Brain Natriuretic Peptide Levels Research Articles

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 < 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.

Clinical characteristics and early prediction of mortality risk in patients with acute organophosphate poisoning-induced shock.

To further get insights of clinical characteristics of acute organophosphate poisoning-induced shock, investigate the relationship between shock and prognosis, and screen risk indicators for prognosis. A total of 73 patients with acute organophosphate poisoning admitted to our hospital between January 2014 and December 2021 were enrolled in this retrospective study. Patients were divided into the shock group and the non-shock group. The pH value of blood, arterial blood carbon dioxide partial pressure (PaCO2), arterial partial pressure of oxygen (PaO2), base excess (BE), lactic acid (Lac), serum albumin (ALB), total bilirubin (TBIL), alanine aminotransferase (ALT), serum creatinine (Cr), serum potassium (K), serum calcium (Ca), serum sodium (Na), blood chloride (Cl), serum troponin I (cTNI), brain natriuretic peptide (BNP), white blood cell count (WBC), hemoglobin (HGB), platelet count (PLT), and other clinical indicators of patients were recorded. Incidence of shock, time of shock onset, and outcomes of patients were also recorded. Cox proportional hazards regression models were performed for analysis. The incidence of organophosphate poisoning-induced shock was 30.1% (22/73), and 72.7% of shock patients developed shock blood pressure within 6 h. The levels of blood lactate, ALT, Cr, cTNI, BNP, and Cl in the shock group were significantly higher than those in the non-shock group, while the level of Ca and pH value was significantly lower than that in the non-shock group (all p < 0.05). Moreover, compared with patients without shock (2.0%), the mortality rate was significantly increased in patients with shock (36.4%), which was supported by the results from adjusted Cox proportional hazards regression model. We found that shock and elevated serum creatinine were associated with increased risk of death in patients with organophosphate poisoning (shock: HR, 10.9; 95% CI 1.2-96.3; elevated serum creatinine: HR, 1.0, 95% CI 1.0-1.0). This study indicated the association between elevated serum creatinine and increased mortality rates in patients with organophosphate poisoning, highlighting the importance of the comprehensive management of shock, especially the control of renal function, in these poisoning patients.

Predictors and impact of postoperative atrial fibrillation following thoracic surgery: a state-of-the-art review.

This review of 19 studies (39,783 patients) of atrial fibrillation after thoracic surgery addresses the pathophysiology, incidence, and consequences of atrial fibrillation in this population, as well as its prevention and management. Interestingly, atrial fibrillation was most often identified in patients not previously known to have the disease. Rhythm control with amiodarone was the most commonly used treatment and nearly all patients were discharged in sinus rhythm. Major predictors were age; male sex; history of atrial fibrillation; congestive heart failure; left atrial enlargement; elevated brain natriuretic peptide level; and the invasiveness of procedures. Overall, patients with atrial fibrillation stayed 3 days longer in hospital. We also discuss the importance of standardising research on this subject and provide recommendations that might mitigate the impact postoperative atrial fibrillation on hospital resources.

Effect of Pomegranate Extract On N-Terminal Pro Brain Natriuretic Peptide and Asymmetric Dimetylarginine Levels in Children with Pulmonary Artery Hypertension in Acyanotic Congenital Heart Disease

Background: Pulmonary arterial hypertension (PAH) is one of the complications due to acyanotic congenital heart disease. New treatment approach using natural ingredients from plants has been demonstrated in vitro to prevent and improve vascular remodeling in PAH. Objective: This study aimed to analyze the effect of pomegranate extract on N-terminal pro brain natriuretic peptide (NT pro BNP) and asymmetric dimethylarginine (ADMA) levels in children with PAH in acyanotic CHD. Method: This study is a double-blind, quasi-experimental text with pre-test, post-test, and control group approach to children aged one month to 10 years old in Outpatient Department of Pediatric Cardiology Department/Pediatrics Department RSUD Dr. Soetomo in the period of February-October 2022, alongside met the inclusion criteria. Data were analyzed using Wilcoxon and Mann-Whitney test with 95% CI. Result: The study cohort included 15 subjects in the placebo group and 15 subjects in pomegranate extract group. The study was predominantly female (53,3%) with a mean age of each group, i.e., placebo group was 49 months, and pomegranate extract group was 58 months. The mean level of NT pro-BNP in the pomegranate extract group was 29.31 ± 33.55 ng/L (p= 0.008) and its mean ADMA level was 5619 ± 6166 ng/L (p= 0.173). As for the difference of NT pro-BNP and ADMA level changes after the intervention did not show a significant difference (p-0,330; p=0,885, respectively). Conclusion: No significant effect towards NT pro- BNP and ADMA levels found with giving pomegranate extract to children with PAH due to acyanotic CHD.

