Plasma NT-proBNP Research Articles

Cardioprotection of Repeated Remote Ischemic Conditioning in Patients With ST-Segment Elevation Myocardial Infarction.

BackgroundRepeated remote ischemic conditioning (RIC) after myocardial infarction (MI) has been shown to improve left ventricular (LV) remodeling in the experimental studies, but its cardioprotective effect in patients with ST-segment elevation myocardial infarction (STEMI) is still unknown.ObjectiveTo investigate whether repeated RIC started early after primary percutaneous coronary intervention (PCI) can improve LV function in patients with STEMI.MethodsPatients with STEMI treated by primary PCI were included and randomized to the repeated RIC group (n = 30) or the control group (n = 30). RIC was started within 24 h after PCI and repeated daily for 1 week, using an Auto RIC device. 3D speckle-tracking echocardiography (STE) was used to assessed LV function. The primary study endpoint was the change in LV global longitudinal strain (GLS) from baseline to 1 month after PCI.ResultsThe repeated RIC group and the control group were well-matched at baseline including mean GLS (−9.8 ± 2.6% vs. −10.1 ± 2.5%, P = 0.62). Despite there was no significant difference in mean GLS at 1 month between the two groups (−11.9 ± 2.1% vs. −10.9 ± 2.7%, P = 0.13), the mean change in GLS from baseline to 1 month was significantly higher in the treatment group than in the control group (−2.1 ± 2.5% vs. −0.8 ± 2.3%, P = 0.04). There were no significant differences in the changes in global circumferential strain (GCS), global area strain (GAS), global radial strain (GRS), LV ejection fraction (LVEF), LV end-diastolic volume (LVEDV), and LV end-systolic volume (LVESV) between the two groups. Peak creatine kinase isoenzyme-MB, peak high-sensitivity troponin T, and plasma N-terminal pro-brain natriuretic peptide (NT-proBNP) levels at 24 h after PCI did not differ significantly between the two groups, but NT-proBNP levels at 1 week were significantly lower in the treatment group than in the control group [357.5 (184.8–762.8) vs. 465.0 (305.8–1525.8) pg/ml, P = 0.04].ConclusionDaily repeated RIC started within 24 h after PCI can improve GLS and reduce plasma NT proBNP levels in patients with STEMI.

Dapagliflozin Attenuates Myocardial Fibrosis by Inhibiting the TGF-β1/Smad Signaling Pathway in a Normoglycemic Rabbit Model of Chronic Heart Failure.

Recent studies have shown that sodium-glucose cotransporter-2 (SGLT2) inhibitors play a beneficial role for normoglycemic patients with heart failure (HF). However, the underlying mechanism remains largely unexplored. In the present study, we aimed to investigate the cardioprotective effect of SGLT2 inhibitors in a normoglycemic rabbit model of chronic heart failure (CHF) and its potential mechanism was also explored. A total of 24 male New Zealand white rabbits were randomly divided into the sham group, HF group, perindopril group, and dapagliflozin (DAPA) group. The normoglycemic CHF model was established by aortic constriction for 12 weeks. In the 13th week, DAPA (1 mg/kg/day) or perindopril (0.5 mg/kg/day) was administered by oral gavage daily for 10 weeks. Both the sham group and HF group were given normal saline via gavage. After 10 weeks, the heart structure and function were evaluated by echocardiography and plasma NT-proBNP. Moreover, cardiac fibrosis was analyzed using immunohistochemistry, Masson’s trichrome staining, and Western blotting analysis. The results showed that DAPA improved the myocardial structure and function of normoglycemic CHF rabbits and ameliorated myocardial fibrosis. Further study indicated that DAPA suppressed cardiac fibrosis by inhibiting the transforming growth factor β1 (TGF-β1)/Smad signaling pathway. Collectively, our findings showed that DAPA could ameliorate cardiac fibrosis in normoglycemic CHF rabbits by inhibiting the TGF-β1/Smad signaling pathway.

