Plasma Brain Natriuretic Peptide Research Articles

ASA Status, NPPA/NPPB Haplotype and Coronary Artery Disease Have an Impact on BNP/NT-proBNP Plasma Levels.

Plasma concentrations of natriuretic peptides (NP) contribute to risk stratification and management of patients undergoing non-cardiac surgery. However, genetically determined variability in the levels of these biomarkers has been described previously. In the perioperative setting, genetic contribution to NP plasma level variability has not yet been determined. A cohort of 427 patients presenting for non-cardiac surgery was genotyped for single-nucleotide polymorphisms (SNPs) from the NPPA/NPPB locus. Haplotype population frequencies were estimated and adjusted haplotype trait associations for brain natriuretic peptide (BNP) and amino-terminal pro natriuretic peptide (NT-proBNP) were calculated. Five SNPs were included in the analysis. Compared to the reference haplotype TATAT (rs198358, rs5068, rs632793, rs198389, rs6676300), haplotype CACGC, with an estimated frequency of 4%, showed elevated BNP and NT-proBNP plasma concentrations by 44% and 94%, respectively. Haplotype CGCGC, with an estimated frequency of 9%, lowered NT-proBNP concentrations by 28%. ASA classification status III and IV, as well as coronary artery disease, were the strongest predictors of increased NP plasma levels. Inclusion of genetic information might improve perioperative risk stratification of patients based on adjusted thresholds of NP plasma levels.

Arrhythmogenic right ventricular cardiomyopathy patients with a markedly enlarged RV compressing LV to left side have an atypical distribution of epsilon waves and elevated plasma BNP

Abstract Funding Acknowledgements Type of funding sources: None. Background Epsilon waves on V1-3 leads are specific ECG findings in patients with arrhythmogenic right ventricular (RV) cardiomyopathy (ARVC) suggesting RV conduction delay. Four dimensional (4D) cardiac CT visualizes ARVC characteristics, such as fibro-fatty invasion into RV and left ventricular (LV) myocardium (RVM, LVM), an enlarged RV, reduced RV motion, and bulging. Purpose We hypothesize that Epsilon waves in V4-6 leads suggest LV invasion in ARVC. Alternatively, extreme RV enlargement may compress the LV and cause clockwise rotation; an enlarged RV may itself cause epsilon waves in V4-6 leads. Methods Retrospective analysis of 17 patients (11 males, 57 ± 17 yrs) with suspected ARVC undergoing cardiac CT and ECG, 9 of whom met 2010 ARVC task force criteria. Results All 9 patients had epsilon waves on ECG; 5 had fibro-fatty invasion into the LVM. We divided the 9 into 5 groups by CT: 1) markedly enlarged RV compressing the LV to the left side with fibro-fatty changes exclusively in RVM (N = 1); 2) similar findings in both RVM and LVM (N = 2); 3) moderately enlarged RV without compression of the LV to the left side and fibro-fatty changes exclusively in RVM (N = 3); 4) the same in both RVM and LVM (N = 2); 5) severe mitral valve regurgitation, a markedly enlarged LV, and a fibro-fatty change in both RVM and LVM (N = 1). The patient in group (gp) 1 showed epsilon waves in V1-6 leads, patients in gp 2 had epsilon waves in V1-6 (N = 1), and V3-5 (N = 1) leads; patients in gp 3 had epsilon waves in V1-4 (N = 2), and V1-3 (N = 1) leads, patients in gp 4 had epsilon waves in V1-3 (N = 1), and V1, 2 (N = 1) leads; finally, the patient in gp 5 had epsilon waves in V4-6 leads. Plasma brain natriuretic peptide (BNP) levels were significantly greater in patients in gp 1 & 2 than gp 3 & 4 (1255 ± 838 vs 80 ± 52 pg/ml, P = 0.016). Conclusions ARVC patients with a markedly enlarged RV compressing the LV to the left side (gp 1,2) had a broad (V1-6) or different range (V3-5) distribution of epsilon waves and significantly elevated plasma BNP independent of fibro-fatty invasion of the LV, different from typical ARVC (gp 3,4). Additionally, structural change due to complicated heart disease, such as valvular disease (gp5), may also influence the distribution of epsilon waves in ARVC. Abstract Figure. CT and ECG in ARVC group 1

Two-dimensional echocardiographic scoring system of the left ventricular filling pressure and clinical outcomes in heart failure with preserved ejection fraction