Current Therapy and Liver Transplantation for Portopulmonary Hypertension in Japan.

Portopulmonary hypertension (PoPH) and hepatopulmonary syndrome are severe pulmonary complications associated with liver cirrhosis (LC) and portal hypertension. Three key pathways, involving endothelin, nitric oxide, and prostacyclin, have been identified in the development and progression of pulmonary arterial hypertension (PAH). To obtain a good effect with PAH-specific drugs in PoPH patients, it is important to diagnose PoPH at an early stage and promptly initiate therapy. The majority of therapeutic drugs are contraindicated for Child-Pugh grade C LC, and their effects decrease in the severe PAH stage. Among many LC patients, the measurement of serum brain natriuretic peptide levels might be useful for detecting PoPH. Previously, liver transplantation (LT) for PoPH was contraindicated; however, the indications for LT are changing and now take into account how well the PoPH is controlled by therapeutic drugs. In Japan, new registration criteria for deceased-donor LT have been established for PoPH patients. PoPH patients with a mean pulmonary arterial pressure &lt;35 mmHg and pulmonary vascular resistance &lt;400 dyn/s/cm-5 are indicated for LT, regardless of whether they are using therapeutic drugs. Combined with PAH-specific drugs, LT may lead to excellent long-term outcomes in PoPH patients. We aimed to review current therapies for PoPH, including LT.

A Story of PA/BSA and Biomarkers to Diagnose Pulmonary Hypertension in Patients with Severe Aortic Valve Stenosis-The Rise of IGF-BP2 and GDF-15.

(1) Background: Currently, echocardiography is the primary non-invasive diagnostic method used to screen patients with severe aortic valve stenosis (AS) for pulmonary hypertension (PH) by estimating systolic pulmonary artery pressure (sPAP). Other radiological methods have been a focus of research in the past couple of years, as it was shown that by determining the pulmonary artery (PA) diameter, prognostic statements concerning overall mortality could be made in these patients. This study compared established and novel cardiovascular biomarkers with the PA/BSA value to detect PH in patients with severe AS. (2) Methods: The study cohort comprised 188 patients with severe AS undergoing transcatheter aortic valve replacement (TAVR), who were then divided into two groups based on PA/BSA values obtained through CT-angiography. The presence of PH was defined as a PA/BSA ≥ 16.6 mm/m2 (n = 81), and absence as a PA/BSA < 16.6 mm/m2 (n = 107). Blood samples were taken before TAVR to assess cardiovascular biomarkers used in this study, namely brain natriuretic peptide (BNP), cardiac troponin I (cTnI), high-sensitive troponin (hsTN), soluble suppression of tumorigenesis-2 (sST2), growth/differentiation factor 15 (GDF-15), heart-type fatty acid-binding protein (H-FABP), insulin-like growth factor binding protein 2 (IGF-BP2), and soluble urokinase-type plasminogen activator receptor (suPAR). (3) Results: Patients with a PA/BSA ≥ 16.6 mm/m2 showed significantly higher levels of BNP (p = <0.001), GDF-15 (p = 0.040), and H-FABP (p = 0.007). The other investigated cardiovascular biomarkers did not significantly differ between the two groups. To predict a PA/BSA ≥ 16.6 mm/m2, cut-off values for the biomarkers were calculated. Here, GDF-15 (p = 0.029; cut-off 1172.0 pg/mL) and BNP (p < 0.001; cut-off 2194.0 pg/mL) showed significant results. Consequently, analyses of combined biomarkers were performed, which yielded IGF-BP2 + BNP (AUC = 0.721; 95%CI = 0.585−0.857; p = 0.004) as the best result of the two-way analyses and GDF-15 + IGF-BP2 + BNP (AUC = 0.727; 95%CI = 0.590−0.864; p = 0.004) as the best result of the three-way analyses. No significant difference regarding the 1-year survival between patients with PA/BSA < 16.6 mm/m2 and patients with PA/BSA ≥ 16.6 mm/m2 was found (log-rank test: p = 0.452). (4) Conclusions: Although PA/BSA aims to reduce the bias of the PA value caused by different body compositions and sizes, it is still a controversial parameter for diagnosing PH. Combining the parameter with different cardiovascular biomarkers did not lead to a significant increase in the diagnostic precision for detecting PH in patients with severe AS.