Impact of a home-based cardiac rehabilitation program in heart failure during the COVID-19 pandemic

Funding AcknowledgementsType of funding sources: Other. Main funding source(s): This work was financially supported by the project POCI-01-0145-FEDER-030011, funded by FEDER, through COMPETE2020-POCI, and by national funds, through FCT/MCTES (PTDC/MEC-CAR/30011/2017). CIAFEL, UnIC and UMIB are supported by national funds through Fundação para a Ciência e Tecnologia, I.P. [(UIDB/00617/2020), (UIDB/00051/2020 and UIDP/00051/2020), and (UIDB/00215/2020 and UIDP/00215/2020), respectively]. CS received an individual grant from CAPES [BEX 0554/14-6].IntroductionCardiac rehabilitation (CR) is an evidence-based recommended treatment of heart failure (HF) patients. During the COVID-19 pandemic, the shutdown of CR centers was necessary to limit the infection risk among high-risk patients. The integration of a home-based CR (HBCR) program in CR units can help to improve the delivery of care and improve cardiovascular outcomes of HF patients.PurposeTo assess the effectiveness of an HBCR program in HF patients.MethodsThis is a sub­study of the EXercise InTervention in Heart Failure trial (EXIT-HF), which include forty-nine HF patients (preserved and reduced ejection fraction). The HBCR program consisted in 12-week combined exercise program (60%-80% of peak oxygen consumption (VO2 peak)), 2 training sessions per week, for a total of 24 sessions. Patients performed 4 supervised training sessions and the remaining sessions at home. All patients performed a cardiopulmonary exercise test (VO2 peak), the 6-minute-walking test (6MWT), collected blood analysis (plasma NT-proBNP), and answered the Minnesota Living with Heart Failure Questionnaire.ResultsForty-two patients (86%) complete at least 80% of prescribed training sessions (age: 61.1±12; FEVE: 37.1±10.8). The HBCR program improve VO2 peak from 18.3 to 20.1ml/kg/min (+1.8 ml/kg/min; 95%IC:1.4 to 2.4; p<0.001) and the walked distance at the 6MWT from 462 to 512 meters (+49 meters; 95%IC: 38 to 60; p<0.001). In addition, overall quality of life was improved (-13 points; 95%IC:-7.8 to -18.5; p<0.001), as well physical (-6.3 points; 95%IC:-3.5 to -9; p<0.001) and emotional dimension of quality of life (-2.8points ; 95%IC: -0.9 to -4.7; p=0.06). No significant change was found in NT-proBNP levels (820±1220 vs 674±903; p=0.285).ConclusionsOur results showed that HBCR is feasible and can improve functional capacity and quality of life in HF patients.

Mechanisms in Chronic Kidney Disease and Associated Cardiovascular Remodeling Contributes to the Progression of Cognitive Impairment in Women

IntroductionIn end‐stage chronic kidney disease (CKD) (stages 4‐5) the prevalence of cognitive impairment (CI) has been estimated at 30‐60%, twice the values observed in age‐ and sex‐matched controls. CKD is greater in females vs. males due to a higher risk of renal infections, especially during the pregnancy, which may result in the renal complications later in life, when the level of protective estrogen declines. Cardiovascular diseases (CVD) including hypertension and increased central arterial stiffness (CAS) accompany CKD development across all stages of this disease. 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. Moreover, PP is a cardiovascular risk factor independent on PCI in women &gt;55 years.HypothesisThe aim of the study was to determine whether CKD potentiates development of CI due to cardiovascular remodeling and whether CI in CKD is more pronounced in women. Furthermore, this study also aimed to determine whether reduced estrogen levels in older women with CKD contribute to the progression of CI.MethodsAll research was performed in accordance with the guidelines and regulations set forth by the Declaration of Helsinki regarding the use and enrollment of human subjects in research. A total of 26 female CKD patients (age 45‐50 years and older, CKD stage 4, GFR 15‐29, and Creatinine &gt; 1mg/dL) and 30 age and sex‐ matched healthy control patients were enrolled with exclusion criteria (history of HIV, hepatitis, malignancies, admission and/or surgery for trauma, head injury and pregnancy at time of enrollment). Blood pressure (systolic and diastolic blood pressure (SBP, DBP) was measured, clinical blood work, echocardiography (ECHO) and mini‐mental state examination (MMSE) was performed as well as levels of amyloid beta‐40 (Aβ‐40) measured. PCI was calculated as difference between peak systolic and end diastolic flow velocity, divided by the flow velocity. Estrogen levels were measured in the plasma samples. The data were analyzed by unpaired two‐tailed t‐test and Pearson correlation with P values adjusted for false discovery rate.ResultsCKD patients had higher SBP, PP, PCI, LV systolic and diastolic volume (estimated by ECHO), lower LV ejection fraction, higher plasma NT‐proBNP and AST (CVD markers), glucose, triglycerides, plasma Aβ‐40 (Alzheimer’s disease marker), BUN and creatinine (CKD markers) and lower score in MMSE vs. healthy control (p&lt;0.05). Plasma estrogen levels were significantly lower in CKD patients which correlated with the cognitive test scores and the renal function. Cognitive test results positively correlated with LV stroke volume, negatively correlated with PCI, a measurement of pulsatility of blood pressure, and negatively correlated with plasma ASP, a marker of CVD.ConclusionHigher PP, PCI, plasma Aβ‐40 and lower levels of estrogen and lower score in MMSE in female CKD patients supports our hypothesis that cardiovascular remodeling in women with CKD contributes to the development and progression of CI.