Abstract Funding Acknowledgements Type of funding sources: Public Institution(s). Main funding source(s): Japan Society for the Promotion of Science (JSPS) Introduction Elevated left ventricular (LV) filling pressure in non-decompensated state is a powerful indicator of worse clinical outcomes in heart failure regardless of LV ejection fraction. However, its detection is often challenging in heart failure with preserved ejection fraction (HFpEF). Purpose This study aimed to elucidate the predictive value of recently proposed echocardiographic parameter of LV filling pressure, Visually assessed time difference between the Mitral valve and Tricuspid valve opening (VMT) score in HFpEF. Methods We retrospectively analyzed 310 well-differentiated HFpEF patients in stable conditions. Using two-dimensional echocardiographic images, time sequence of opening of mitral valve and tricuspid valve was visually assessed in the apical four-chamber view and scored to 0 to 2 (0: tricuspid valve first, 1: simultaneous, 2: mitral valve first). When the inferior vena cava diameter was dilated, 1 point was added and VMT score was calculated as four grades from 0 to 3. Based on the previous study, VMT≥2 was regarded as a sign of elevated LV filling pressure (Figure 1). LV diastolic function was graded according to the guidelines. The primary endpoint was defined as a composite of cardiac death and heart failure hospitalisation during the two years after echocardiographic examination. Results During the follow-up period, 55 events (18%) occurred, including four cardiac deaths and 51 heart failure hospitalisations. Kaplan-Meier curves demonstrated that VMT≥2 (n = 54) was associated with worse outcomes compared to patients showing VMT ≤ 1 (n = 256) (log-rank test P <0.001). Furthermore, VMT≥2 was associated with worse outcomes when tested in 100 HFpEF patients with atrial fibrillation (log-rank test P = 0.026) (Figure 2). In the adjusted model including age, systolic blood pressure, serum albumin level, and the LV diastolic function grading, VMT≥2 was independently associated with the primary outcome (hazard ratio: 2.23; 95% confidence interval: 1.17 to 4.24, P = 0.014). Additionally, the nested regression model showed that VMT scoring provided an incremental prognostic value over clinically relevant variables (age, sex, the plasma brain natriuretic peptide level, atrial fibrillation) and LV diastolic function grading (chi-square 10.8 vs 16.3, P = 0.035). Conclusions In patients with HFpEF, the VMT score was independently and incrementally associated with adverse clinical outcomes. Moreover, it discriminated worse clinical outcome even in HFpEF patients with atrial fibrillation. Abstract Figure. VMT scoring Abstract Figure. Kaplan-Meier analysis

Elevated standardised uptake value of the free wall of the right ventricular myocardium is correlated with enlarged left ventricular end-diastolic volume among patients with heart failure with reduced ejection fraction: A retrospective study.

This study aimed to investigate the relationship between the standardised uptake value of the free wall of the right ventricular myocardium (SUVrv) and left ventricular end-diastolic volume (LVEDV) among patients with heart failure with reduced ejection fraction (HFrEF) with coronary artery disease (CAD). This retrospective study included 50 patients with CAD and HFrEF scheduled for cardiac viability imaging with electrocardiography-gated fluorine-18-fluorodeoxyglucose (18F-FDG) positron emission tomography/computed tomography (PET/CT). The maximal SUVrv was measured. The LVEDV and left ventricular ejection fraction (LVEF) were automatically measured using quantitative gated single-photon emission computed tomography. Plasma brain natriuretic peptide (BNP) levels were obtained from medical records.The LVEF (0.24±0.06) was markedly reduced while the LVEDV (201.5±59.9mL) and BNP level (1348.1±1382.9pg/mL) were remarkably elevated. The SUVrv was 3.7±1.7 and was similar between patients with and without diabetes. The SUVrv was significantly positively correlated with the LVEDV and BNP level (r=0.35, 0.45; P=0.01, ≤0.01, respectively) but was unrelated to the LVEF (r=0.11, P=0.44). Herein, SUVrv was elevated and significantly positively correlated with LVEDV and BNP levels among patients with CAD and HFrEF but was unrelated to LVEF and diabetic status.

Left Atrial Appendage Confusion: A Mobile Echodensity in a Patient With Endocarditis

A 50-YEAR-OLD, 70- kg, 172- cm man with known bicuspid aortic valve disease and severe aortic insufficiency presented to the authors’ institution with a 3-day history of “pulsating” chest pain, dyspnea with exertion, and bilateral lower extremity swelling. The patient previously was hospitalized on several occasions for the treatment of recurrent Streptococcus cristatus bacteremia originating from poor dentition. He also was receiving apixaban for the treatment of a cephalic vein thrombosis. The physical examination was notable for sinus tachycardia (122 beats/min), grade III/VI systolic and diastolic murmurs heard best at the left sternal border, bilateral lower extremity pitting edema, and red petechiae on both hands and feet. The patient was anemic (hemoglobin of 8.0 g/dL) and had renal insufficiency (serum creatinine concentration of 1.66 mg/dL). Leukocytosis was present (11.8 103/µL). The plasma brain natriuretic peptide level was markedly elevated (20,063 pg/mL). An increase in high-sensitivity troponin concentration also was observed. An electrocardiogram revealed sinus tachycardia and low-voltage QRS complexes, but acute ST-segment changes were absent. Transthoracic echocardiogram revealed vegetations on both the aortic and mitral valves, resulting in severe regurgitation. Transesophageal echocardiography (TEE) also was performed as part of the diagnostic evaluation, and the following images were obtained (Fig. 1-3; Videos 1-3). What is the diagnosis?

Utility of perinatal natriuretic peptide for predicting neonatal heart failure.

