7, 2013, to January 16, 2019, participants were recruited from 3 University of Toronto-affiliated hospitals. Data were analyzed from July 2021 to June 2022. Sequential therapy with anthracyclines, trastuzumab, and radiation. CMR, high-sensitivity cardiac troponin I (hs-cTnI), and B-type natriuretic peptide (BNP) measurements were performed before anthracycline treatment, after anthracycline and before trastuzumab treatment, and at 3-month intervals during trastuzumab therapy. CMR included left ventricular (LV) volumes, LV ejection fraction (EF), myocardial strain, early gadolinium enhancement imaging to assess hyperemia (inflammation marker), native/postcontrast T1 mapping (with extracellular volume fraction [ECV]) to assess edema and/or fibrosis, T2 mapping to assess edema, and late gadolinium enhancement (LGE) to assess replacement fibrosis. CTRCD was defined using the Cardiac Review and Evaluation Committee criteria. Fixed-effects models or generalized estimating equations were used in analyses. Of 136 women (mean [SD] age, 51.1 [9.2] years) recruited from 2013 to 2019, 37 (27%) developed CTRCD. Compared with baseline, tissue biomarkers of myocardial hyperemia and edema peaked after anthracycline therapy or 3 months after trastuzumab initiation as demonstrated by an increase in mean (SD) relative myocardial enhancement (baseline, 46.3% [16.8%] to peak, 56.2% [18.6%]), native T1 (1012 [26] milliseconds to 1035 [28] milliseconds), T2 (51.4 [2.2] milliseconds to 52.6 [2.2] milliseconds), and ECV (25.2% [2.4%] to 26.8% [2.7%]), with P <.001 for the entire follow-up. The observed values were mostly within the normal range, and the changes were small and recovered during follow-up. No new replacement fibrosis developed. Increase in T1, T2, and/or ECV was associated with increased ventricular volumes and BNP but not hs-cTnI level. None of the CMR tissue biomarkers were associated with changes in LVEF or myocardial strain. Change in ECV was associated with concurrent and subsequent CTRCD, but there was significant overlap between patients with and without CTRCD. In women with ERBB2-positive breast cancer receiving sequential anthracycline and trastuzumab therapy, CMR tissue biomarkers suggest inflammation and edema peaking early during therapy and were associated with ventricular remodeling and BNP elevation. However, the increases in CMR biomarkers were transient, were not associated with LVEF or myocardial strain, and were not useful in identifying traditional CTRCD risk.

Exercise Capacity, NT-proBNP, and Exercise Hemodynamics in Adults Post-Fontan

BackgroundCardiopulmonary exercise testing (CPET) and N-terminal pro–B-type natriuretic peptide (NT-proBNP) measurement are frequently performed in adults post-Fontan, but their correlations with exercise invasive hemodynamics are poorly understood. Moreover, whether exercise cardiac catheterization provides incremental prognostic information is unknown. ObjectivesThe authors sought to correlate resting and exercise Fontan pressures (FP) and pulmonary artery wedge pressure (PAWP) with peak oxygen consumption (VO2) on CPET, NT-proBNP, and clinical outcomes. MethodsThis was a retrospective cohort of 50 adults (age ≥18 years) post-Fontan undergoing supine exercise venous catheterization between 2018 and 2022. ResultsMedian age was 31.5 years (IQR: 23.7-36.5 years). Ventricular ejection fraction was 48.5% ± 13.0%. Exercise FP and PAWP were related to peak VO2 and ln NT-proBNP levels. Patients with peak VO2 <50% predicted had higher exercise FP (30.0 ± 6.8 mm Hg vs 19 mm Hg [IQR: 16-24 mm Hg]; P < 0.001) and PAWP (25.9 ± 6.3 mm Hg vs 15.1 ± 7.0 mm Hg; P <0.001) compared with those with more preserved exercise capacity. Exercise FP (30.0 ± 7.1 mm Hg vs 23.2 ± 7.2 mm Hg; P = 0.003) and PAWP (25.1 ± 6.7 mm Hg vs 18.8 ± 7.9 mm Hg; P = 0.006) were higher in those with NT-proBNP levels ≥300 pg/mL. During a follow-up of 0.9 years (IQR: 0.6-2.9 years), exercise FP and PAWP remained independently associated with a composite of death, cardiac transplantation, or hospitalization due to heart failure/refractory arrhythmias after adjusting for confounders. ConclusionsIn adults post-Fontan, resting and exercise FP and PAWP were inversely related to exercise capacity on noninvasive CPET, and exercise hemodynamics were directly related to NT-proBNP levels. Exercise FP and PAWP were independently associated with clinical outcomes and might be more sensitive than resting values to predict clinical outcomes.