Serum Levels of NT-Pro BNP in Patients with Preeclampsia.

ObjectiveThis study aims to determine the serum levels of NT-proBNP in women with preeclampsia with and without severe signs and to evaluate the cardiovascular risks in these two groups of participants.MethodsA descriptive cross-sectional study was conducted on 52 women with preeclampsia in the Department of Gynecology and Obstetrics – Hue Central Hospital, from August 2019 to September 2020.ResultsIn preeclampsia women, the rate of hypertension in stage 3, stage 2, and stage 1 were 46.1%, 32.7%, and 21.2%, respectively. The average Sokolow-Lyon index in the preeclampsia group with and without severe signs was 22.25 ± 7.38mm, 20.16 ± 5.54mm, respectively. The average left ventricular mass index in the group of preeclampsia patients without and with severe signs was 92.27 ± 14.56g/m2 and 120.68 ± 16.47g/m2, respectively. The average ejection fraction in the group of preeclampsia patients without severe signs and with severe signs was 65.11 ± 3.45%, 56.21 ± 7.12%, correspondingly. In contrast, the difference between the two groups was statistically significant with p < 0.05. The plasma NT-proBNP level in the preeclampsia group without severe signs was 349.12 ± 93.51pg/mL, whereas the concentration in the preeclampsia group with severe signs was 725.32 ± 290.46pg/mL (p < 0.05).ConclusionThe NT-proBNP level was statistically significantly increased in the patients with preeclampsia. Analyzing and comparing the figures and changes found in two groups of PE patients, with and without severe signs, we suggest that women diagnosed with PE with severe signs have a higher risk of developing cardiovascular problems forthwith and henceforth.

IDF21-0263 The association of plasma NT-proBNP level and progression of diabetic nephropathy

Background: Diabetic nephropathy (DN) is one of the most serious microvascular complications in patients with diabetes. Natriuretic peptides are synthesized and released from the atrial and ventricular myocardium. In response to cardiomyocyte stimulation, such as, ischemic injury, pressure overload, and volume overload, the precursor pro-brain natriuretic peptide (BNP) is divided into the hormonally active BNP and inactive N-terminal (NT)-proBNP. NT-proBNP has already been proved to be a marker for cardiovascular events and/or mortality in patients with diabetes, and patients undergoing peritoneal dialysis/hemodialysis.

Relationship of NT-proBNP to All-Cause Death and Heart Transplant in Children with Ventricular Dysfunction and Compared to Adults with Heart Failure

<h3>Purpose</h3> Plasma NT-proBNP concentration is a widely used diagnostic biomarker for heart failure (HF) in adults and children. We sought to determine whether NT-proBNP concentrations predicted the risk of heart transplantation or death in pediatric HF patients. <h3>Methods</h3> We studied medical records from 109 children with HF in the IBM Watson Explorys database and from 150 children in the Cardiac Biomarkers in Pediatric Cardiomyopathy (PCMR) study. Nonlinear regression with an Emax function was used to model the relationship between NT-proBNP concentrations and the number of events in the two cohorts and with adult patients from Explorys. <h3>Results</h3> All children in the PCMR cohort had dilated cardiomyopathy, whereas the Explorys cohort also included children with congenital heart diseases (Table). Mean age at diagnosis was 3 years in the Explorys cohort and 1.4 years in the PCMR cohort; median NT-proBNP concentrations were 1250 pg/mL and 183.5 pg/mL, respectively. The percentage of deaths and transplantations was higher in the Explorys cohort (7% and 22%, respectively, over 2 years) than in the PCMR cohort (3% and 16%, respectively, over 5 years). Mean estimates of NT-proBNP concentration indicative of half-maximum risk for events (EC50 values) at 2 and 5 years were 3730 pg/mL and 4199 pg/mL, values both close to the mean of 3880 pg/mL established for adults with HF (Figure). <h3>Conclusion</h3> NT-proBNP concentration is suitable for estimating the risk of mortality and morbidity in children with HF, independent of age, and is a candidate surrogate marker for clinical outcome both in adults and children with HF.

PACAP-38 and PAC1 Receptor Alterations in Plasma and Cardiac Tissue Samples of Heart Failure Patients.