We evaluated the significance of perinatal plasma natriuretic peptide (NP) levels in neonates with congenital heart defects (CHDs) or arrhythmias and determined whether measurement of perinatal plasma NP levels and echocardiographic assessment in utero could predict heart failure after birth. The study was conducted between 2012 and 2016 to evaluate the correlation of perinatal atrial NP (ANP) and brain NP (BNP) levels at birth with the modified Ross score after birth and the cardiovascular profile (CVP) score before birth. A total of 122 singletons with CHDs or arrhythmias and 27 controls were analyzed. Neonatal blood sampling was performed at a median of 0.7 h (range, 0.1-1.5) after birth. The neonatal plasma ANP and BNP levels shortly after birth were significantly higher than those in the umbilical artery (UA) plasma. The ANP and BNP levels in UA and neonatal blood were correlated with the modified Ross score. The neonatal plasma ANP and BNP levels and the modified Ross scores were inversely correlated with the CVP score in neonates with CHDs or arrhythmias. The area under the receiver operating characteristic curve of UA ANP levels for predicting neonatal heart failure was highest among those for the CVP score, perinatal plasma ANP and BNP levels, and their combinations. The plasma ANP and BNP levels increased markedly shortly after birth. Assessment of the UA plasma ANP level at birth and the CVP score in utero may be utilized to predict neonatal heart failure.

The regulation of BNP transcription and DNA methylation modification in anticancer drug-induced cardiomyocyte toxicity.

Background) Genomic DNA, which contains all of the genetic information, is damaged by a variety of endogenous and environmental factors such as genotoxic chemicals, ionizing radiation and UV light. Consequently, the DNA repair process is constantly active as it responds to damage in the DNA structure. Not only cardiotoxicity of anticancer drug treatment but also ischemic heart disease and heart failure associated with overloaded pressure interfere with DNA damage response and DNA repair regulation in cardiomyocytes. We have reported that anticancer drug treatment causes a transient decrease in plasma brain natriuretic peptide (BNP) levels, but the mechanism of this decrease is unknown. In the present study, to clarify this molecular mechanism, we analyzed mouse hearts treated with anticancer drugs. Methods) C57BL/6 mice were treated with cisplatin (16 mg/kg, ip), and then BNP gene expression and DNA methylation in the heart were examined. Results) In cisplatin-treated mice, there was a transient decrease in BNP gene expression and an increase in DNA methylation of the BNP promoter region. Furthermore, DNA methyltransferase type 1 (DNMT1) was found to affect this DNA methylation. Conclusions) In cisplatin-treated mice, cardiac BNP transcription was repressed by DNA methylation. DNMT1 was suggested to be involved in this DNA methylation modification.

Analysis of correlation between heart failure in the early stage of acute myocardial infarction and serum pregnancy associated plasma protein-A, prealbumin, C-reactive protein, and brain natriuretic peptide levels.

The study sought to analyze the predictive value of the early measurement of pregnancy associated plasma protein-A (PAPP-A), prealbumin (PAB), C-reactive protein (CRP), brain natriuretic peptide (BNP), and other indicators of heart failure (HF) after acute myocardial infarction (AMI). A total of 200 AMI patients admitted to Wuyi People's Hospital from November 1, 2019 to October 31, 2020 were continuously enrolled as the research objects and divided into a HF group (Killip class II or above, n=94) and HF-free group (Killip class I or below, n=106) according to the Killip Classification for Heart Function. The age, creatine kinase-myocardial band (CK-MB), PAPP-A, CRP, suppression of tumorigenicity 2 (ST2), BNP, aldosterone (ALD), and left ventricular end-diastolic diameter (LVEDD) of the HF group were all significantly higher than those of the HF-free group, while the PAB and left ventricular ejection fraction (LVEF) were significantly lower (P<0.05). The PAPP-A, CRP, and BNP of HF patients increased as the Killip class increased, while the PAB decreased progressively (P<0.05). After including the statistically significant single factors in a multivariate logistic regression analysis, it was found that PAPP-A, PAB, CRP, and BNP were the independent influencing factors causing HF in the early stage of AMI; and the diagnostic efficacy of HF in the early stage of AMI (from high to low) was combined test, PAPP-A, PAB, BNP and CRP. Serum PAPP-A, PAB, CRP and BNP levels are the independent influencing factors of HF after AMI, but comprehensive tests of clinical indicators, including PAPP-A, PAB, CRP, and BNP, are more accurate at predicting and evaluating HF and can be used to guide clinical decisions.

Brain Natriuretic Peptide Levels in Hypertensive Heart Failure Patients with and without Diabetes Mellitus: A Cross-sectional Study

