Plasma Brain Natriuretic Peptide Levels Research Articles

Kord Kanı ve Yenidoğan Plazma Beyin Natriüretik Peptid Düzeyleri ile Doğum Şekli Arasındaki İlişki

Fetal-to-neonatal adaptation involves many complex mechanisms. Cardiovascular biomarkers may help to understand fetal and maternal physiology in pregnancy and during the perinatal transition period. In this present study, our aim was to assess the association between delivery type and brain natriuretic peptide (BNP) levels in healthy full-term neonates. Forty-eight neonates born by vaginal delivery (n=25) and cesarean section (n=23) were included in the study. Plasma BNP levels were measured at cord blood samples. In addition antropometric measurements and physical examination were evaluated at first day of life. BNP levels measure and clinical evaluation were repeated 3 days later after birth. The median cord and infant BNP levels were similar in vaginal and cesarean delivery. There was no difference between the median cord and infant BNP levels in vaginal deliveries [54.0 pg/ml (q1-q3: 40.0-111.5) and 66.0 pg/ml (q1-q3: 43.0-90.0) respectively, p=0.619]. However, the median infant BNP level was statistically significantly higher than the median cord BNP level [56.0 pg/ml (q1-q3: 39.0-84.0) and 75.0 pg/ml (q1-q3: 54.0-145.0), p=0.027] in cesarean deliveries. Uncomplicated vaginal deliveries were not associated with high BNP levels and thus fetal cardiac distress. Increased levels of BNP levels on the 3rd day in elective cesarean deliveries may be predictive of delayed postnatal pulmonary and cardiac adaptation.

The Atrial Natriuretic Peptide-to-brain Natriuretic Peptide Ratio Predicts Left Atrial Reverse Remodeling after Rhythm Control Therapy in Patients with Persistent Atrial Fibrillation.

Objective The association between natriuretic peptide levels in atrial fibrillation (AF) patients with advanced left atrial (LA) remodeling and reverse remodeling after rhythm control therapy has not been clarified. The present study assessed the role of atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) measurements to predict LA reverse remodeling after catheter ablation (CA) in persistent AF patients with LA enlargement. Methods This study included 88 persistent AF patients with LA enlargement (volume index >48 mL/m2) who underwent CA. Plasma ANP and BNP levels were analyzed before CA in all patients. The study population was divided into 2 groups according to the extent of decrease in the LA volume index (LAVI) at 6 months after CA: responders were those with a ≥15% reduction in the LAVI, and all others were non-responders. Results At follow-up, 58 patients (66%) were classified as responders. The preprocedural ANP level was significantly higher in the responders than in the non-responders (p=0.03). Furthermore, the ANP-to-BNP ratio (ANP/BNP) was significantly higher in the responders than in the non-responders (p<0.01). The ANP/BNP was correlated with the percentage decrease in the LAVI (r = 0.391, p<0.01). A multivariate linear regression analysis revealed that the ANP/BNP before CA was an independent predictor of LA reverse remodeling (p<0.01). Conclusions The preprocedural ANP/BNP was a robust predictor of reverse remodeling of the enlarged LA after sinus rhythm restoration by rhythm control therapy in persistent AF patients.

Impact of cardiac power output, invasively measured by right heart catheterization, on exercise capacity and clinical outcomes in patients with chronic heart failure

Abstract Background Cardiac power output (CPO) is a novel hemodynamics parameter that is derived from both flow and pressure, and therefore it represents the cardiac pumping ability. CPO is strongly associated with outcomes in patients with cardiogenic shock. Nevertheless, less data is available about the impact of CPO on exercise capacity or clinical outcomes in patients with chronic heart failure (CHF). Purpose The present study aimed to investigate the impact of CPO on exercise intolerance or morbidity and mortality in patients with CHF who underwent invasive right heart catheterization. Methods The study enrolled 280 consecutive patients with CHF who underwent cardiopulmonary exercise testing and right heart catheterization between 2013 and 2018. The primary outcome was composite of heart failure hospitalization and death. CPO was calculated as (mean arterial pressure × cardiac output [CO])/451. Study population was divided into 2 groups according to the established cut-off value of CPO (= 0.53 W). Results Patients with low CPO (n = 99) were older and lower body mass index and displayed poorer kidney function, higher plasma brain natriuretic peptide (BNP) levels and lower left ventricular ejection fraction (LVEF) as compared to patients with high CPO (n = 181). CPO was correlated with peak oxygen consumption (Peak V̇O2), peak workload achievement, and ventilatory efficiency (V̇E/V̇CO2 slope) (Figure 1), while each of CO or mean arterial pressure was not. There were 48 patients with events over a median follow-up period of 3.5 (Interquartile range 1.0-6.0) years. Patients with low CPO had a 2.0-fold higher risk of events as compared to those with high CPO (HR 1.97; 95%CI, 1.12-3.48, P = 0.02, Figure 2). In multivariable Cox regression, 0.1-decreased in CPO was associated with 19% increased adverse events even after adjustment for gender, BNP, renal function, LVEF, and pulmonary capillary wedge pressure (HR 0.81; 95%CI, 0.67-0.99, P = 0.04). Conclusions CPO was associated with reduced exercise capacity and poor clinical outcomes, suggesting that CPO is useful for risk stratification in patients with CHF. Further study is required to identify therapies targeting CPO to improve the exercise capacity or clinical outcomes in patients with CHF.Figure1Figure2

Abstract 11601: Does Artificial Intelligence Dream of Elevated Natriuretic Peptide in Chest Radiography?