Pituitary adenylate cyclase activating polypeptide-38 (PACAP-38) is a multifunctional neuropeptide, which may play a role in cardioprotection. However, little is known about the presence of PACAP-38 in heart failure (HF) patients. The aim of our study was to measure the alterations of PACAP-38 like immunoreactivity (LI) in acute (n = 13) and chronic HF (n = 33) and to examine potential correlations between PACAP-38 and HF predictors (cytokines, NT-proBNP). Tissue PACAP-38 LI and PAC1 receptor levels were also investigated in heart tissue samples of patients with HF. Significantly higher plasma PACAP-38 LI was detected in patients with acute HF, while in chronic HF patients, a lower level of immunoreactivity was observed compared to healthy controls (n = 13). Strong negative correlation was identified between plasma PACAP-38 and NT-proBNP levels in chronic HF, as opposed to the positive connection seen in the acute HF group. Plasma IL-1 β, IL-2 and IL-4 levels were significantly lower in chronic HF, and IL-10 was significantly higher in patients with acute HF. PACAP-38 levels of myocardial tissues were lower in all end-stage HF patients and lower PAC1 receptor levels were detected in the primary dilated cardiomyopathy group compared to the controls. We conclude that PACAP-38 and PAC1 expression correlates with some biomarkers of acute and chronic HF; therefore, further studies are necessary to explore whether PACAP could be a suitable prognostic biomarker in HF patients.

Risk factors and diagnostic value of urinary N-terminal pro-brain natriuretic peptide for verification of heart failure in human immunodeficiency virus-infected patients

Aim. To determine the risk factors and diagnostic value of urinary N-terminal probrain natriuretic peptide (NT-proBNP) for verification of heart failure in human immunodeficiency virus (HIV)-infected patientsMaterial and methods. This cross-sectional screening clinical trial included 115 HIV-infected patients who were hospitalized during 24 months. The patients were divided into 2 groups, depending on the data suggestive of HF and the blood and urinary NT-proBNP concentration. So, group 1 included 69 HIV-infected patients with HF symptoms and increased blood and urinary NTproBNP, while group 2 — 46 HIV-infected patients not meeting HF criteria. NTproBNP concentration was determined on Immulite 1000 Immunoassay System (DPC, USA) in blood plasma and frozen urine using Vector Best reagents (Russia).Results. Correlation analysis revealed a significant direct moderate correlation between blood and urinary NT-proBNP in the entire cohort of studied patients (r=0,367; p&lt;0,05). Urinary NT-proBNP ≥8,6 pg/ml ml is diagnostic for HF verification in HIV-infected patients. Significant differences between the groups were obtained in the incidence of ventricular arrhythmias, viral hepatitis B and C, liver cirrhosis, infective endocarditis, other inflammatory diseases, thrombocytopenia, left ventricular (LV) diastolic dysfunction and its severity. In addition, there were differences in LV mass index, left atrial volume index, incidence of LV hypertrophy and left atrial enlargement, concentration of hemoglobin and CD4 cells &lt;200 in 1 µl. The preserved LV ejection fraction was detected significantly more often (p&lt;0,001). Conclusion. In HIV-infected patients, blood plasma and urinary NT-proBNP concentration correlates with each other. Urinary NT-proBNP ≥8,6 pg/ml is diagnostic for HF verification in HIV-infected patients. Risk factors and features of developing HF, estimated by NT-proBNP concentration in frozen urine in HIV-infected patients, are comparable to data obtained from blood plasma NTproBNP.

N-TERMINAL PROHORMONE OF BRAIN NATRIURETIC PEPTIDE IN THE DIAGNOSIS AND MANAGEMENT OF PERSISTENT PULMONARY HYPERTENSION IN NEWBORNS

Objective: This study aimed to investigate the levels and utility of amino/N-terminal prohormone of brain natriuretic peptide (NT-proBNP) in the diagnosis of neonatal persistent pulmonary hypertension (PPHT). Materials and Methods: Infants born at ≥34 weeks of gestation were included in this retrospective cross-sectional study. In total, 33 newborns diagnosed with PPHT were included in the patient group and 50 healthy newborns were included in the control group. Patient and control groups were compared in terms of plasma NT-proBNP levels measured in the umbilical cord (UC) and at 72 hours of life. Results: The NT-proBNP levels in UC and at 72 hours were significantly higher in neonates with PPHT compared to controls (p&lt;0.01). For the diagnosis of PPHT, UC NT-proBNP cut-off value was &gt;2760.5 pg/ml, sensitivity was 90.7%, and specificity was 96.6% (p&lt;0.01). For NT-proBNP at 72 hours, the cut-off value was &gt;1414 pg/ml, sensitivity was 95.9%, and specificity was 91.2% (p&lt;0.01). The mean UC NT-proBNP levels were 1094.7±603 pg/ml and mean NT-proBNP levels at 72 hours were 875.7±423 pg/ml in the control group. Conclusion: NT-proBNP levels are high during the initial days of life. They are useful in the diagnosis and follow-up of PPHT in newborns with hypoxemic respiratory failure and high fraction of inspired oxygen (FiO2) requirement, especially in cases where transthoracic echocardiography (TTE) cannot be performed.&nbsp;