Introduction: Heart Failure (HF) is a major disorder causing mortality and morbidity in the elderly population. Brain Natriuretic Peptide (BNP) is considered as the gold standard biomarker for diagnosis of HF. Aim: To find the association of plasma BNP levels with heart failure in hypertensive patients with and without diabetes mellitus. Materials and Methods: This cross-sectional study consisted of 35 hypertensive heart failure patients who attended the Outpatient General Medicine Department at Sri Ramachandra Medical College and Research Institute, Chennai, Tamil Nadu, India, between March 2020 to December 2020. The patients who belonged to class IV heart failure of the New York heart association were included. Total 35 HF patients were divided into two groups. Group 1 included 10 patients with hypertensive heart failure without diabetes mellitus. Group 2 included 25 patients with hypertensive heart failure with diabetes mellitus. Parameters such as Systolic Blood Pressure (SBP), Diastolic Blood Pressure (DBP), waist to hip ratio, Body Mass Index (BMI), Ejection Fraction (EF), transmitral filling velocities (E/A ratio), Left Ventricular Posterior Wall Thickness (LVPW), Left Ventricular Internal Dimension in diastole (LVIDd) and BNP level, random plasma glucose and HbA1c % were assessed in all the patients. Student’s t-test and Mann-Whitney U test were used to statistically analyze the data and p-value ≤ 0.05 was considered statistically significant. Results: Mean age of patients were 65.80±12.72 years in group 1 and 66.56±11.72 years in group 2. All patients in group 1 and most of the patients in group 2 (15,42%) were males. All the patients were in the obese category (BMI&gt;27 kg/m2 ). Serum BNP level was 1365 (243-3680) ng/L in group 1 and 691 (44.7-4261) ng/L in group 2, but this difference was not statistically significant (p-value=0.23). Echocardiography showed significant differences in left ventricular internal dimension in diastole, left ventricular posterior wall thickness and E/A ratio-integrated between hypertensives and hypertensives with diabetes mellitus. Serum BNP had a significant positive correlation with systolic blood pressure (r=0.33, p-value=0.05). There were highly significant differences in random plasma glucose and glycated haemoglobin between the groups. Conclusion: Plasma BNP levels were associated with systolic blood pressure in heart failure patients with hypertension. The significance of association is the same in hypertensives with diabetes mellitus. Thus, BNP as a biomarker plays a major role in the prediction of heart failure. But BNP could not differentiate whether the heart failure was due to hypertension alone or due to associated metabolic conditions.

Plasma brain natriuretic peptide, platelet parameters, and cardiopulmonary function in chronic obstructive pulmonary disease.

BACKGROUNDChronic obstructive pulmonary disease (COPD) is a chronic respiratory disease with worldwide occurrence and high disability and mortality rate. It occurs mostly in the elderly population with pulmonary heart disease, type II respiratory failure, and other serious complications.AIMTo investigate the correlation of plasma brain natriuretic peptide (BNP) and platelet parameters with cardiac function and pulmonary hypertension in patients with COPD and pulmonary heart disease. METHODSFrom June 2016 to June 2019, 52 patients with COPD-pulmonary heart disease (pulmonary heart disease group), 30 patients with COPD (COPD group), and 30 healthy individuals (control group) in our hospital were enrolled in the study. The pulmonary heart disease group was further divided into subgroups according to cardiac function classification and pulmonary artery pressure. Plasma BNP and platelet parameters were estimated and compared among each group and subgroup. The correlation of plasma BNP and platelet parameters with cardiac function classification and pulmonary artery pressure was then analyzed.RESULTSIn the pulmonary heart disease group, the COPD group, and the control group, the levels of plasma BNP, platelet distribution width (PDW), and mean platelet volume (MPV) showed a decreasing trend (P < 0.05), while an increasing trend was found in platelet count (PLT) and plateletcrit (PCT) levels among the three groups (P < 0.05). In the pulmonary hypertension mild, moderate, and severe subgroups, the levels of plasma BNP, PDW, and MPV showed an increasing trend (P < 0.05), while a decreasing trend was observed in PLT levels (P < 0.05); however, PCT levels showed no significant difference among the three subgroups (P > 0.05). In the cardiac function grade I, II, III, and IV subgroups, the levels of plasma BNP, PDW, and MPV showed an increasing trend (P < 0.05), while a decreasing trend was noted in PLT and PCT levels among the four subgroups (P < 0.05). Correlation analysis showed that the levels of plasma BNP, PDW, and MPV in patients with pulmonary heart disease were positively correlated with their pulmonary artery pressure (P < 0.05), while PLT was negatively correlated with their pulmonary artery pressure (P < 0.05). Moreover, plasma BNP, PDW, and MPV levels were positively correlated with cardiac function grade (P < 0.05) of these patients, while PLT and PCT levels were negatively correlated with their cardiac function grade (P < 0.05).CONCLUSIONPlasma BNP and PLT parameters are significantly correlated with the cardiac function and pulmonary hypertension in patients with COPD and pulmonary heart disease, indicating that these parameters have high clinical relevance in reflecting the health condition of these patients and for guiding their treatment.

Thyroid Storm Patients With Elevated Brain Natriuretic Peptide Levels and Associated Left Ventricular Dilatation May Require Percutaneous Mechanical Support.