EDTA plasma in glass and PET tubes is suitable for measurement of B-type natriuretic peptide on the Mindray CL-6000i.

To explore differences in BNP concentration and stability and evaluate BNP accuracy in different collection tubes. BNP concentrations in heparin/glass, EDTA/glass, and EDTA/ PET tubes were measured on the Mindray CL-6000i at 0.5, 1, 2, and 4 h after collection. Differences were evaluated using Wilcoxon's paired tests and Bland-Altman plots. BNP stability and measurement accuracies were estimated using Kruskal-Wallis H tests and recovery tests. BNP concentrations in EDTA/glass tubes were 31.4% higher than those in heparin/glass tubes and 3.04% lower than those in EDTA/PET tubes. BNP stability significantly decreased in the heparin/glass tube. BNP remained stable in EDTA/glass and EDTA/PET tubes at room temperature for 4 h. BNP recovery rates in heparin/glass, EDTA/glass, and EDTA/PET tubes were 77.46, 86.04, and 88.23%, respectively. Plasma in EDTA/glass and EDTA/PET tubes is suitable for BNP measurement on the Mindray CL-6000i.

Elevated B-type natriuretic peptide level expression associated with acute myocardial infarction patients in Jammu population (India)

B-type natriuretic peptide (BNP) is a highly sensitive and specific indicator of the size of myocardial infarction, which can help in assessing the degree of cardiovascular risk. Elevated BNP levels in patients hospitalized for acute myocardial infarction (AMI) are associated with heart failure and mortality, and the measurements of BNP in a short-term period could be helpful to predict the future events. The role of short-term follow-up BNP level has not been established in the patients with AMI. This retrospective study was conducted on the patients admitted to the Government Medical College, Jammu (India). The analysis of blood EDTA sample was analysed for BNP and this test was performed by using a fully automated random access immunoassay analyser whose principle is based on micro-particle enzyme immunoassay (MEIA). The reference range of BNP is 0-100 pg mL-1. The study revealed a 90% BNP increase in AMI patients in comparison to the 10% increase in normal healthy ones. However, BNP showed elevated levels in healthy individuals suffering from renal insufficiency. The BNP was > 100 pg mL-1 in the majority of AMI patients while in controls BNP is <100 pg mL-1.

NT-proBNP increase during stress echocardiography predicts significant changes in ischemic mitral regurgitation severity in patients qualified for surgical revascularization.

In many patients, significant changes in ischemic mitral regurgitation (IMR) severity during exercise can be observed independent of the degree of IMR at rest. This study aimed to investigate the correlations between N-terminal fragment B-type natriuretic peptide (NT-proBNP) and echocardiography measurements at rest and at peak exercise in patients with moderate IMR who qualified for surgical revascularization. A total of 100 patients eligible for coronary artery bypass grafting, were included in this prospective study. All patients underwent exercise echocardiography. Additionally, the levels of NT-proBNP were measured at rest and after peak exercise. A positive correlation of absolute NT-proBNP levels with effective regurgitant orifice area (EROA) were observed and with tricuspid regurgitant peak gradient (TRPG) at peak exercise. Absolute ΔNT-proBNP during exercise and the tenting area at rest were independent predictors of severe IMR at peak exercise. The level of absolute ΔNT-proBNP during exercise and coaptation height at rest were the most important predictors of significant increases in TRPG. The best cutoff value for ΔNT-proBNP as a predictor for increases in EROA at peak exercise was 68.9 pg/mL and to predict an increase in TRPG ≥ 50 mmHg at peak exercise was 68 pg/mL. The level of ΔNT-proBNP during exercise was the most important parameter in predicting significant changes in IMR severity and pulmonary pressure. Based on the present data, it can be speculated that integration of the assessment of NT-proBNP at rest and at exercise might improve patient selection for valve surgery.