Adaptive capabilities of the cardiovascular system, taking into account regulation systems, in adolescents with juvenile idiopathic arthritis

Background. Juvenile idiopathic arthritis (JIA) is the most common rheumatological disease of childhood (1 : 1,000 children), which involves many organs and systems, primarily cardiovascular, with the gradual development of chronic heart failure. As you know, when the functional capacity of the heart decreases, a cascade of reactions of the neurohumoral regulation system is triggered and, first of all, the sympathoadrenal system is activated with an increase in the catecholamine production, the development of tachycardia. Due to this, the level of brain natriuretic peptide in the blood is increased. In children, chronic heart failure is asymptomatic. Therefore, determining tolerance to physical exertion plays an important role in its diagnosis. The purpose was to determine the functional state of the cardiovascular system and the tolerance to physical exertion in adolescents with JIA, taking into account the level of catecholamine excretion in the daily urine and the level of natriuretic peptide in the blood. Materials and methods. Fifty-six patients with JIA aged 12–17 years (13.28 ± 0.38 years) were examined. The control group consisted of 46 apparently healthy peers of the corresponding age. A heart ultrasound was performed to establish the functional state of the myocardium. To study tolerance to physical exertion, a six-minute walk test was performed with calculation of Kerdo index before and after the test. The level of catecholamine excretion in the urine and the level of natriuretic peptide in the blood were studied. Results. Patients with juvenile idiopathic arthritis had early signs of right ventricular myocardial systolic dysfunction (a decrease in the right ventricular ejection fraction). At the same time, we detected a decrease in the catecholamine level and an increase in the content of natriuretic peptide, which has a neuromodulatory effect at different levels of the sympathoadrenal system. Conclusions. Activation of the sympathetic division of the autonomic nervous system (increased Kerdo index) in patients with juvenile idiopathic arthritis does not ensure the effectiveness of minimal physical exertion in a six-minute walk test.

Waterpipe smoke inhalation potentiates cardiac oxidative stress, inflammation, mitochondrial dysfunction, apoptosis and autophagy in experimental hypertension

Cigarette smoking worsens the health of hypertensive patients. However, less is known about the actions and underlying mechanisms of waterpipe smoke (WPS) in hypertension. Therefore, we evaluated the effects of WPS inhalation in mice made hypertensive (HT) by infusing angiotensin II for six weeks. On day 14 of the infusion of angiotensin II or vehicle (normotensive; NT), mice were exposed either to air or WPS for four consecutive weeks. Each session was 30 min/day and 5 days/week. In NT mice, WPS increased systolic blood pressure (SBP) compared with NT air-exposed group. SBP increase was elevated in HT+WPS group versus either HT+air or NT+WPS. Similarly, the plasma levels of brain natriuretic peptide, C-reactive protein, 8-isoprostane and superoxide dismutase were increased in HT+WPS compared with either HT+air or NT+WPS. In the heart tissue, several markers of oxidative stress and inflammation were increased in HT+WPS group vs the controls. Furthermore, mitochondrial dysfunction in HT+WPS group was more affected than in the HT+air or HT+WPS groups. WPS inhalation in HT mice significantly increased cardiac DNA damage, cleaved caspase 3, expression of the autophagy proteins beclin 1 and microtubule-associated protein light chain 3B, and phosphorylated nuclear factor κ B, compared with the controls. Compared with HT+air mice, heart histology of WPS-exposed HT mice showed increased cardiomyocyte damage, neutrophilic and lymphocytic infiltration and focal fibrosis. We conclude that, in HT mice, WPS inhalation worsened hypertension, cardiac oxidative stress, inflammation, mitochondrial dysfunction, DNA damage, apoptosis and autophagy. The latter effects were associated with a mechanism involving NF-κB activation.