OBJECTIVES:To determine the characteristics of thyroid storm patients with acute decompensated heart failure who should be candidates for temporary percutaneous mechanical circulatory support in addition to beta-blocker treatment to prevent cardiogenic shock.DESIGN:A single-center, retrospective review of treatment details and data collected from electronic medical records.SETTING:Thyrotoxicosis complicated with acute decompensated heart failure.PATIENTS:Eight consecutive patients who were admitted to our hospital for acute decompensated heart failure with thyroid storm between December 2011 and August 2020 were retrospectively reviewed. Of the eight patients, four were treated with percutaneous mechanical circulatory support.INTERVENTIONS:None.MEASUREMENTS AND MAIN RESULTS:Compared with thyroid storm patients who did not require percutaneous mechanical circulatory support, those who did had a significantly higher initial plasma brain natriuretic peptide level (1,231 [911–3,387] vs 447 pg/mL [243–653 pg/mL], respectively; p = 0.015), as well as a significantly larger left ventricular end-diastolic diameter (56 [54–63] vs 48 mm [38–48 mm], respectively; p = 0.029) and end-systolic diameter (50 [49–58] vs 28 mm [28–30 mm], respectively; p = 0.029) on echocardiogram. In terms of thyroid storm severity, the Burch-Wartofsky score was higher in patients with percutaneous mechanical circulatory support than in those without, although the difference was not significant. All patients survived this index admission.CONCLUSIONS:In thyroid storm patients, the presence of a high brain natriuretic peptide level, “left ventricular dilatation,” or both may necessitate hemodynamic assessment to determine the indication of percutaneous mechanical circulatory support before beta-blocker administration.

Dementia associated with chronic kidney disease is accompanied by increase in plasma amyloid beta and cardiovascular dysfunction.

In end-stage chronic kidney disease (CKD) the prevalence of cognitive impairment (CI) has been estimated at 30-60%. Cardiovascular diseases (CVD) including increased central arterial stiffness (CAS) accompany CKD development. CAS drives pulse pressure (PP) and pulsatile component index (PCI) increases and cerebral microvascular damage resulting in a reduction of blood supply to the brain hereby contributing to CI. Elevated PP and PCI are associated with higher mortality in CVD and CKD independently of BP. The aim of the study was to determine whether CKD potentiates CI development due to CAS and the resultant increase in the PCI, a major contributor to brain and renal microvasculature damage. Measurements of systolic and diastolic blood pressure (SBP, DBP), echocardiography (ECHO), plasma amyloid beta-40 (Aβ-40), BUN, creatinine, aspartate aminotransferase (AST), brain natriuretic peptide (BNP), and mini-mental status examination (MMSE) were performed in 25 patients with stage IV CKD and in 22 age- and sex-matched healthy controls (Table 1). PCI was calculated as a function of SBP and DBP. The data were analyzed by unpaired two-tailed t-test, Pearson correlation with P values adjusted for false discovery rate, and are presented as mean±SEM. CKD patients had higher SBP, PP, PCI, LV systolic and diastolic volume, lower LV ejection fraction, higher plasma BNP and AST (CVD markers), plasma Aβ-40 (Alzheimer's disease marker), BUN and creatinine (CKD markers) and lower score in MMSE vs. healthy control (Table 1). Cognitive test results positively correlated with LV stroke volume, negatively correlated with PCI, a measurement of pulsatility of BP, and negatively correlated with plasma ASP, a marker of CVD (Table 2). SBP and DBP did not correlate with cognitive parameters. Further investigation of the possible metabolic role of Aβ-40 in the development of CI in CKD patients, and whether plasma AST can be a marker of CI in CKD, will be assessed in the future studies. Higher PP, PCI and lower score in MMSE in CKD patients supports our hypothesis that cardiovascular remodeling in CKD is a key component of CI progression. Supported by the NIH Grant 1R15HL150721 (K.S.), and in part by NIH/NIA Intramural Research Program.

Aetiological classification and prognosis in patients with heart failure with preserved ejection fraction.

AimsHeart failure with preserved ejection fraction (HFpEF) is a heterogeneous syndrome with various causes that may influence prognosis.Methods and resultsWe extracted the electronic medical records for 2180 consecutive patients hospitalized between 2016 and 2019 for decompensated heart failure. Using a text mining algorithm looking for a left ventricular ejection fraction ≥50% and plasma brain natriuretic peptide level >100 pg/mL, we identified 928 HFpEF patients. We screened for a prevailing cause of HFpEF according to European guidelines and found that 418 (45.0%) patients had secondary HFpEF due to either myocardial (n = 125, 13.5%) or loading condition abnormalities (n = 293, 31.5%), while the remaining 510 (55.0%) patients had idiopathic HFpEF. We assessed the association between the causes of HFpEF and survival collected up to 31 December 2020 using Cox proportional hazards analysis. Even though patients with idiopathic HFpEF were older, frequently female, and had frequent co‐morbidities and a higher crude mortality rate compared with secondary HFpEF patients, their prognosis was similar after adjustment for age and sex. Unsupervised clustering analysis revealed three main phenogroups with different distribution of idiopathic vs. secondary HFpEF. The phenogroup with the highest proportion of idiopathic HFpEF (69%) had (i) an excess rate of non‐cardiac co‐morbidities including chronic obstructive pulmonary disease (31%) or obesity (41%) and (ii) a better prognosis compared with the two other phenogroups enriched with secondary HFpEF.ConclusionsAetiological classification provides clinical and prognostic information and may be useful to better decipher the clinical heterogeneity of HFpEF.