Introduction: Heart failure pandemic is a medical issue, and its diagnosis can be challenging. Hypothesis: To assess the hypothesis that the artificial intelligence (AI) model for predicting elevated brain natriuretic peptide (BNP) levels from chest X-ray images has sufficient performance and could improve the diagnostic performance of human. Methods: Patients who underwent chest radiography and BNP testing on the same day were enrolled in this study. The chest X-ray images were labeled based on plasma BNP levels &gt;= 200 pg/mL. We trained models that predicted the label, and the final ensemble model was constructed. Humans were trained and tested to predict labels, followed by the same test, referring to the prediction of the AI model. Diagnostic performance was assessed. Results: Among the 1607 patients, 10103 chest X-ray images and BNP values were collected. We assembled 31 models as the final model with an accuracy of 0.855, precision of 0.873, recall of 0.827, receiver-operating-characteristics area-under-curve (AUC) of 0.929, and precision-recall AUC of 0.934. The accuracy of the testing by 35 individuals significantly improved from 0.708±0.049 to 0.829±0.069 (P &amp;lt; 0.001) with AI assistance. The accuracy of the experts was higher than that of non-experts (0.692±0.042 vs. 0.728±0.051, P = 0.030); however, with the AI assistance, the accuracy of the non-experts was rather higher than that of the experts (0.851±0.074 vs. 0.803±0.054, P = 0.033). Conclusions: The AI model can predict elevated BNP levels from chest X-ray images and could improve the diagnostic performance of humans.

Abstract 13434: Prognostic Impact of Functional Limitations in Acute Decompensated Heart Failure Patients With Reduced &amp; Preserved Left Ventricular Ejection Fraction

Background: Although functional limitations (FL) could predict clinical status in patients with heart failure (HF), these clinical significances have not been fully elucidated. Hypothesis: Severe FL would be associated with poor prognosis both in patients with HFrEF and HFpEF. Aims: The purpose of this study was to examine the prognostic significance of FL in patients with acute decompensated heart failure (ADHF), relating to left ventricular ejection fraction (LVEF). Methods: We studied 340 patients admitted for ADHF in our prospective cohort study (Osaka Prefectural Acute heart failure Registry: OPAR study)(HFrEF[LVEF≤50%]:n=175 and HFpEF[LVEF&gt;50%]:n=165). Clinical data, echocardiography and venous blood sampling were performed just before discharge. FL were evaluated using the Performance Measure for Activities of Daily Living-8 (PMADL-8 ranges 8-32, and higher scores indicate worse FL). The endpoint was the composite of worsening heart failure rehospitalization and cardiac death. Results: During a follow up period of 3.0±1.9 years, 123 patients (64 patients in HFrEF and 59 patients in HFpEF) reached the primary endpoint. PMADL-8 was significantly smaller in patients with HFrEF than HFpEF (18.9±7.1 vs 21.0±6.1, p=0.004). On multivariate Cox analysis, PMADL-8 score was an independent risk factor for the primary endpoint both in HFrEF and HFpEF after adjustment for major confounders (age, sex, systolic blood pressure, and plasma brain natriuretic peptide level). Patients with high PMADL-8 scores had a higher risk of the primary endpoint than those with low PMADL-8 scores both in HFrEF (≥16 defined by ROC analysis, AUC 0.590[0.503-0.676]; adjusted hazard ratio: 2.20 [95%CI 1.08-4.48], 43% vs 25%, p=0.03) and HFpEF (≥25 defined by ROC analysis, AUC 0.617 [0.528-0.707]; adjusted hazard ratio: 1.95 [95%CI 1.04-3.66], 50% vs 29%, p=0.04). Conclusion: FL evaluated based on PMADL-8 was associated with poor prognosis in ADHF patients with both HFrEF and HFpEF.