Avcs-Sonr Pilot Study: N-Terminal Pro-Brain Natriuretic Peptide Inversely Correlates with Sonr Signal in Patients with Dilated Cardiomyopathy and Reduced Left Ventricular Ejection Fraction

Background. Chronic heart failure is a very important public health problem, and brain natriuretic peptide monitoring may help in its management but faces important logistical problems. A readily available surrogate of brain natriuretic peptide would be of value in this field. We hypothesized that SonR measurements might be this brain natriuretic peptide surrogate. Methods. Patients with chronic heart failure, left ventricular ejection fraction ≤ 30% and implanted with a cardiac resynchronization therapy defibrillator able to provide SonR values underwent monthly assessment of brain natriuretic peptide levels for 1 year. The relationship between brain natriuretic peptide levels and paired SonR values was evaluated. Results. An inverse and highly significant relationship between brain natriuretic peptide levels and paired SonR values was obtained. Conclusions. We found an inverse and significant relationship between SonR values and brain natriuretic peptide levels. This finding might lead to the use of SonR values to monitor treatment and preclude hospital admissions in patients with chronic heart failure.

Incidence and prognostic significance of malignant arrhythmias during (repetitive) Holter electrocardiograms in patients with pulmonary hypertension.

In patients with pulmonary hypertension (PH), increased pulmonary vascular resistance (PVR) may lead to increased right ventricular afterload and cardiac remodelling, potentially providing the substrate for ventricular arrhythmias. Studies dealing with long term monitoring of patients with PH are rare. The present study evaluated the incidence and the types of arrhythmias retrospectively recorded by Holter ECG in patients with newly detected PH during a long-term Holter ECG follow-up. Moreover, their impact on patient survival was evaluated. Medical records were screened for demographic data, aetiology of PH, incidence of coronary heart disease, level of brain natriuretic peptide (BNP), results from Holter ECG monitoring, 6-minute walk test distance, echocardiographic data and hemodynamic data derived from right heart catheterization. Two subgroups were analyzed: 1. patients (n = 65) with PH (group 1 + 4) and derivation of at least 1 Holter ECG within 12 months from initial detection of PH and 2. patients (all PH etiologies, n = 59) with 3 follow-up Holter ECGs. The frequency and complexity of premature ventricular contractions (PVC) was classified into "lower" and "higher" (=non sustained ventricular tachycardia, nsVT) burden. Holter ECG revealed sinus rhythm (SR) in most of the patients (n = 60). Incidence of atrial fibrillation (AFib) was low (n = 4). Patients with premature atrial contractions (PAC) tend to have a shorter period of survival (p = 0.098), PVC were not correlated with significant survival differences. During follow-up PAC and PVC were common in all PH groups. Holter ECG revealed non sustained ventricular tachycardia in 19/59 patients [(32.2%); n = 6 during first Holter-ECG, n = 13 during second/third Holter-ECG]. In all patients suffering from nsVT during follow-up previous Holter ECG revealed multiform/repetitive PVC. PVC burden was not linked to differences in systolic pulmonary arterial pressure, right atrial pressure, brain natriuretic peptide and results of six-minute walk test. Patients with PAC tend to have a shortened survival. None of the evaluated parameters (BNP, TAPSE, sPAP) was correlated with the development of arrhythmias. Patients with multiform/repetitive PVC seem to be at risk for ventricular arrhythmias.

Prevalence of cirrhotic cardiomyopathy according to different diagnostic criteria: alterations in ultrasonographic parameters of both left and right ventricles before and after stress.