Abstract 9185: Diagnostic Utility of R-R Interval Variations Under Deep Breathing Load in Patients With Cardiac Amyloidosis

Introduction: Autonomic disorder is one of important characteristics of cardiac amyloidosis. However, the prevalence of autonomic disorder in wild-type transthyretin amyloidosis (ATTR wt ) remains to be elucidated. Analysis of coefficient of variation of R-R interval (CVR-R) is a non-invasive method to measure the autonomic nervous system. In normal subjects, CVR-R values are higher during deep breathing load than those at rest. Diminished response of CVR-R to deep breathing reflects the parasympathetic nervous system disorder. We aimed to assess autonomic disorder of ATTRwt and investigate the utility of CVR-R for the detection of ATTRwt from other cardiac disease. Methods: Fifty patients with chronic heart failure (HF) patients aged &gt;70 were investigated. The etiology of HF was as follows: ATTR wt , n=10; previous myocardial infarction (MI), n=20; and left ventricular hypertrophy (LVH) due to other disease (e.g. aortic stenosis); n=20. Serum cardiac troponin I and plasma brain natriuretic peptide (BNP) were measured in all patients. Cardiac function was evaluated by echocardiography. We measured CVR-R at rest (CVR-R rest ), CVR-R with deep breaths (CVR-R beath ) and their change rate (CVR-R diff rate ). Relative change formula is CVR-R diff rate = (CVR-R beath - CVR-R rest )/ CVR-R rest . Results: There was no difference in age among the three groups. Plasma BNP levels, troponin I levels and left ventricular mass index were significantly higher in ATTR wt group. There was no difference in CVR-R rest levels among the three groups. CVR-R diff rate levels in ATTR wt group were significantly lower (ATTR wt : -8.77 [-43.8-10.9]; LVH: 67.4 [38.7-89.4]; MI: 83.7 [60.4-142.9], respectively). In the ROC analysis to identify ATTR wt in HF, the best cutoff value for CVR-R diff rate was 1.197 (AUC: 0.848). Conclusions: Autonomic nervous disorder is frequently observed in the patients with ATTR wt . Measurement of CVR-R is convenient support tool for detection of ATTRwt.

Breath acetone concentration: too heterogeneous to constitute a diagnosis or prognosis biomarker in heart failure? A systematic review and meta-analysis

Introduction. Exhaled breath acetone (ExA) has been investigated as a biomarker for heart failure (HF). Yet, barriers to its use in the clinical field have not been identified. The aim of this systematic review and meta-analysis was to assess the ExA heterogeneity and factors of variability in healthy controls (HC), to identify its relations with HF diagnosis and prognostic factors and to assess its diagnosis and prognosis accuracy in HF patients. Methods. A systematic search was conducted in PUBMED and Web of Science database. All studies with HC and HF patients with a measured ExA were included and studies providing ExA’s diagnosis and prognosis accuracy were identified. Results. Out of 971 identified studies, 18 studies involving 833 HC and 1009 HF patients were included in the meta-analysis. In HC, ExA showed an important heterogeneity (I 2 = 99%). Variability factors were fasting state, sampling type and analytical method. The mean ExA was 1.89 times higher in HF patients vs. HC (782 [531–1032] vs. 413 [347–478] ppbv; p < 0.001). One study showed excellent diagnosis accuracy, and one showed a good prognosis value. ExA correlated with New York Heart Association (NYHA) dyspnea (p < 0.001) and plasma brain natriuretic peptide (p < 0.001). Studies showed a poor definition and reporting of included subjects. Discussion. Despite the between-study heterogeneity in HC, the evidence of an excellent diagnosis and prognosis value of ExA in HF from single studies can be extended to clinical populations worldwide. Factors of variability (ExA procedure and breath sampling) could further improve the diagnosis and prognosis values of this biomarker in HF patients.

Abstract 11925: Comparison of Right Ventricular Outflow Tract-Dominant Hypertrophic Type With Diffuse Type Using Cardiac CT for J Waves and Clinical Parameters in Pulmonary Hypertensive Patients

Introduction: J waves are specific in patients with hypothermia, idiopathic ventricular fibrillation, or brain damage. Patients with pulmonary hypertension (PH) may show right ventricular (RV) hypertrophy and fibrosis, leading to abnormal ECG findings. On cardiac CT of PH, two RV hypertrophic (RVH) types are seen, namely RV outflow tract dominant and RV diffuse. Hypothesis: We hypothesize that these two morphological RVH types might have different effects on ECG findings including J waves, and clinical severity in PH patients. Method: We retrospectively analyzed 43 PH patients (33 females, 55±15 yrs, 31 chronic thromboembolic PH, 7 idiopathic pulmonary arterial (PA) hypertension). Cases were divided into 3 groups: RV outflow tract dominant RVH (gp 1) (N=6), RVH diffuse (gp 2) (N=26), and no RVH (gp 3) (N=11). Results: In gp 1, one (17%) had J waves in II, III, and aVF leads with a maximum RV wall thickness on end-diastole 7.5mm. In gp 2, three (12%) had J waves in II, III, and aVF leads with maximum RV wall thickness on end-diastole 6.7, 6.1, and 5.6mm, respectively. In gp 3, none (0%) had J waves. In gp 1, all six (100%) had a negative T wave in V1-3 leads or beyond and in gp 2, 24 (92%) had a negative T wave in V1-3 leads or beyond (P=0.483). There were significant positive correlations between maximum RV wall thickness in end-diastole and plasma brain natriuretic peptide (BNP) in gp 1 (R=0.44) but no correlations in gp 2. There were significant positive correlations between maximum RV wall thickness in end-diastole and estimated PA systolic pressure (PASP) on TTE in gp 1 (R=0.38) but no correlations in gp 2. Conclusions: In 32 PH participants with an organized RV myocardial change, such as RV outflow tract dominant and diffuse type RVH, 17% and 12% had J waves in II, III, and aVF leads and most of them had a negative T wave in V1-3 leads or beyond. Only RV outflow tract dominant RVH showed significant positive correlations between maximum RV wall thickness in end-diastole, plasma BNP and estimated PASP.