Abstract 13419: Transient Coronary Artery to Left Ventricular Fistula With Diastolic Mitral Regurgitation

Introduction: A fistula from a coronary artery to the cardiac chamber is incidentally found in 0.08% to 0.3% of patients undergoing coronary angiography. Case Presentation: A 73-year-old woman with hypertension, diabetes mellitus, chronic renal failure, and nephrosis visited our department due to dyspnea. The patient’s physical examination revealed a blood pressure of 191/109 mmHg and a pulse rate of 77 beats per min. The blood sampling results revealed a plasma brain natriuretic peptide level of 2,001 pg/mL. A 12-lead electrocardiogram showed poor R wave progression in leads V1 to V4. Chest radiography revealed left pleural effusion. Parasternal transthoracic echocardiography showed left ventricular hypertrophy. Left ventricular (LV) ejection fraction was 41%. A pulsed-wave Doppler echocardiography at the mitral inflow showed diastolic mitral regurgitation and a fusion of E and A waves. An unusual myocardial flow was noted in the apical myocardium. It was directed toward the apical surface during systole (Fig. 1a), and directed toward the LV lumen during diastole (Fig. 1b), suggesting coronary artery to LV fistula through sinusoid. Global strain obtained from apical long axis imaging showed myocardial shortening continued to diastole, suggesting post-systolic shortening (PSS). After treatment for hypertension, both of myocardial flow and diastolic MR disappeared. A longitudinal global strain imaging revealed disappearance of PSS. Conclusion: This is a rare case of diastolic MR due to PSS at the fistula from the coronary artery to the left ventricle.

Comparative observation of changes in natriuretic peptides before and after interventional therapy for congenital heart disease

OBJECTIVE: To explore changes in the plasma atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) in patients with left-to-right shunt congenital heart disease (CHD) before and in the early stage after interventional occlusion and to evaluate the clinical significance. METHODS: Among 97 patients with left-to-right shunt CHD undergoing interventional occlusion, 34 cases had a VSD (ventricular septal defect), 35 cases had an ASD (atrial septal defect), and 28 cases had PDA (patent ductus arteriosus). Another 20 normal adults formed the control group. An ELISA was used to determine the plasma ANP and BNP levels before and on the third day after the operation to evaluate their correlations with cardiac functions and the defect size. RESULTS: The plasma ANP and BNP levels of patients with left-to-right shunt CHD were increased compared with those of the normal control group (P&lt; 0.01), and the plasma ANP and BNP levels were decreased on the third day after interventional occlusion compared with the preoperative levels (P&lt; 0.05). The plasma ANP and BNP levels were correlated with the New York Heart Association (NYHA) grade, left ventricular ejection fraction and defect diameter (P&lt; 0.05). CONCLUSION: Patients with left-to-right congenital heart disease exhibit activation of ANP and BNP, which can be alleviated in the early stage after intervention occlusion. Left-to-right shunt congenital heart disease is given priority over atrial septal defect (ASD), ventricular septal defect (VSD) and patent ductus arteriosus (PDA). Early traditional methods included repair or correction by open heart surgery under extracorporeal circulation (also known as cardiopulmonary bypass, CPB). However, interventional therapy has become a developing trend for the treatment of congenital heart disease since 1967, when Porstmann et al. [1]. reported the transcatheter closure of ASD for the first time. The application of the AMPLATZER occluder, which is a simple and feasible method, has improved the safety of the treatment and enabled the therapeutic effect to reach ideal levels. The natriuretic peptide (NP) family consists of the atrial natriuretic polypeptide (ANP), the brain natriuretic peptide, which is also known as the B type natriuretic peptide (BNP), the C type natriuretic peptide (CNP), the renal natriuretic peptide (RNP) and the D type natriuretic peptide (DNP). These family members are similar in structure, have strong natriuretic, diuretic and vasodilative effects and antagonize the activity of the renin-angiotensin-aldosterone system (RAAS) and the sympathetic nerve. Together, the natriuretic peptides sensitively and specifically reflect the ventricular function state. Although all types of congenital heart disease differ in anatomical structure, they all contain the common features of heart failure. This study detected changes in the serum ANP and BNP levels in patients with left-to-right shunt congenital heart disease before and on the third day after interventional occlusion to evaluate the early changes in left-to-right shunt congenital heart disease after interventional occlusion through neuroendocrine.

The impact of COVID-19 on BNP, NT-proBNP and ANP in heart failure.

Extensive research has been conducted on biomarkers associated with coronavirus disease 2019 (COVID-19) in both healthy individuals and those with various conditions, particularly heart diseases. However, there is a limited investigation into the relationship between widely used cardiac biomarkers known as natriuretic peptides, including Brain natriuretic peptide (BNP), N-Terminal Pro-B-Type Natriuretic Peptide (NT-proBNP), and Atrial natriuretic peptide (ANP), and COVID-19 infection specifically in patients with heart failure. These natriuretic peptides assess the hemodynamic stress on the heart wall and have the potential to serve as biomarkers for evaluating the severity of COVID-19 infection in heart failure patients. Therefore, this study aimed to assess the plasma concentration of BNP, NT-proBNP, and ANP in a medium-sized cross-sectional case-control study involving 360 heart failure patients, both infected and uninfected with COVID-19. The heart failure patients were categorized into subgroups based on their Ejection Fraction (EF) percentage, namely heart failure with reduced EF (HFrEF), heart failure with mid-range EF (HFmrEF), and heart failure with preserved EF (HFpEF). Our findings demonstrate a significant increase in plasma levels of BNP and NT-proBNP in all heart failure patients, as well as in each subgroup (HFrEF, HFmrEF, and HFpEF) when infected with COVID-19, compared to uninfected heart failure patients. These established cardiac biomarkers have the potential to be utilized as future indicators for assessing the severity of COVID-19 infection in heart failure patients, thereby enhancing heart failure management and reducing irreversible cardiac damage.