We estimated the frequency of cirrhotic cardiomyopathy (CCM) using all of the proposed diagnostic criteria, to describe the whole spectrum of cardiac alterations, and to investigate the role of stress in unmasking latent cases of CCM. Ninety consecutive patients were recruited. CCM was evaluated using the Montreal, the American Society of Echocardiography 2009 criteria, and the 2019 modified criteria of the CCM consortium. A dobutamine stress test was also performed. Left ventricular diastolic dysfunction (LVDD) was identified in 72 (80%), 36 (40%), and 10 (11.1%) patients based on the above criteria, respectively. None of the patients had right ventricular systolic dysfunction, either at rest or after stress. The dobutamine stress test revealed left systolic dysfunction in 4 (4.5%) patients. There was agreement among the 3 criteria that the presence of LVDD was not associated with the severity of liver disease, using Child-Pugh stage. However, patients with Child-B/C had longer QTc intervals (P=0.004), higher levels of brain natriuretic peptide (P=0.016), and greater echocardiographic E/e' ratio (P<0.001) and E/e'(s) (P=0.003), compared to Child-A patients, while a significant correlation was demonstrated between Child-Pugh score and E/e' (P<0.001), or E/e'(s) (P=0.002). The prevalence of LVDD seems to be lower than previously considered. Right ventricular function seems to remain unimpaired. A dobutamine stress uncovered only a small percentage of patients with left systolic dysfunction. Nevertheless, the aggravation of several sonographic variables during stress, particularly in Child-B/C patients, potentially indicates a higher risk for clinical heart failure during stressful invasive interventions.

Clinical value of combined plasma brain natriuretic peptide and serum cystatin C measurement on the prediction of heart failure in patients after acute myocardial infarction.

This research investigated the predictive value of combined detection of brain natriuretic peptide (BNP) and cystatin C (Cys C) in heart failure after percutaneous coronary intervention (PCI) in patients with acute myocardial infarction (AMI). Sixty-five AMI patients complicated by heart failure (HF) after PCI and 79 non-heart failure (non-HF) patients were involved in this research. The levels of Cys C and BNP were measured. Risk factors for heart failure in AMI patients after PCI were analyzed by multivariate logistic regression analysis. Efficacy of BNP and Cys C on predicting heart failure were analyzed by receiver operating characteristic (ROC) curve. Cys C and BNP levels were significantly higher in the HF group than in the non-HF group. BNP and Cys C levels were the independent influencing factors causing heart failure within one year after PCI. The area under the predicted curve (AUC) of Cys C, BNP, and combined Cys C and BNP were 0.763, 0.829, and 0.893, respectively. The combined detection of Cys C and BNP was highly valuable in predicting heart failure in AMI patients after PCI, which can be regarded as the serum markers for diagnosis and treatment of heart failure.

Age and sex variations in serum brain natriuretic peptide level following doxorubicin-induced myocardial injury in Wistar rats

Background: Brain natriuretic peptide (BNP), a cardiac hormone produced by ventricular myocytes, plays an important role in the regulation of blood pressure and fluid volume. Although serum BNP level increases with age in normals, this response and possible sex variations in the presence of drug-induced myocardial injury need to be explored further. Methods: Twenty-four Wistar rats were separated into two groups, the controls and doxorubicin-myocardial injury (DOX-MI) model group. Each group was further subdivided into aged (100–104 weeks) and young (13–14 weeks), having an equal number of males and females (n = 3). The DOX-MI Model group was given 2.5 mg/kg DOX through intra-peritoneal injection on alternate days to a cumulative dose of 12.5 mg/kg. Blood samples were then collected and centrifuged at 3000 g for 15 min and serum BNP analysis was conducted using BNP ELISA Kit (BIOTUVA LIFE SCIENCES, UK). Results: BNP was significantly lower (P = 0.003) in the aged (100–104 weeks) DOX-MI-model group compared to aged controls. Similarly, it was lower in the young (13–14 weeks) DOX-MI-Model group than the young controls, but the difference was not statistically significant (P = 0.16). The analysis between aged and young rats within each group indicated significantly higher BNP levels in the aged rats compared to the young in both groups (P = 0.01 for aged vs. young DOX-MI-Model and P = 0.02 for aged vs. young controls). Conclusion: DOX-induced-MI has caused a significant reduction in BNP production in the aged rats (100–104 weeks) compared to the young (13–14 weeks).