Abstract 10993: Prognostic Value of Low T 3 Syndrome in Patients with Acute Decompensated Heart Failure in Osaka Prefectural Acute Heart Failure Registry (OPAR)

Backgrounds: It is widely recognized that thyroid dysfunction is a potential cause of heart failure (HF). In HF, one of the alterations of thyroid functions is referred to as low T 3 syndrome marked by a reduction in serum free triiodothyronine (T 3 ) with normal levels of thyroid-stimulating hormone (TSH). However, there is little information available about the association between low T 3 syndrome and future cardiac events in patients with acute decompensated heart failure (ADHF), relating to left ventricular ejection fraction (LVEF). Methods and Results: We studied 565 patients admitted for ADHF with survival discharge in our prospective cohort study. Laboratory data including free T 3 , thyroxine and TSH were obtained at discharge. Among the patients with euthyroid (0.35 μU/mL &lt;TSH &lt;4.94 μU/mL, n=438), there was 62 patients who were diagnoses as low T 3 syndrome (free T 3 ≦1.68 pg/mL). The primary end point of this study was all-cause death (ACD). During a mean follow up period of 2.9±1.4 years, 121 patients died. Study subjects were stratified into two LVEF subgroup as follows; 239 patients had LVEF&lt;50% (HFrEF), and 199 patients had LVEF≧50% (HFpEF). While 68 HFrEF parients died, 53 HFpEF patients died. Kaplan-Meier curve analysis revealed that patients with the low free T 3 group had the greater risk of ACD than those with the normal free T 3 group in both LVEF subgroup (log-rank p=0.0233 in HFrEF and p=0.0265 in HFpEF). Multivariate Cox analysis showed that free T 3 was significantly associated with ACD after multivariable adjustment for major confounders, such as age, sex, systolic blood pressure and plasma brain natriuretic peptide level in both LVEF subgroup (p=0.0039 in HFrEF, p=0.0487 in HFpEF). Conclusion: Low T 3 syndrome was significantly associated with poor outcome in ADHF patients with both HFrEF and HFpEF.

Abstract 10027: Pulsatile Load, Rather Than Cardiac Power Output, for the Right Ventricle Determines the Prognosis in Heart Failure Patients

Background: Although cardiac power output (CPO), a parameter of cardiac performance, for the left ventricle (LV) is reported to be a powerful prognostic indicator in heart failure (HF), significance of the right ventricular (RV) CPO in HF has not been elucidated. On the other hand, RV pulsatile load stands for one of the prognostic markers in HF. We thus investigated the relationship of the RV CPO and pulsatile load to the outcome in HF. Methods: Right heart catheterization and echocardiography were performed in 231 HF patients (62±16 years, LV ejection fraction 42±18%). Invasive and noninvasive CPOs were calculated from mean systemic or pulmonary arterial pressures and cardiac output for the LV and RV. LV CPO was then corrected by LV mass (LV CPO/M). Pulmonary artery compliance (PAC) and the ratio of acceleration time to ejection time (AcT/ET) of the RV outflow velocity were used as parameters of RV pulsatile load. Cardiac death, HF hospitalization, ventricular arrhythmia and LVAD implantation after the examination were recorded. Results: Noninvasive CPOs were moderately correlated with invasive ones (LV: R=0.73, RV: R=0.58, P &lt;0.001 for both). During a median follow-up period of 441 days, cardiac events occurred in 57 patients. Using the cut-off of median values, lower LV CPO/M was associated with higher event rates, however, RV CPO did not discriminate the risk of future cardiac events. In contrast, higher RV pulsatile load was associated with higher event rates regardless of the level of LV CPO/M ( Figure ). In multivariable Cox proportional hazard analyses, echocardiographic LV CPO/M and AcT/ET both determined cardiac events independently of age, NYHA classification, LV ejection fraction and plasma brain natriuretic peptide levels. Conclusion: Pulsatile load, rather than CPO, for the RV was associated with cardiac events in HF. Furthermore, combination of echocardiographic LV CPO/M and AcT/ET could become a novel noninvasive prognostic indicator in HF patients.