Diagnostic yield and predictive value on left ventricular remodelling of genetic testing in dilated cardiomyopathy.

We assessed the diagnostic yield of genetic testing and the relationship of left ventricular (LV) reverse remodelling (LVRR) with the presence of DNA pathogenic (P) or likely pathogenic (LP) variants in patients with dilated cardiomyopathy (DCM). From 680 outpatients followed at the Heart Failure Outpatient Clinic of our institution, we selected subjects with a diagnosis of DCM as defined by LV ejection fraction (LVEF) ≤40% and LV dilatation not explained by coronary artery disease or other causes. All patients were offered genetic investigation of 42 disease-associated DCM genes with next-generation sequencing. Seventy patients fulfilled the definition of DCM and 66 underwent genetic investigation. We identified 18 P/LP variants in 16 patients, with a diagnostic yield of 24%. The most common variants were truncating TTN variants (n=7), followed by LMNA (n=3), cytoskeleton Z-disc (n=3), ion channel (n=2), motor sarcomeric (n=2), and desmosomal (n=1) genes. After a median follow-up of 53months (inter-quartile range 20-111), patients without P/LP variants exhibited higher systolic and diastolic blood pressure, lower plasma brain natriuretic peptide levels, and a larger extent of LVRR, as reflected by the increase in LVEF (+14% vs. +1%, P=0.0008) and decrease in indexed LV end-diastolic diameter (-6.5 vs. -2mm/m2 , P=0.03) compared with patients with P/LP variants. Our results confirm the high diagnostic yield of genetic testing in selected DCM patients and suggest that identification of P/LP variants in DCM portends poorer LVRR in response to guideline-directed medical therapy.

USEFULNESS OF BPN LEVELS IN IDENTIFYING DIABETIC HYPERTENSIVES WITH SYSTOLIC-DIASTOLIC LEFT VENTRICULAR DYSFUNCTION. ABILITY OF THE ANGIOTENSIN II INHIBITOR TO CONVERT IT BACK

Objective: We tested the hypothesis that the renin-angiotensin system could convert left ventricular diastolic dysfunction in patients with type 2 diabetes. Design and method: Fifty asymptomatic patients with type 2 diabetes were recruited in this double-blind cross-over trial. Baseline left ventricular diastolic function was assessed with Doppler echocardiography; using velocity ratios of peak flow through the mitral orifice (E/A) and the integral velocity of before end diastolic transmitral flow (VTIE/VTIA). In addition, plasma brain natriuretic peptide (BNP) levels were measured. Patients randomly received either zofenopril (15mg/day), or Olmesartan (10mg/day) or their combination for 3 months and each time after a 2-week washout period. Measurements were repeated at the end of each treatment period. Results: Both E/A and VTIE/VTIA ratios increased (29 and 20% with zofenopril, 25 and 23% with olmesartan, and 36 and 28% with combination treatment, respectively, p &lt; 0.001), while levels plasma BNP levels were significantly reduced with all 3 regimens (9% with zofenopril, 25% with olmesartan, and 36% with combination, p &lt; 0.001). Conclusions: Both olmesartan and zofenopril improve left ventricular diastolic echocardiographic indices and reduce plasma BNP levels in diabetic patients, their combination produces an even better therapeutic effect.

BNP protects against diabetic cardiomyopathy by promoting Opa1-mediated mitochondrial fusion via activating the PKG-STAT3 pathway

Brain natriuretic peptide (BNP) belongs to the family of natriuretic peptides, which are responsible for a wide range of actions. Diabetic cardiomyopathy (DCM) is often associated with increased BNP levels. This present research intends to explore the role of BNP in the development of DCM and the underlying mechanisms. Diabetes was induced in mice using streptozotocin (STZ). Primary neonatal cardiomyocytes were treated with high glucose. It was found that the levels of plasma BNP started to increase at 8 weeks after diabetes, which preceded the development of DCM. Addition of exogenous BNP promoted Opa1-mediated mitochondrial fusion, inhibited mitochondrial oxidative stress, preserved mitochondrial respiratory capacity and prevented the development of DCM, while knockdown of endogenous BNP exacerbated mitochondrial dysfunction and accelerated DCM. Opa1 knockdown attenuated the aforementioned protective action of BNP both in vivo and in vitro. BNP-induced mitochondrial fusion requires the activation of STAT3, which facilitated Opa1 transcription by binding to its promoter regions. PKG, a crucial signaling biomolecule in the BNP signaling pathway, interacted with STAT3 and induced its activation. Knockdown of NPRA (the receptor of BNP) or PKG blunted the promoting effect of BNP on STAT3 phosphorylation and Opa1-mediated mitochondrial fusion. The results of this study demonstrate for the first time that there is a rise in BNP during the early stages of DCM as a compensatory protection mechanism. BNP is a novel mitochondrial fusion activator in protecting against hyperglycemia-induced mitochondrial oxidative injury and DCM through the activation of NPRA-PKG-STAT3-Opa1 signaling pathway.