Carotid endarterectomy (CEA) risk stratification for adverse events at one year follow-up: the role of preoperative functional capacity scores, age, BNP and hemoglobin

The aim of the study was to evaluate combination of functional status tools (American Society of Anesthesiologists Physical Status Classification System (ASA PS)) status, Metabolic Equivalent of Task (METs), Revised Cardiac Risk Index for Pre-Operative Risk (RCRI) largely used in preoperative risk assessment with humoral variables in building powerful predictive models of Major Adverse Cardiac Cerebrovascular Events (MACCE) in a one-year follow-up after carotid endoarterectomy (CEA). All consecutive patients undergoing CEA during a 12-month period, were enrolled in this prospective observational study. Demographic data, functional capacity (FC) measured by risk stratification scores RCRI, ASA physical status, METs and preoperative levels of hemoglobin and Brain Natriuretic Peptide (Pro-BNP), coexisting comorbidities, have been collected. 201 consecutive patients undergoing CEA under local anesthesia (men 137 (68.16%), women 64 (31.84%)) with a median age of 75 years (Interquartile range (IQR) 67–80 years), Body mass index (BMI) median of 26.23 (IQR 24.4–28.89) were enrolled. Combination of all variables studied leave at a good one-year prognostic tool with AUC of 0.93 (Sensitivity (SEN) 46.6, Specificity (SPEC) 95.7). Preoperative hemoglobin correlate with Major Adverse Cardiac Cerebrovascular Events (MACCE) at 3 months (p = 0.018), while the preoperative BNP at 12 months shows correlation with adverse events (p = 0.004). Age has a significant correlation with adverse events at 12 months between demographic and anthropometric factors (p = 0.002). MACCE may adversely affect short- and long-term outcomes after CEA. Evaluation of preoperative functional capacity by RCRI, ASA physical status and METs combined with age and biomarkers such as pro-BNP and hemoglobin, may improve risk stratification in patients undergoing carotid surgery.

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.

PS-R04-2: A CASE OF SUCCESSFUL PERCUTANEOUS TRANSLUMINAL RENAL ANGIOPLASTY (PTRA) FOR RENAL ARTERY STENOSIS ASSOCIATED WITH TAKAYASU'S ARTERITIS

Introduction: In Japan, renal vascular hypertension based on renal artery stenosis (RAS) accounts for 1% of all hypertensive patients, and RAS is present in approximately 10% of autopsy cases of coronary artery disease and cerebrovascular disease. As ischemic nephropathy and complications of cardiovascular disease (CVD) due to RAS are common, early diagnosis and treatment for RAS is important. However, results of several large clinical trials have not shown the efficacy of percutaneous transluminal renal angioplasty (PTRA) for atherosclerotic RAS. Case: 51-year-old woman who diagnosed as Takayasu's arteritis (TA) 35 years ago, had been treated with 5 mg daily of prednisone. She presented with hypertension and edema in both legs a year before admission. Her examination at that time revealed increased serum creatinine from 1.0 to 1.7 mg/dL, high proteinuria (7.3 g/gCr), high renin activity (47.0 ng/mL/hr) and right RAS. Eight months before admission, she had an operation for ruptured descending aorta. She had recurrent episodes of dyspnea on exertion, worsening leg edema and severe hypertension and was admitted to the hospital for the treatment. Clinical course: In addition to severe hypertension (190/80 mmHg) and progression of RAS, she had pulmonary congestion, high brain natriuretic peptide (BNP) level (1149.5 pg/mL), increasing creatinine levels (Cr 3.1 mg/dL), and left non-functioning kidney on admission. Despite taking 8 types of antihypertensive drugs and diuretics without renin-angiotensin system inhibitors, blood pressure and fluid retention were poorly controlled, and thus we decided to perform PTRA for the right RAS. After the PTRA, edema, hypertension and pleural effusion had been dramatically improved. In addition, we could observe decrease of serum creatinine (Cr 1.6 mg/dL), proteinuria (0.5 g/gCr) and plasma renin activity (1.9 ng/mL/hr). Therefore, we reduced the antihypertensive drugs from 8 to 2. Discussions: Although the benefit of PTRA for RAS associated with TA remains unclear, the clinical course suggests that the success of PTRA in this case may be related to the fact that the RAS was complicated by TA. It also suggests that we should consider PTRA in cases of hypertension and pulmonary congestion associated with RAS which are difficult to control like this case. Conclusion: We have experienced a case of RAS associated with TA that was successfully treated with PTRA.