The Association between NTproBNP Biomarker Levels and Clinical Symptoms of Cardiac Septal Defects in Children

BACKGROUND: In a cardiac septal defect, there is left-to-right shunt at the atrial, ventricle level, or both. This causes clinical symptoms of heart failure, pulmonary hypertension, or malnutrition. NTproBNP is synthesized and released into the circulation by the ventricular myocytes in response to pressure, volume overload, and increase in myocardial wall stress. AIM: This study aims to evaluate relationship between NTproBNP levels and clinical symptoms of cardiac septal defect. PATIENTS AND METHODS: This cross-sectional study was conducted from April to August 2021 at Moh Husin Hospital, Palembang, Indonesia. The presence of heart failure was determined using the modified Ross score. Nutritional status was defined on anthropometric measurement, and data were plot to weight to height Z-score chart. The presence of pulmonary hypertension was measured by Doppler echocardiography. RESULTS: A total of 75 cardiac septal defect patients were included in this study. A similar plasma NTproBNP of 554 pg/ml was determined as the cut-off point for predicting heart failure and pulmonary hypertension, with a sensitivity of 57.1% and 54.5%, specificity of 85% and 80.9%, with area under receiver operating characteristic (ROC) of 0.706 and 0.716 respectively. For malnutrition, plasma NTproBNP of 429 pg/ml was found to have sensitivity, specificity, and area under ROC of 54.3%, 77.5%, and 0.640, respectively. The multivariate logistic regression showed that NTproBNP &gt;554 pg/ml and &gt;429 pg/ml had a 6-fold higher odds of having heart failure, an 8-fold higher odds of having pulmonary hypertension, and a 4-fold odds of having malnutrition. CONCLUSION: NTproBNP is a biomarker that is strong enough to predict clinical symptoms of heart failure, pulmonary hypertension, and malnutrition in children with cardiac septal defect.

Efficacy of intermittent inhaled iloprost in inoperable chronic thromboembolic pulmonary hypertension

PH (pulmonary hypertension) targeted therapy may play an essential role in chronic thromboembolic pulmonary hypertension (CTEPH) patients considered inoperable. Given the limited number of PH-targeted drugs approved for CTEPH, reliable long-term data are necessary on the effects of PH-targeted drugs in patients with inoperable CTEPH. We aimed to evaluate the efficacy and safety of intermittent inhaled iloprost in inoperable CTEPH. Methods. The open randomized controlled trial included 22 inoperable CTEPH patients (aged (Me (25%; 75%)) 48,3 (38,4; 59,5) years; 63.6% females; 9.1% with WHO functional class (FC) IV, 72.7% with WHO-FC III, 18.2% with WHO-FC II; 6-minute walking test (6-MWT) distance of 348 (145; 443) m; mean pulmonary artery pressure (mPAP) of 41.8 (29.3; 52.8) mmHg; tricuspid annular plane systolic excursion (TAPSE) of 16.3 (14.5; 18.2) mm; plasma NT-proBNP of 853.8 (562.2; 1124.2) pg/mL). The patients were enrolled 3 – 6 months after acute pulmonary embolism and were randomized 1:1 to receive either standard therapy with vitamin K antagonists and, if indicated, oxygen and diuretics or inhaled iloprost 5.0 µg / inhalation 4 times a day for 2 weeks every 3 months for 2 years in addition to the standard of care. Efficacy endpoints included changes from baseline in 6-MWT, WHO-FC, echo-parameters, inflammatory markers, time to clinical worsening, and all-cause mortality. Results. At baseline (prior to therapy), there were no significant differences between iloprost and control groups. Levels of C-reactive protein and the interleukin (IL)-1b, IL-6, IL-8, γ-IF, and TNF-α cytokines were increased. At month 24, a mean 6-MWT distance increased by 215 m (p &lt; 0.001) in the patients receiving inhaled iloprost and by 137 m in the control patients (p &lt; 0.01). The control-adjusted difference was +78 m (p = 0.03). WHO-FC improved by two classes in 63.6% in iloprost group vs 0% in the control group (p = 0.028), by one class in 36.4% vs 30% (p = 0.091), and remained the same in 0% vs 70 % (p = 0.018), respectively. Inhaled iloprost delayed the time to clinical worsening (p = 0.0064). Improvements were noted in control-adjusted changes in ePASP (–18.6 mmHg; p = 0.0065), TAPSE (+2.4 mm; p = 0.028), and plasma NT-proBNP (–256.9 pg/mL; p &lt; 0.01). The levels of inflammation decreased significantly in the iloprost group, while remained unchanged in the control group. Combination therapy with inhaled iloprost was tolerated well. One patient died in the control group (p = 0.093). Conclusion. Long-term intermittent inhaled iloprost for patients with inoperable CTEPH may improve their clinical status, hemodynamics, and anti-inflammatory status.