Controlling nutritional status score predicts 2-year outcomes in elderly patients admitted for acute heart failure

BackgroundHeart failure (HF) is a major cause of death among the elderly. Its prevalence increases dramatically with age. The prevalence of malnourished subjects is high in hospitalized elderly patients. We aimed to investigate the prognostic role of malnutrition, assessed by controlling nutritional status (CONUT) score, on adverse clinical outcomes in the elderly admitted for acute HF.MethodsWe enrolled 293 patients (mean age 84 years; 48% men) consecutively admitted for acute HF to the Internal Medicine or Geriatrics Divisions at the ‘IRCCS Sacro Cuore-Don Calabria’ Hospital of Negrar (Verona, Italy) from 2013 to 2015. We predicted the risk of all-cause death, re-hospitalizations for HF and non-HF causes, and the composite of all-cause death or hospitalizations over 2-year follow-up. Patients were divided into four groups according to CONUT score: normal-CONUT (0–1; n = 30); mild-CONUT (2–3; n = 56); moderate-CONUT (4–7; n = 171); and severe-CONUT (≥ 8; n = 36).ResultsHigher CONUT scores were associated with older age and lower entry blood pressures. No difference in hemodynamics was noted at the discharge. Kaplan–Meier curves showed a significant association between worsening CONUT scores and risk of all-cause death (p < 0.01), re-hospitalizations (p < 0.01), or both (p < 0.001). Cox regression analysis revealed these significant associations persisted after adjustment for age, sex, pre-existing cardiovascular disease, diabetes, chronic kidney disease, heart rate, systolic blood pressure, and plasma brain natriuretic peptide levels at discharge (all-cause mortality HR = 1.29 (1.00–1.66), p = 0.049; hospitalization for HF HR = 1.36 (1.03–1.81), p = 0.033; hospitalization for non-HF HR = 1.38 (1.03–1.86), p = 0.034; composite outcome HR = 1.33 (1.07–1.64), p = 0.01).ConclusionsMalnutrition, assessed by the CONUT score, is common among elderly patients admitted for acute HF and is strongly related to increased long-term risk of all-cause death and re-hospitalizations.

The Effect of Balloon Mitral Valvuplasty on BNP Plasma Level in Mitral Stenosis

Background: Mitral valve stenosis (MS), which could be progressive, is one of the most important valvular disorders in developing countries. Percutaneous transvenous mitral commissurotomy (PTMC) is a well-accepted treatment option for dealing with symptomatic MS. Brain natriuretic peptide (BNP) has been used as a prognostic marker for clinical outcomes in patients with heart failure and acute coronary syndrome routinely. Objectives: This study aimed to determine the relationship between BNP levels and hemodynamic parameters in patients with MS who underwent PTMC. Methods: In this case-control study, 90 patients with severe isolated rheumatic mitral stenosis and undergoing PTMC were enrolled. In the study group, BNP levels were measured by performing radioimmunoassay on all participants 30 minutes before PTMC and 24 hours after PTMC. Data were analyzed using SPSS, and P-value &lt; 0.05 was considered significant. Results: Fifty patients with MS who underwent PTMC were included in this study. The level of BNP before PTMC was 473.78 ± 66.95 pg/dL in patients with MS. The level of BNP in patients after PTMC reached 341.54 ± 48.3 pg/dL, which was indicative of a significant reduction in the level of BNP after PTMC (P-value = 0.006). Conclusions: A considerable decline was observed in the serum level of BNP following a successful PTMC, which was indicative of an improvement in clinical and hemodynamic status; hence, it was reasonably suggested that the serum level of BNP was effective in evaluating the response from patient with severe MS to PTMC.

S-20-3: PLASMA ATRIAL AND BRAIN NATRIURETIC PEPTIDES LEVELS AND THE RISK OF INCIDENT ATRIAL FIBRILLATION: THE SUITA STUDY