Clinical Presentation of Myocarditis in Children Visiting Dr Ruth KM PFAU, Civil Hospital, Karachi. A Cross-Sectional Study

Objective: To determine the frequency of various clinical presentations of myocarditis in children visiting to Dr Ruth KM PFAU, Civil Hospital Karachi. Study design: Cross-Sectional Study. Place and duration: Department of Pediatric Medicine, Dr Ruth K.M PFAU Civil Hospital, Karachi, Pakistan from September, 2020, to March, 2021 Methodology: The study covered all patients who visited Karachi's Civil Hospital and met the inclusion criteria. After describing the study's process, hazards, and benefits, informed consent was obtained. The initial ECG, echocardiography, and cardiac enzyme readings were all documented. Stroke, congenital heart disease, sepsis, asthma, pulmonary embolism, cardiomyopathy, gastroenteritis, diabetes mellitus, and renal failure were among the clinical presentations that were noted. The proforma that is supplied at the end was filled out with all the acquired data and used electronically for research. Results: Age was 6.8± 2.1 years on average. A total of 238 (67.6%) of the 352 patients were male, and 114 (32.4%) were female. In patients with myocarditis who presented clinically, renal disease was found in 46 (13.1%), cardiomyopathy in 30, congenital heart disease in 56 (15.9%), stroke in 41 (11.5%), gastroenteritis in 65 (18.5%), diabetes mellitus in 19 (5.4%), sepsis in 32 (9.2%), and asthma in 48 (13.6%) patients, while pulmonary embolism was found in 15 (4.3%) patients. Practical implication There is growing evidence to support the use of tests such as cardiac magnetic resonance imaging and serum N-terminal B-type natriuretic peptide measurements as supplements to clinical diagnosis. These could eventually lessen the need for invasive procedures like endomyocardial biopsy, which is still the gold standard. Conclusion: The most frequent clinical manifestation of myocarditis was gastroenteritis, which was followed by congenital heart disease and asthma. For the purpose of validating the results so far, additional extensive research is advised. Keywords: Clinical Presentation, Myocarditis, Epidemiology, Asthma, Gastroenteritis

B‐Type Natriuretic Peptide and Long‐Term Cardiovascular Mortality in Patients With Coronary Heart Disease

BackgroundThe plasma concentration of B‐type natriuretic peptide (BNP) is a strong predictor of adverse cardiovascular events. The aim of this study was to determine whether the association between plasma BNP concentration and cardiovascular mortality is sustained or diminishes with increasing time after BNP is measured.Methods and ResultsSix thousand seven hundred forty patients with a history of myocardial infarction or unstable angina who participated in the LIPID (Long‐Term Intervention with Pravastatin in Ischemic Disease) trial had plasma BNP concentration measured at baseline and after 1 year. Associations with cardiovascular mortality were evaluated in landmark analyses 1 to <5, 5 to <10, and 10 to 16 years after randomization. There were 1640 cardiovascular deaths. The cardiovascular mortality rate increased progressively from 10.2 to 19.1 to 26.3/1000 patient‐years from 1 to <5, 5 to <10, and 10 to 16 years after baseline, respectively. The average of baseline and 1‐year BNP concentration was more strongly associated with cardiovascular mortality compared with baseline or 1‐year BNP only. The hazard ratio (HR) for cardiovascular death associated with each doubling of average BNP concentration was similar during years 1 to <5 (HR, 1.53 [95% CI, 1.44–1.63]), years 5 to <10 (HR, 1.52 [95% CI, 1.44–1.60]), and years 10–16 (HR, 1.43 [95% CI, 1.36–1.50]), P<0.0001 for all.ConclusionsBNP concentration remains an independent predictor of cardiovascular mortality more than a decade after it is measured. Because of random variation in plasma concentrations, the average of >1 BNP measurement improves long‐term risk prediction.

Mechanistic insights into chloride-related heart failure progression according to the plasma volume status.