Exosomes secreted from bone marrow mesenchymal stem cells suppress cardiomyocyte hypertrophy through Hippo-YAP pathway in heart failure.

Mesenchymal stem cells-derived exosomes (MSCs-exosomes) reportedly possess cardioprotective effects. This study investigated the therapeutic potential and mechanisms of MSCs-exosomes on heart failure (HF). H9c2 cells were used to establish a cardiomyocyte hypertrophy model by angiotensin II (Ang II) treatment. Isolated MSCs-exosomes were identified by transmission electron microscope and CD63 detection. Apoptosis rate was measured by terminal deoxynucleotidyl transferase (TdT) dUTP Nick-End Labeling (TUNEL) assay. Levels of inflammatory factors [interleukin (IL)-1β, IL-4, IL-6, and tumor necrosis factor (TNF)-α] and brain natriuretic peptide (BNP) were determined by ELISA. Expression of apoptosis-related proteins [Bax, B-cell lymphoma-2 (Bcl-2), and caspase 3] and Hippo-Yes-associated protein (YAP) pathway-related proteins [YAP, phosphor (p)-YAP, and tafazzin (TAZ)] was detected by western blotting. Cardiomyocyte hypertrophy of H9c2 cells induced by Ang II was ameliorated by MSCs-exosomes treatment. MSCs-exosomes downregulated Bax and caspase 3 levels and upregulated Bcl-2 level in Ang II-induced H9c2 cells. MSCs-exosomes also reduced the levels of BNP, IL-1β, IL-4, IL-6, and TNF-α in Ang II-induced H9c2 cells. Meanwhile, p-YAP was downregulated and TAZ was upregulated after MSCs-exosomes administration. In conclusion, MSCs-exosomes alleviate the apoptosis and inflammatory response of cardiomyocyte via deactivating Hippo-YAP pathway in HF.

Association of Brain Natriuretic Peptide Levels at Time of Injury with Morbidity and Mortality in Patients with Surgically Treated Hip Fractures.

A retrospective chart review of 455 hip fractures in patients ≥60 years old that were operatively treated between February 2014 and July 2018 was performed. Patients were included if they had a BNP level within 48 hours after injury (BNPi). Specific perioperative (≤7 days), 30-day, 1-year, and 2-year postoperative complications were recorded. Wilcoxon rank-sum tests were used to determine if higher BNPi values were associated with greater morbidity. The complications associated with higher BNPi values were further analyzed to assess if they were predictive of mortality, using univariate and multivariable analyses. Higher BNPi was significantly associated with greater morbidity at all postoperative time points and with higher mortality at 1 and 2 years postoperatively. Furthermore, several complications including cardiac failure or exacerbation and altered mental status were associated with mortality at all time points in univariate analysis and at many time points in multivariable analysis. Patients with higher BNPi levels were more likely to develop complications up to 1 year postoperatively, and several of these complications were associated with increased mortality. Future studies to determine if delaying surgery until BNP levels are normalized or lowered may help guide management, and may be useful in determining the need for further medical optimization. Future studies aimed at defining a threshold BNP value at the time of injury may also help in better managing patients preoperatively. Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.

Massive Left Ventricular Thrombus in the Setting of COVID-19–Induced Systemic Thrombi