Background: Atrial fibrillation (AF), a common cardiac rhythm abnormality, is associated with significantly increased morbidity and mortality risk. We developed the risk prediction of incident AF using traditional risk factors. It is essential to consider the residual risk to increase risk predictions. Heart failure is not a factor that appeared in the Suita AF score but others. There is no prospective study on the relationship between plasma atrial and brain natriuretic peptide (ANP and BNP) levels and incident AF in non-Western residents. Objectives: We hypothesized the association between ANP, BNP, and incident AF in the Suita Study. Methods: A total of 2,828 participants (mean age 66.7 ± 10.4 years without AF at the baseline) have been prospectively followed-up for incident AF since November 2005. AF was diagnosed when AF or atrial flutter was present on ECG at a biannual health examination or when AF was indicated as a current illness or was in the medical records during follow-up. ANP and BNP were measured by the CLEIA methods at the baseline survey examination. Cox proportional hazard ratios (HRs) and 95% confidence intervals (CIs) were analysed after adjusting for the risk components of the recently published Suita AF risk score. Statistical analyses were performed using Cox proportional hazards regression methods and evaluated using C statistics and net reclassification improvement. Results: The baseline prevalence of hypertension according to the BNP levels were 34.5%, 50.1%, and 78.8% in BNP &lt; 18.5 pg/dL, 18.5–99 pg/dL, and P ≧ 4100 pg/dL, respectively. During the 16,584 person-years of follow-up, we observed 65 incidents of AF. Compared to the subjects with ANP&lt; 42 pg/dL and BNP&lt; 18.4 pg/dL, the adjusted HRs (95% confidence intervals) of incident AF were 2.70 (1.53–4.78) for the subjects with ANP ≧ 42 pg/dL and 2.09 (1.09–4.01) and 9.75 (3.82–24.87) for the subjects with BNP = 18.5–99 pg/dL and BNPP ≧ 4100 pg/dL, respectively. The addition of ANP and BNP to variables recently combined in the Suita AF risk score showed an integrated discrimination improvement of 0.061 (0.035–0.087) and 0.068 (0.036–0.100), with 13.3% and 19.1% relative improvement in reclassification analysis, respectively. Furthermore, the addition of ANP to the Suita AF score with BNP showed a significant but slight integrated discrimination improvement of 0.007 (0.001–0.012) (P = 0.01). Conclusions: Each elevated ANP and BNP contributed significantly to the predictive for incident AF to calculate the Suita Risk Score, but adding ANP to the Suita AF score with BNP improved the risk prediction slightly.

Cardio-Ankle Vascular Index Reflects the Efficacy of Waon Therapy in Heart Failure Patients.

Waon therapy is a form of thermal treatment in a dry sauna developed by Tei. Although Waon therapy is reportedly effective for chronic heart failure (CHF) patients, not all patients respond to the therapy. The reason for this ineffectiveness has not been fully clarified. The cardio-ankle vascular index (CAVI) is an index of arterial stiffness of the arterial tree from the origin of the aorta to the ankle, and it is thought to reflect some of the afterload of the left ventricle. We investigated the effects of Waon therapy on CAVI and plasma brain natriuretic peptide (BNP) level to clarify the usefulness of CAVI during Waon therapy.CHF patients (n = 21) treated with Waon therapy (2 weeks of 10 sessions) were divided into two groups: responders with an improved BNP level (n = 11) and nonresponders with no improvement in BNP (n = 10). CAVI was measured using Vasela 1500.A significant decrease in CAVI (median and interquartile range) was observed in the responder group (from 10.3 [9.6, 11.6] to 9.6 [8.6, 10.3], P = 0.021), whereas no change was observed in the nonresponder group (from 9.6 [8.6, 10.5] to 9.5 [9.1, 11.2], P = 0.919). The incidence of rehospitalization or cardiac death due to heart failure was significantly higher in patients in whom Waon therapy was ineffective at 12 months of follow-up (log-rank P = 0.001).The effectiveness of Waon therapy in CHF patients may be reflected by the improvement in CAVI.

Focused ultrasound stimulation of the inflammatory reflex at the spleen ameliorates pulmonary arterial hypertension in rodents

Abstract Background Inflammation is a major contributor in pulmonary arterial hypertension (PAH) pathogenesis. Non-invasive, focused ultrasound stimulation (FUS) of the spleen activates the neuroimmune inflammatory reflex (IR) and suppresses systemic inflammation [1]. Purpose We aimed to explore whether daily FUS of the spleen improves haemodynamics and biomarkers by modulating the IR, in a rat model of PAH. Methods Sprague-Dawley rats (n=12) were injected s.c. with Sugen5416 (VEGF receptor inhibitor) and then, were placed in a hypoxic chamber (FiO2=10%) for 21 days, followed by 14 days of re-exposure to normoxia (FiO2=10%). At day 21, rats were randomized to either FUS (n=6) or sham-stimulation of the spleen (n=6). Each FUS- or sham-stimulation session consisted of 12 minutes. After 14 days of treatment, in a terminal experiment, right ventricular systolic pressure (RVSP) and arterial pressure were measured invasively, as well as biomarkers, in each animal (Figure 1A). Results FUS significantly reduced RVSP compared with the sham-stimulation (Mean±SEM, 50.83±3.57 mmHg vs 72.50±5.81; p=0.009), resulting in a 30% relative reduction (Figure 1B). Mean systemic arterial pressure was similar in the 2 groups (Mean±SEM, 79.83±3.73 mmHg vs. 87.00±2.95; p=0.137) (Figure 1C), as was the change in heart rate between day 1 and day 14 of treatment period (−19.53±5.36% vs. −16.79±3.1, p=0.61) (Figure 1D). Consistently, plasma brain natriuretic peptide (BNP) levels are reduced in the FUS group (119.45±19.93 ng/μl vs. 319.39±91.85; p=0.019), indicative of reduced myocardial wall stress in the FUS group (Figure 1E). Conclusion Non-invasive FUS of the spleen reduced RVSP by ∼30% and BNP without significantly affecting systemic pressure or heart rate, in rats with severe PAH. Non-invasive FUS, by modulating the IR, may exert an anti-inflammatory effect in PAH. FUS of the spleen is noninvasive, safe, widely available and easy to perform, and should be further explored as a possible therapeutic option in PAH. Funding Acknowledgement Type of funding sources: Private hospital(s). Main funding source(s): Northwell Health

Effects of high-absorption curcumin for the prevention of hypertensive heart disease: a double-blind, placebo-controlled, randomized clinical study.