Effects of dexmedetomidine and its reversal with atipamezole on echocardiographic measurements and circulating cardiac biomarker concentrations in normal cats.

To investigate the effects of dexmedetomidine (DXM) and its subsequent reversal with atipamezole (APM) on the echocardiogram and circulating concentrations of cardiac biomarkers in cats. 14 healthy cats. Cats underwent echocardiography and measurements of circulating cTn-I and NT-proBNP concentrations before (PRE) and during (INTRA) DXM sedation (40 µg/kg IM) and 2 to 4 (2H POST) and 24 (24H POST) hours after reversal with APM. Administering DXM significantly decreased heart rate, right ventricular and left ventricular (LV) outflow tract velocities, and M-mode-derived LV free-wall thickness; increased LV end systolic diameter and volume; and caused valvar regurgitation. While sedative effects resolved within 25 minutes of APM reversal, the evolution of echocardiographic changes was mixed: LV ejection fraction and mitral valvar regurgitation score were different at 2H POST than at both INTRA and PRE (partial return toward baseline), LV end-diastolic volume was different PRE to INTRA and INTRA to 2H POST but not different PRE to 2H POST (full return toward baseline), and M-mode-derived LV free-wall thickness was significantly different from PRE to INTRA and PRE to 2H POST (no return toward baseline). Serum cTn-I and plasma NT-proBNP concentrations increased significantly with DXM, which remained significant 2H POST. Administration of DXM and APM reversal produced changes in echocardiographic results and in circulating cTn-I and NT-proBNP concentrations. Understanding these changes could help veterinarians differentiate drug effects from cardiac disease.

A Preclinical Rat Model of Heart Failure With Preserved Ejection Fraction With Multiple Comorbidities.

Heart failure with preserved ejection fraction (HFpEF) is a common complex clinical syndrome for which there are currently few evidence-based therapies. As patients with HFpEF very often present with comorbidities comprising the metabolic syndrome, we hypothesized, that metabolic syndrome could lead over time to the development of diastolic dysfunction and HFpEF. Obesity-prone rats were exposed to high-fat diet and compared to obesity-resistant rats fed with standard chow. Phenotyping of metabolic syndrome, associated with echocardiographic and cardiac hemodynamic measurements, was performed after 4 and 12 months. Blood and myocardial tissue sampling were performed for pathobiological evaluation. High-fat diet in obesity-prone rats elicited metabolic syndrome, characterized by increased body and abdominal fat weights, glucose intolerance and hyperlipidemia, as well as increased left ventricular (LV) systolic pressure (after 12 months). This was associated with LV diastolic dysfunction (assessed by increased LV end-diastolic pressure) and pulmonary hypertension (assessed by increased right ventricular systolic pressure). Echocardiography revealed significant concentric LV hypertrophy, while LV ejection fraction was preserved. LV remodeling was associated with cardiomyocyte hypertrophy, as well as myocardial and perivascular fibrosis. Circulating levels of soluble ST2 (the interleukin-1 receptor-like) markedly increased in rats with HFpEF, while plasma NT-proBNP levels decreased. RNA-sequencing analysis identified clusters of genes implicated in fatty acid metabolism and calcium-dependent contraction as upregulated pathways in the myocardium of rats with HFpEF. High-fat diet during 12 months in obesity-prone rats led to the development of a relevant preclinical model of HFpEF with multiple comorbidities, suitable for investigating novel therapeutic interventions.

The Utility of Plasma N- Terminal Brain Natriuretic peptide (NT- Pro BNP) as a Biomarker to Differentiate Cardio embolic Stroke from Non-Cardio embolic Stroke.