A 58-year-old White man with no known medical history initially presented to the emergency department for fatigue and was ultimately diagnosed with COVID-19. He was in stable condition and discharged to quarantine at home. He returned to the emergency department 2 weeks later with a chief report of progressive pain and swelling of his legs. Initial vitals were remarkable for a heart rate of 115/minute. Physical examination revealed edematous and erythematous lower extremities with weeping wounds. Laboratory workup was remarkable for a white blood cell count of 12.7 × 1,000/μL, platelet count of 81 × 1,000/μL, troponin I level of 0.678 ng/mL, brain natriuretic peptide level of 4,000 pg/mL, C-reactive protein level of 121 mg/L, lactate level of 3.7 mmol/L, and international normalized ratio of 1.5.Chest computed tomographic angiography revealed acute emboli of subsegmental pulmonary arteries of the left upper, middle, and lower lobes (Fig. 1). Echocardiogram revealed a severely dilated left ventricle with apical akinesis and an ejection fraction of 10% to 15%. Large, layered thrombi were seen in the apex of the left and right ventricles (Fig. 2). Duplexes of the lower extremities showed acute occlusive calf vein thrombi in the right posterior tibial and bilateral peroneal veins. Arteries were patent in both lower extremities. Venous duplex of the right upper extremity revealed acute superficial venous thrombi in the right basilic and cephalic veins. Cardiac magnetic resonance imaging was performed to assess viability, which revealed significant transmural scarring and a large thrombus (8 × 6 × 5 cm) occupying the mid- and complete apical left ventricle cavity (Fig. 3). Multiple small thrombi in the right ventricle apex were seen.Given the thrombocytopenia on presentation, there was concern for disseminated intravascular coagulation; however, with such extensive clot burden, the patient was started on a heparin drip. Four days later, he sustained a cardiac arrest secondary to venous thromboembolism. Upon achieving return of spontaneous circulation, he was taken for left heart catheterization, which revealed severe triple-vessel disease. Cardiothoracic surgery was consulted, but it was determined that the patient to be too high risk to undergo coronary artery bypass graft or operative thrombectomy. Ultimately, his clinical status deteriorated, and the patient along with family proceeded with comfort measures.SARS-CoV-2 infection primarily affects the lower respiratory tract, but there are reports of COVID-19–induced cardiac complications, including acute coronary syndromes, arrythmias, myocarditis, and thrombosis.1 Venous thromboembolism is reported to occur in approximately 30% of patients with COVID-19, but intracardiac thrombus in very rare.2 Cardiac thrombus should be considered in the diagnosis of COVID-19 in patients presenting with chest pain and leg swelling.

S-46-4: NONDIPPER PULSE RATE PATTERN WAS ASSOCIATED WITH BLOOD PRESSURE VARIABILITY AND INCREASE OF BNP: J-HOP STUDY

Background: The association between nondipper pulse rate (PR) pattern was reported. However, the association between nondipper PR pattern, blood pressure variability and hypertensive target organ damage remains unclear. Methods: Ambulatory BP monitoring (ABPM) was conducted in 1,003 hypertensive patients enrolled in the Japan Morning Surge Home Blood Pressure (J HOP) Study. Ambulatory BP monitoring was performed on a weekday with an automatic system that recorded the wearers BP and PR every 30 minutes for 24 hours. Nondipper PR status was defined as (awake PR minus sleep PR)/awake PR &lt; 0.1, and we evaluated standard deviation (SD) of systolic BP in daytime and nighttime as BP variability. We also measured the brain natriuretic peptide level (BNP), and conducted echocardiography to estimate the left ventricular mass index (LVMI). Results: The SD of systolic BP in nighttime, BNP and LVMI in patients with nondipper PR (N = 247) were higher than that in patients with dipper PR (N = 756, SD of systolic BP: 13.3 ± 4.6 vs. 12.7 ± 4.1 mmHg, p = 0.041; median BNP: 25.2 vs. 17.6 pg/dL, p &lt; 0.001, LVMI: 101.4 ± 29.1 vs. 97.3 ± 42.2 g/m2, p = 0.021). Systolic BP in nighttime in patient with nondipper PR was similar to that in patient with dipper PR (119.5 ± 15.2 vs. 119.9 ± 15.1 mmHg, p = 0.63). The SD of systolic BP in nighttime was associated with BNP and LVMI (BNP: r = 0.08, p = 0.006; LVMI r = 0.10, p = 0.001). Nondipper PR was independently associated with BNP (β = 0.10, p &lt; 0.001), but not with LVMI (β = 0.03, p = 0.37) after adjustment for systolic BP and SD of systolic BP in nighttime. Conclusions: Nondipper PR pattern was associated with blood pressure variability and hypertensive target organ damage in patients with cardiovascular risk factor.