AimsHypertension is a strong risk factor for heart failure with preserved ejection fraction. Curcumin has p300-specific histone acetyltransferase inhibitory activity, suppresses cardiomyocyte hypertrophy and fibrosis, and significantly reduces myocardial brain natriuretic peptide (BNP) expression without altering blood pressure in a rat model of hypertensive heart disease. This double-blind, placebo-controlled, randomized study, for the first time, aimed to examine the efficacy of a high-absorption curcumin for the prevention of hypertensive heart disease in humans.Methods and resultsPatients exhibiting initial signs of hypertensive heart disease with left ventricular ejection fraction ≥60% and stable blood pressure <140/90 mmHg orally took a double-blinded capsule (either a 90 mg curcumin capsule or placebo) twice daily for 24 weeks. The primary endpoint was per cent changes in left ventricular diastolic function (E/E′) from baseline to 6 months after administration. The secondary endpoint was the per cent change in plasma BNP levels. The E/E′ ratio per cent change from baseline to 6 months after administration was similar between the placebo (n = 69) and the curcumin (n = 73) groups. The per cent change in plasma BNP levels was significantly lower in the curcumin group than in the placebo group. In patients <65 years, BNP per cent changes were significantly lower in the curcumin group than in the placebo group, but similar between groups in ≥65 years (<65 vs. ≥65 years: P for interaction = 0.011).ConclusionsA high-absorption curcumin agent did not affect the E/E′ ratio, rather it significantly inhibited the increase in plasma BNP levels in patients with initial signs of hypertensive heart disease.

Levels of Serum IGF-1, HCY, and Plasma BNP in Patients with Chronic Congestive Heart Failure and Their Relationship with Cardiac Function and Short-Term Prognosis.

Objective To investigate the levels of serum insulin like growth factor-1 (IGF-1), homocysteine (HCY), and plasma brain natriuretic peptide (BNP) in patients with chronic congestive heart failure (CCHF) and their relationship with cardiac function and short-term prognosis. Methods A total of 95 patients with CCHF admitted to our hospital from October 2017 to December 2018 were selected as the observation group. Patients conform to grade II∼IV of the New York Heart Association (NYHA) heart function class. At the same time, the people with normal physical examination results were selected as a control group. Serum IGF-1, HCY, and plasma BNP levels were detected in the two groups, and left ventricular end-diastolic diameter (LVDd) and left ventricular ejection fraction (LVEF) were detected in the observation group. According to the follow-up results, the observation group was divided into the subgroup with good prognosis and the subgroup with poor prognosis. The relationship between the levels of serum IGF-1, HCY, and plasma BNP among cardiac function and short-term prognosis were analyzed. Results The serum IGF-1 level of the observation group was lower than that of the control group, and the serum HCY and plasma BNP levels were higher than those of the control group (P < 0.05). Serum IGF-1 level in grade III of NYHA was lower than that in grade II, and serum HCY and plasma BNP levels were higher than those in grade II. Serum IGF-1 level in grade IV was lower than that in grade II and grade III, and serum HCY and plasma BNP levels were higher than those in grade II and grade III (P < 0.05). Serum IGF-1 level was negatively correlated with LVDd and positively correlated with LVEF. Serum HCY and plasma BNP levels were positively correlated with LVDd and negatively correlated with LVEF (P < 0.05). There were 42 patients with poor prognoses (44.21%). Serum IGF-1 levels of patients with poor prognosis were lower than those with good prognosis, and serum HCY and plasma BNP levels were higher than those with good prognosis (P < 0.05). Conclusion The serum IGF-1 level in patients with CCHF decreased, and serum HCY and plasma BNP levels increased. Serum IGF-1, HCY, and plasma BNP were correlated with cardiac function and have some clinical value for short-term prognosis.

B-Type Natriuretic Peptide (BNP) Revisited—Is BNP Still a Biomarker for Heart Failure in the Angiotensin Receptor/Neprilysin Inhibitor Era?