TITLE: The Utility of Plasma N- Terminal Brain Natriuretic Peptide (NT- Pro BNP) as a Biomarker to Differentiate Cardio embolic Stroke from Non-Cardio embolic Stroke. PURPOSE: To measure plasma NT-Pro BNP in patients with acute ischemic stroke and investigate whether the plasma NT- pro BNP level can be a useful bio marker to differentiate cardio embolic (CE) stroke from non-cardio embolic (NCE) stroke or not. STUDY DESIGN: In our analytic observational prospective study, 66 patients were enrolled within 24 hours of the onset of acute ischemic stroke and met inclusion and exclusion criteria. METHODOLOGY: Plasma NT-pro BNP level was performed in each patient. Clinical observations were recorded on special performa designed for the study. They were classified in to four groups: Cardioembolic (CE), Large artery atherosclerosis (LAA), Small-vessel disease (SVD) and other subtypes according to TOAST classification. Study outcome was measured by applying appropriate statistical tests at the end of all patient enrolments. RESULTS: Out of 66 patients, 21(31.81 %) were cardioembolic whereas 45 (68.18%) patients were in non-cardioembolic (NCE) group. The result showed that plasma NT pro BNP levels were significantly higher in CE group than NCE group (p value&lt;0.001). The optimal cut off point for NT pro BNP levels to differentiate CE stroke from NCE stroke was &gt; 594 pg./ml with 93.33% Specificity and 66.67% Sensitivity. CONCLUSION: As plasma biomarker NT-pro BNP has a good sensitivity, specificity and accuracy for early identification of cardio embolic stroke.

Value of Combined Plasma NGAL, Cystatin C and NT-proBNP in the Diagnosis of Cardiorenal Syndrome Type 1

Background: The presence of acute kidney injury in the setting of acute heart failure (AHF) or acute decompensated heart failure (ADHF) is very common occurrence and was termed cardiorenal syndrome 1 (CRS1). Neutrophil gelatinase-associated lipocalin (NGAL) in the blood and urine is one of the earliest biomarkers of acute kidney injury due to ischemia or renal toxicity. Cystatin C is early marker of renal dysfunction. NT-pro BNP is valuable in the diagnosis, prognosis and treatment of acute and chronic heart failure. This study was aimed to evaluate the diagnostic efficacy of the combination of plasma NGAL, Cystatin C and NTproBNP in diagnosis of CRS1. Methods: there were 139 patients with AHF or ADHF in the department of Cardiovascular resuscitation and Interventional cardiology at Ho Chi Minh City 115People Hospital from November 2018 to May 2019. This was a prospective cohort study. Results: there were 48 cases (rate 34.5%) with CRS1, mean age 66.12 ± 15.77, men accounted for 50.4%. There were no significant differences of vital signs on admission, diagnosis, type of heart failure between CRS1 and Non-CRS1 groups. The urea, creatinin on first day (creatininD1) and third day (creatininD3), NT-pro BNP, Cystatin C, NGAL levels were higher in the group with CRS1 than Non-CRS1, the difference was statistically significant p 353.23 ng/ml, Area Under Curve (AUC)was 0.732 (95% CI 0.65-0.80, p 1.81 mg/dl, AUC was 0.787 (95% CI 0.71-0.85, p &lt; 0.001), sensitivity 53.19%, specificity 77.17%, positive predictive value 54.3%, negative predictive value 76.3%.Combined three biomarker plasma NGAL, Cystatin C and NT proBNP, the specificity of the diagnosis was the highest 95.6%, the positive predictive value was the highest 84.62% in diagnosing CRS1. Conclusions: The combined plasma NGAL, Cystatin C and NT-pro BNP is high value in the diagnosis of CRS1 in patients with AHF or ADHF.

Prognostic Association of Plasma NT-ProBNP Levels in Patients with Microvascular Angina - A Report from the International Cohort Study by COVADIS-

Prognostic Association of Plasma NT-ProBNP Levels in Patients with Microvascular Angina - A Report from the International Cohort Study by COVADIS-

The Clinical Noteworthiness of Plasma NT-ProBNP Standard in Sufferers with Cardiogenic Cerebral Embolism and Its Diagnostic Value for Such Sufferers.

In order to explore the clinical noteworthiness of plasma NT-proBNP standards in sufferers with cardiogenic cerebral embolism and its diagnostic value for such sufferers, a retrospective study is conducted by the clinical data of sufferers with cerebral embolism. 100 sufferers with cerebral embolism admitted to our hospital from January 2018 to December 2020 are selected. According to the heparin-like drug therapy of acute ischemic stroke test (TOAST) classification criteria, they are divided into cardiac sufferers with cerebral embolism set (43 cases) and noncardiac cerebral embolism set (57 cases). The analysis results show the correlation between serum NT-proBNP standard and neurological impairment score. The detection of-proBNP standard can be used as a diagnostic indicator of disease severity and prognosis for sufferers with cardiogenic cerebral embolism.