AimsTwo types of heart failure (HF) progression were recently proposed on the basis of an increased vs. non‐increased serum chloride concentration. The applicability of this concept to real‐world HF pathophysiology requires further investigation. The present study evaluated the mechanisms of HF progression to a different type according to changes in the estimated plasma volume status (ePVS).Methods and resultsData from 47 patients (32% men; 78.2 ± 9.7 years of age) with stable to worsening HF (37.5 ± 16 days) were analysed. Physical examination, standard blood tests, and b‐type natriuretic peptide (BNP) measurements were conducted. The ePVS was calculated as follows: ePVS (dL/g) = [100 − haematocrit (%)]/[haemoglobin (g/dL)]. For the study subjects as a whole (n = 47), changes in the ePVS correlated positively with changes in the serum chloride concentration from stable to worsening HF (r = 0.398, P = 0.0056). When divided into two groups of worsening HF with an increased (n = 31) vs. non‐increased serum chloride concentration (n = 16), no significant baseline differences in body weight, serum logBNP, or ePVS were detected between groups. Under worsening HF, the increase in body weight (2.34 ± 1.12 vs. 2.59 ± 1.56 kg, P = 0.57) and logBNP (0.39 ± 0.30 vs. 0.54 ± 0.31 pg/mL, P = 0.13) did not differ between groups, but the increase in the ePVS was smaller in the group with a non‐increased serum chloride concentration compared with that with an increased serum chloride concentration (0.292 ± 0.49 vs. 0.653 ± 0.60 dL/g, P = 0.044). An increase in the %change in ePVS ≥ 10% was less common in patients with a non‐increased chloride concentration (37% vs. 71%, P = 0.03). Patients with a non‐increased serum chloride concentration had more HF signs (3.31 ± 0.79 vs. 2.65 ± 0.71, P = 0.005) and a higher incidence of pulmonary rales (63% vs. 16%, P = 0.0024) than those with an increased serum chloride concentration.ConclusionsAccording to the changes in the ePVS, HF progression may result from a difference between two HF types (i.e. increased vs. non‐increased serum chloride concentration) in the cardiac reserve in response to a given cardiac burden by modulating plasma volume status via the possible tonicity potential of chloride.

Serial measurement of B-type natriuretic peptide and future cardiovascular events in patients with type 2 diabetes mellitus without known cardiovascular disease

BackgroundIn patients with type 2 diabetes mellitus (T2DM) without known cardiovascular disease, the association between B-type natriuretic peptide (BNP) and cardiovascular events except for heart failure has not been elucidated. We aimed to investigate this association in high-risk T2DM patients. MethodsWe analyzed the association between BNP and cardiovascular events, including coronary, cerebral, renal, and vascular events or cardiovascular death based on the single and serial measurement of BNP in T2DM patients with retinopathy and hyperlipidemia without known cardiovascular disease enrolled in the EMPATHY study. ResultsData from 4966 patients were analyzed for baseline BNP analysis. The median BNP value was 15.0 pg/mL. When analyzed in quartiles of baseline BNP (interquartile range 7.5–29.2 pg/mL), Q2, Q3, and Q4 were associated with cardiovascular events compared with Q1 (hazard ratio [HR]: Q2, 1.91 [P = 0.003]; Q3, 1.63 [P = 0.031]; Q4, 3.20 [P < 0.001]). The analysis of 12-month BNP showed similar associations. In serial BNP measurement, compared with low–low BNP group (baseline ≤35 pg/mL and 12-month ≤35 pg/mL), low–high BNP group as well as high–high BNP group was associated with cardiovascular events (HR: low–high, 2.05 [P = 0.004]; high–high, 2.07 [P = 0.001]) and non-renal cardiovascular events. High–low BNP group tended to be associated with non-renal cardiovascular events (HR vs low–low: 2.05 [P = 0.056]). ConclusionsBNP levels were associated with first cardiovascular events except for heart failure in T2DM patients with retinopathy and hyperlipidemia. Serial BNP measurement may be useful in further stratifying high-risk patients among this T2DM population.

Clinical Practice Guidelines for diagnosis of organic involvement of amyloidosis: Part 2/3.Year 2020