Simple SummaryActive BNP-32, less active proBNP-108, and inactive N-terminal proBNP-76 all circulate in the blood. The circulating protease neprilysin has lower substrate specificity for BNP than ANP, while proBNP and N-terminal proBNP are not degraded by neprilysin. Currently available BNP immunoassays react with both mature BNP and proBNP; therefore, measured plasma BNP is mature BNP + proBNP. Because ARNI administration increases mature BNP, measured plasma BNP initially increases with ARNI administration by the amount of the increase in mature BNP. Later, ARNI administration reduces myocardial wall stress, and the resultant reduction in BNP production more than offsets the increase of mature BNP due to inhibition of degradation by neprilysin, resulting in lower plasma BNP levels. In the ARNI era, BNP remains a useful biomarker for heart failure, though mild increases early during ARNI administration should be taken into consideration.Myocardial wall stress, cytokines, hormones, and ischemia all stimulate B-type (or brain) natriuretic peptide (BNP) gene expression. Within the myocardium, ProBNP-108, a BNP precursor, undergoes glycosylation, after which a portion is cleaved by furin into mature BNP-32 and N-terminal proBNP-76, depending on the glycosylation status. As a result, active BNP, less active proBNP, and inactive N-terminal proBNP all circulate in the blood. There are three major pathways for BNP clearance: (1) cellular internalization via natriuretic peptide receptor (NPR)-A and NPR-C; (2) degradation by proteases in the blood, including neprilysin, dipeptidyl-peptidase-IV, insulin degrading enzyme, etc.; and (3) excretion in the urine. Because neprilysin has lower substrate specificity for BNP than atrial natriuretic peptide (ANP), the increase in plasma BNP after angiotensin receptor neprilysin inhibitor (ARNI) administration is much smaller than the increase in plasma ANP. Currently available BNP immunoassays react with both mature BNP and proBNP. Therefore, BNP measured with an immunoassay is mature BNP + proBNP. ARNI administration increases mature BNP but not proBNP, as the latter is not degraded by neprilysin. Consequently, measured plasma BNP initially increases with ARNI administration by the amount of the increase in mature BNP. Later, ARNI reduces myocardial wall stress, and the resultant reduction in BNP production more than offsets the increase in mature BNP mediated by inhibiting degradation by neprilysin, which lowers plasma BNP levels. These results suggest that even in the ARNI era, BNP can be used for diagnosis and assessment of the pathophysiology and prognosis of heart failure, though the mild increases early during ARNI administration should be taken into consideration.

Systolic Pulmonary Artery Pressure and Cardiovascular Biomarkers—New Non-Invasive Ways to Detect Pulmonary Hypertension in Patients with Severe Aortic Valve Stenosis Undergoing TAVR?

Background: Patients with severe aortic valve stenosis (AS) frequently present with pulmonary hypertension (PH). The gold standard for detection of pulmonary hypertension is right heart catheterization, which is not routinely performed as a preoperative standard in cardiology centers today, neither before surgical valve replacement nor before transcatheter aortic valve replacement (TAVR) procedure. Echocardiographic determination of systolic pulmonary artery pressure (sPAP) provides an opportunity to assess the presence or absence of PH. The aim of the present study was to investigate the extent to which plasma levels of common cardiovascular biomarkers behave in patients with severe AS and an sPAP &lt;40 mmHg in comparison to patients with an sPAP ≥40 mmHg. Methods: 179 patients with echocardiographic evidence of severe AS before TAVR procedure were divided into 2 groups based on sPAP. An sPAP of 40 mmHg was considered the cut-off value, with absence of PH defined by an sPAP &lt;40 mmHg (n = 82) and presence of PH defined by an sPAP ≥40 mmHg (n = 97). Directly before TAVR, a blood sample was drawn from each patient, and plasma concentrations of the cardiovascular biomarkers Soluble Suppression of Tumorigenicity-2 (sST2), Growth/Differentiation of Factor-15 (GDF-15), Heart-Type Fatty-Acid Binding Protein (H-FABP), Insulin Like Growth Factor Binding Protein 2 (IGF-BP2), Soluble Urokinase-Type Plasminogen Activator Receptor (suPAR), Brain Natriuretic Peptide (BNP) and Cardiac Troponin I (cTnI) were determined. Results: Patients with an sPAP ≥40 mmHg had significantly higher sST2 (p = 0.010), GDF-15 (p = 0.005), IGF-BP2 (p = 0.029), suPAR (p = 0.018), BNP (p &lt; 0.001) and cTnI (p = 0.039) plasma levels. Only for H-FABP (p = 0.069), no significant differences were discernible between the two groups. In addition, cut-off values were calculated to predict an sPAP ≥40 mmHg. Significant results were shown with 16045.84 pg/mL for sST2 (p = 0.010), with 1117.54 pg/mL for GDF-15 (p = 0.005), with 107028.43 pg/mL for IGF-BP2 (p = 0.029), with 3782.84 pg/mL for suPAR (p = 0.018), with 2248.00 pg/mL for BNP (p &lt; 0.001) and with 20.50 pg/mL for cTnI (p = 0.002). Conclusions: sPAP as an echocardiographic parameter in combination with supplementary use of cardiovascular biomarkers presented here have the potential to provide more detailed information about the presence or absence of PH in a non-invasive way.