Abstract 10769: Osteoprotegerin and Incident Heart Failure: The Atherosclerosis Risk in Communities Study

Background: Osteoprotegerin (OPG), a protein involved in bone metabolism, is associated with cardiac fibrosis and remodeling in animal models. Circulating OPG levels correlate with left ventricular mass index and plasma brain natriuretic peptide levels in humans, but the association with incident heart failure (HF) is not known. Methods: Among 10,261 participants in the community-based Atherosclerosis Risk in Communities (ARIC) Study free of prevalent HF at study Visit 3, we investigated the association of plasma OPG levels at Visit 3 with incident HF hospitalization post-Visit 3 using multivariable Cox proportional hazard models. OPG was measured using a high-throughput DNA aptamer-based proteomic platform (Somalogic, Boulder, CO), and relative fluorescence unit values were log2 transformed. All models adjusted for age, sex, race, study field center, body mass index, hypertension, diabetes, estimated glomerular filtration rate, smoking status, prevalent coronary artery disease, and atrial fibrillation. Results: Mean age was 60±6 years, 54% were women, and 20% of participants were Black. Higher OPG levels were associated with older age, female gender, Black race, and higher prevalence of hypertension, diabetes, and smoking (all p &lt;0.001). Over a median of 15.0 years follow-up (interquartile range: 13-15), there were 1301 incident HF hospitalizations. In multivariable models, higher serum OPG levels were associated with greater risk of incident HF (hazard ratio per 1 SD increase: 1.20 [95% confidence interval, 1.13-1.27]; Figure). This association persisted after further adjustment for NT-proBNP (HR 1.19 [95% CI 1.12-1.26], p&lt;.001). Conclusion: In this large community-based cohort, higher plasma OPG levels were significantly associated with incident HF hospitalization, independent of traditional cardiovascular risk factors and NT-proBNP. Further studies are warranted to clarify whether OPG could be a new therapeutic target for HF prevention.

Association macrophage subpopulation with cardiac biomarkers in patients with acute decompensated ischemic heart failure with reduced ejection fraction

Abstract Objective To determine the association macrophage subpopulation with cardiac biomarkers (interleukin (IL)-1β, IL-6, IL-10, highly sensitive C-reactive protein (hsCRP), tumor necrosis factor alpha (TNF-α), troponin I, interferon gamma (IFN-γ), plasma brain natriuretic peptide (BNP), and N-terminal fragment of precursor protein brain-type natriuretic peptide (NT-proBNP), soluble interleukin 1 receptor-like 1 (ST2)) in patients with acute decompensated ischemic heart failure with reduced ejection fraction. Methods This open-label, nonrandomized, single-center, prospective trial was registered at clinicaltrials.gov (#NCT02649517) and included 25 patients (84% men, LVEF of 29.17±9.4%) with ADHF. Inclusion criteria were ADHF, not earlier than 6 months after optimal surgery (PCI or/and CABG) and optimal drug treatment for ADHF according to ESC guidelines. Invasive coronary angiography was performed in all patients to exclude the progression of coronary atherosclerosis. All patients underwent endomyocardial biopsy (EMB) with immunohistochemically analysis for diagnostic myocarditis. Macrophage infiltration in the heart was assessed by double immunofluorescence. CD68 was a marker for the cells of the macrophage lineage, CD80 was considered as M1-like macrophage and CD163, CD206, stabilin-1 were as M2-like macrophage biomarkers. Each area was evaluated in 5 random fields. On admission serum levels of IL-1β, IL-6, IL-10, hsCRP, TNF-α, troponin I, IFN-γ, ST2, BNP, and NT-proBNP were measured using enzyme-linked immunosorbent assay (ELISA). The double immunofluorescence has not been performed in 4 patients. Results An association was found between CD68+/CD80+ macrophages and level of TNF-α (r=0.512, p=0.042) in all patient. After EMB, all patients were divided into 2 groups. Group 1 comprised 16 patients (64%) with myocarditis; group 2 comprised 9 patients (36%) without myocarditis. In group 1 the association was found between CD68+/CD80+ macrophages and the level of troponin I (r=0.874, p=0.05). Besides, the association was revealed CD68-/CD206+ macrophages with the level of hsCRP (r= - 0.755, p=0.03), and CD163-/CD206+ macrophages with the level of IL-6 (r=0.843, p=0,009) in group 1. CD68-/stabilin-1 macrophages were in direct correlation with level of NT-proBNP (r=0.790, p=0.02) and in inverse correlation with level of troponin I (r= - 0.711, p=0.05) in group 1. In group 2 the association was found between CD68-/CD206+ macrophages and the level of ST2 (r=0.0.537, p=0.037). Conclusion Our data suggest that many associations identified between M1-like macrophages (CD 68+/CD 80+), M2-like macrophages (CD68-/CD206+, CD163-/CD206+) and markers of inflammation (hsCRP, IL-6) and myocardial damage (NT-proBNP, troponin I) in patients with myocarditis. Whereas in patients without myocarditis, only the association of M2-like macrophages (CD68-/CD206+) with the ST2 level was revealed, probably due to the continuing unfavorable remodeling of the heart. Funding Acknowledgement Type of funding sources: None.