Use the PICO format to generate a series of questions, focusing on the specificity and sensitivity of the amyloidosis diagnostic test. PubMed searches were conducted in English and Spanish from July to August 2019. The level of evidence and recommendation are based on the GRADE system (http://www.gradeworkinggroup.org/index.htm). The recommendations are graded according to their direction (for or against) and strength (strong and weak). Finally, it is recommended to use GLIA tools to evaluate the obstacles and facilitators in implementation. A strong suggestion indicates a high degree of trust in support or opposition to the intervention. When defining a strong recommendation, this guide uses the "recommended" language. The weaker recommendations indicate that the outcome of the intervention (favorable or unfavorable) is doubtful. In this case, if a weak recommendation is defined, the "recommendation" language is used. Recommendations must be explained within the scope of special care in validated diagnostic studies conducted by specially trained doctors. Presumably, the attending physician has a high degree of suspicion of amyloidosis. It assumes that diagnostic research is conducted by well-trained doctors using a validated standardized method. This guide is intended for health care professionals and those involved in health care policies to help ensure that the necessary agreements have been reached to provide appropriate care. For patients with suspected amyloidosis, it is recommended: Electrocardiogram be used as a preliminary assessment for all patients with amyloidosis. Doppler echocardiography conventional be used as the initial image of the first choice for cardiac amyloidosis in patients diagnosed with suspected heart involvement due to amyloidosis. Echocardiographic strain diagnosis for patients with amyloidosis prompted by conventional echocardiography or uncertain. Cardiac magnetic resonance imaging (MRI) be used for the diagnosis of cardiac amyloidosis in patients with previous studies suggesting or uncertain amyloidosis. T1 mapping technology for cardiac MRI to diagnose myocardial amyloidosis as an alternative to MRI, for patients with kidney failure or contraindication to other studies Cardiac MRI examination with T1 localization technique for patients who have previously studied amyloidosis, and measure the extracellular volume and quantify the degree of cardiac involvement in order to diagnose and measure the cardiac involvement caused by amyloidosis. Cardiac MRI with T1 mapping technique and extracellular volume measurement for the early diagnosis of amyloidosis in patients with previous studies suggestive of amyloidosis. Measurement of type B-type natriuretic peptide measurement be used for screening and diagnosis of cardiac amyloidosis. Pyrophosphate scintigraphy to make a preliminary diagnosis of patients with suspected cardiac amyloidosis, so as to distinguish ATTR (positive) from other patients.

Prognostic significance of different congestion evaluation modalities in acute heart failure patients classified according to left ventricular ejection fraction

Abstract Background Congestion is the main reason for hospital admission in patients with acute heart failure (AHF). Lung ultrasound (LUS) examination has been proposed as a simple, accurate, and available tool to assess pulmonary congestion, adding significant prognostic insights to clinical examination. Aim This is a multicentre retrospective study aiming to investigate the prognostic value accuracy of B-lines, compared with B-type natriuretic peptide (BNP) and clinical congestion both at admission and at discharge in a large cohort of patients admitted for AHF divided according to ejection fraction cut-off in HFrEF, HFmrEF and HFpEF). Methods We analysed the merged data of four cohorts hospitalized for AHF. All patients underwent clinical assessment, echocardiography evaluation, BNP measurement and LUS measurements in 8 or 28 chest zones. The primary outcome was the composite endpoint of all-cause mortality and/or HF re-hospitalization at 60 and 180 days. Results A total of 551 patients (264HFrEF, 100 HFmrEF and 187 HFpEF) were included. Median age was 77 [69–82] and 337 patients were men. Dividing our population according to HF classifications, we found that admission BNP levels were significantly higher in HFrEF compared to HFmrEF and HFpEF (p=0.002). No significant differences in terms of admission B-lines count were found among groups (p=0.80). ROC Curve analysis showed the significant prognostic power (p&amp;lt;0.05) of clinical congestion score, BNP and B-lines at admission. These findings were confirmed also for the same variables at discharge (p&amp;lt;0.05). Univariate analysis confirmed as predictor of poor prognosis admission congestion score≥2 (HR: 4.12 [2.84–5.99]; p&amp;lt;0.001), admission B-lines&amp;gt;30 (HR: 1.43 [1.02–1.99]; p=0.035), tricuspid anular plane systolic excursion (TAPSE) ≤16 mm (HR: 1.74 [1.25–2.42]; p=0.001), inferior cave vein (ICV) &amp;gt;21 mm (HR: 2.74 [1.80–4.18]; p&amp;lt;0.001) and E/e' ≥15 (HR: 1.71 [1.18–2.47]; p=0.005). Multivariable analysis demonstrated that admission B-lines were significantly related to poor prognosis only in HFrEF (p=0.025) and HFpEF (p=0.041), but not in HFmrEF (p=0.59). Considering the change from admission to discharge of congestion score, BNP and B-lines, the Δ B-lines during hospitalization remains the only significant predictor of poor prognosis (≥60days) across HF spectrum (HFrEF, HFmrEF and HFpEF; p≤0.001). Conclusions Although both clinical congestion signs and B-lines were predictors of all-cause mortality and HF rehospitalization at 180 days, the changes of these variables during hospitalization were the stronger predictor of poor outcome. In particular, an inadequate B-lines in-hospital reduction (Δ B-lines &amp;lt;9), was significant associated to increased risk for adverse event in all HF subtypes. Current study confirm the relevance to apply a multiparametric congestion assessment in order to better stratify hospitalized AHF patients. Funding Acknowledgement Type of funding sources: None.

NT-proBNP/BNP ratio for prognostication in European Caucasian patients enrolled in a heart failure prevention programme.