Abstract 13834: The Effect of Dapagliflozin on Serum Uric Acid in Heart Failure With Reduced Ejection Fraction: Insights From DAPA-HF

Introduction: Elevated serum uric acid (sUA) levels are common in patients with heart failure and reduced ejection fraction (HFrEF). sUA, in part, reflects the use of diuretics, and higher sUA is associated with a higher risk of adverse outcomes in HFrEF. We examined the effect of dapagliflozin on sUA, and the efficacy of dapagliflozin according to baseline sUA, in the Dapagliflozin and Prevention of Adverse Outcomes in Heart Failure (DAPA-HF) trial. Methods: Patients in NYHA class II-IV with a LVEF ≤40%, and elevated plasma NT-proBNP were included in DAPA-HF. Key exclusions included hypotension, systolic BP &lt;95 mmHg, and eGFR &lt;30 ml/min/1.73m 2 . The primary outcome was a composite of worsening HF (hospitalization for HF or an urgent HF visit requiring iv therapy) or CV death. sUA was measured pre-randomization and at 52 weeks. The effect of dapagliflozin on sUA was assessed using a linear regression model adjusted for baseline value. The efficacy of dapagliflozin was assessed using baseline sUA as a continuous variable. Results: Of the 4744 randomized patients, 3119 (65.7%) had sUA measured at baseline, with a mean of 6.10±1.70 (median 5.9, IQR 4.9-7.1) mg/dL. The placebo-corrected change in sUA at 52 weeks was -0.83 mg/dL (95% CI -0.93, -0.74); p&lt;0.001.In adjusted models including diuretic use/dose, higher sUA was associated with an elevated risk of the primary endpoint; hazard ratio 1.09 (1.03-1.14) per 1mg/dL sUA; p=0.0015 Figure, Panel A .The benefit of dapagliflozin, compared with placebo, on the primary endpoint was consistent across the range of sUA studied ( Figure, Panel B ; P interaction=0.77). Conclusions: In DAPA-HF, higher sUA was associated with worse outcomes and dapagliflozin significantly reduced sUA. The efficacy of dapagliflozin on outcomes was consistent across the range of sUA studied.

Abstract 13569: A Composite Score Summarizing Use And Dosing Of Evidence-based Medical Therapies In Heart Failure: Application To The DAPA-HF Trial

Introduction: The Heart Failure Collaboratory consortium (HFC) has developed a score to quantify background guideline-directed medical therapy (GDMT) in patients with heart failure and reduced ejection fraction (HFrEF). One potential use of this score is to test the incremental value of new therapies. We evaluated the effect of dapagliflozin according to a modified HFC score in the DAPA-HF trial. Methods: The key inclusion criteria in DAPA-HF were: 1) NYHA class II-IV, 2) LVEF ≤40%, and 3) elevated plasma NT-proBNP and 4) eGFR ≥30 ml/min/1.73m2. The primary outcome was a composite of a first episode of worsening HF (hospitalization for HF or an urgent HF visit requiring iv therapy) or cardiovascular death. The HFC score is calculated based on the use of GDMT and dose of GDMT. The modified HFC score used here also accounted for race (Black/non-Black) and ECG rhythm/rate with a maximum possible score of 100 (percent) for any patient (Panel A). Results: Among the 4744 patients (mean age 66 years; 23% women) randomized, an ACEi/ARB was used in 84%, beta-blocker 96%, MRA 71%, ARNI 11%, ivabradine 4.8%, and hydralazine 4.3%. During a median follow-up of 18.2 months, the primary outcome occurred in 386 of 2373 patients (16.3%) in the dapagliflozin group and 502 of 2371 patients (21.2%) in the placebo group (HR, 0.74; 95%CI 0.65 to 0.85; P&lt;0.001). The benefit of dapagliflozin on the primary outcome was consistent across the range of baseline treatment score (Panel B). Examination of the effect of dapagliflozin on the primary outcome by score tertile (T1 ≤40, T2 41-60 and T3 &gt;60) gave HRs for the effect of dapagliflozin, compared with placebo, of 0.75 (0.61-0.93), 0.77 (0.61-0.98), and 0.71 (0.55-0.90), respectively (P-interaction 0.87). Conclusions: A composite score for GDMT of the type developed by the HFC can be easily calculated in clinical trials and used to evaluate the incremental effect of new therapies.