AimsGuidelines support the role of B‐type natriuretic peptide (BNP) and amino‐terminal pro‐BNP (NT‐proBNP) for risk stratification of patients in programmes to prevent heart failure (HF). Although biologically formed in a 1:1 ratio, the ratio of NT‐proBNP to BNP exhibits wide inter‐individual variability. A report on an Asian population suggests that molar NT‐proBNP/BNP ratio is associated with incident HF. This study aims to determine whether routine, simultaneous evaluation of both BNP and NT‐proBNP is warranted in a European, Caucasian population.Methods and ResultsWe determined BNP and NT‐proBNP levels for 782 Stage A/B HF patients in the STOP‐HF programme. The clinical, echocardiographic, and biochemical associates of molar NT‐proBNP/BNP ratio were analysed. The primary endpoint was the adjusted association of baseline molar NT‐proBNP/BNP ratio with new‐onset HF and/or progression of left ventricular dysfunction (LVD). We estimated the C‐statistic, integrated discrimination improvement, and the category‐free net reclassification improvement metric for the addition of molar NT‐proBNP/BNP ratio to adjusted models. The median age was 66.6 years [interquartile range (IQR) 59.5–73.1], 371 (47.4%) were female, and median molar NT‐proBNP/BNP ratio was 1.91 (IQR 1.37–2.93). Estimated glomerular filtration rate, systolic blood pressure, left ventricular mass index, and heart rate were associated with NT‐proBNP/BNP ratio in a linear regression model (all P < 0.05). Over a median follow‐up period of 5 years (IQR 3.4–6.8), 247 (31.5%) patients developed HF or progression of LVD. Log‐transformed NT‐proBNP/BNP ratio is inversely associated with HF and LVD risk when adjusted for age, gender, diabetes, hypertension, vascular disease, obesity, heart rate, number of years of follow‐up, estimated glomerular filtration rate, and baseline NT‐proBNP (odds ratio 0.71, 95% confidence interval 0.55–0.91; P = 0.008). However, molar NT‐proBNP/BNP ratio did not increase the C‐statistic (Δ −0.01) and net reclassification improvement (0.0035) for prediction of HF and LVD compared with NT‐proBNP or BNP alone. Substitution of NT‐proBNP for BNP in the multivariable model eliminated the association with HF and LVD risk.ConclusionsThis study characterized, for the first time in a Caucasian Stage A/B HF population, the relationship between NT‐proBNP/BNP ratio and biological factors and demonstrated an inverse relationship with the future development of HF and LVD. However, this study does not support routine simultaneous BNP and NT‐proBNP measurement in HF prevention programmes amongst European, Caucasian patients.

Relationship of ejection fraction and natriuretic peptide trajectories in heart failure with baseline reduced and mid-range ejection fraction

BackgroundThe prognostic importance of trajectories of neurohormones relative to left ventricular function over time in heart failure with reduced and mid-range EF (HFrEF and HFmrEF) is poorly defined. ObjectiveTo evaluate left ventricular ejection fraction (LVEF) and B-type natriuretic peptide (BNP) trajectories in HFrEF and HFmrEF. MethodsAnalyses of LVEF and BNP trajectories after incident HF admissions presenting with abnormal LV systolic function were performed using 3 methods: a Cox proportional hazards model with time-varying covariates, a dual longitudinal-survival model with shared random effects, and an unsupervised analysis to capture 3 discrete trajectories for each parameter. ResultsAmong 1,158 patients (68.9 ± 13.0 years, 53.3% female), both time-varying LVEF measurements (P=.001) and log-transformed BNP measurements (p-values=2 × 10−16) were independently associated with survival during 6 years after covariate adjustment. In the dual longitudinal/survival model, both LVEF and BNP trajectories again were independently associated with survival (P<.0001 in each model); however, LVEF was more dynamic than BNP (P <.0001 for time covariate in LVEF longitudinal model versus P=.88 for the time covariate in BNP longitudinal model). In the unsupervised analysis, 3 discrete LVEF trajectories (dividing the cohort into approximately thirds) and 3 discrete BNP trajectories were identified. Discrete LVEF and BNP trajectories had independent prognostic value in Kaplan-Meier analyses (P<.0001), and substantial membership variability across BNP and LVEF trajectories was noted. ConclusionAlthough LVEF trajectories have greater temporal variation, BNP trajectories provide additive prognostication and an even stronger association with survival times in heart failure patients with abnormal LV systolic function.