proBNP Concentrations Research Articles

Evaluation of Urolithin A Efficacy in Heart Failure Patients with Reduced Ejection Fraction: A Randomized, Double-blind, Crossover, Placebo-controlled Clinical Trial.

Mitochondrial dysfunction and impaired mitophagy are integral to myocyte loss and the progression of heart failure. Urolithin A (UA), a microbiota-produced metabolite of ellagitannins and ellagic acid, is a known stimulator of mitophagy and mitochondrial biogenesis that has shown cardioprotective effects in experimental models. A randomized, double-blind, placebo-controlled 2×2 crossover trial was conducted on 10 patients with HF with reduced ejection fraction (HFrEF). The trial design involved two 4- week intervention periods of UA (500 mg BID) and placebo, separated by a 2-week washout phase. The patients underwent two-dimensional echocardiogram examination as well as blood sampling at the beginning and end of each period. All patients completed the study. The results failed to reveal any significant effect of UA supplementation on echocardiographic measures (LVEF, LVEDD, LVESV, and TAPSE). Plasma concentrations of pro-BNP, glucose, and CRP (p >0.05) were also not altered. Serum HDL-C levels were increased with UA compared with placebo (+6.46 ± 2.33 mg/dL, p =0.026), whereas other lipid indices (LDL-C, triglycerides, total cholesterol, and VLDL-C) remained unchanged (p >0.05). The results of the present study do not support any positive effect of UA supplementation in improving echocardiographic and biochemical indices of HFrEF. Further studies with higher doses of UA and longer supplementation duration are encouraged to be conducted.

A study of size-selective renal elimination using a novel human model

The recently discovered selective glomerular hypofiltration syndromes have increased interest in the actual elimination of molecules in the human kidney. In the present study, a novel human model was introduced to directly measure the single-pass renal elimination of molecules of increasing size. Plasma concentrations of urea, creatinine, C-peptide, insulin, pro-BNP, β2-microglobulin, cystatin C, troponin-T, orosomucoid, albumin, and IgG were analysed in arterial and renal venous blood from 45 patients undergoing Transcatheter Aortic Valve Implantation (TAVI). The renal elimination ratio (RER) was calculated as the arteriovenous concentration difference divided by the arterial concentration. Estimated glomerular filtration rate (eGFR) was calculated by the CKD-EPI equations for both creatinine and cystatin C. Creatinine (0.11 kDa) showed the highest RER (21.0 ± 6.3%). With increasing molecular size, the RER gradually decreased, where the RER of cystatin C (13 kDa) was 14.4 ± 5.3% and troponin-T (36 kDa) was 11.3 ± 4.6%. The renal elimination threshold was found between 36 and 44 kDa as the RER of orosomucoid (44 kDa) was −0.2 ± 4.7%. The RER of creatinine and cystatin C showed a significant and moderate positive linear relationship with eGFR (r = 0.48 and 0.40). In conclusion, a novel human model was employed to demonstrate a decline in renal elimination with increasing molecular size. Moreover, RERs of creatinine and cystatin C were found to correlate with eGFR, suggesting the potential of this model to study selective glomerular hypofiltration syndromes.

Impact of Adaptive Servo-Ventilation in Heart Failure Patients

Objective: Sleep-related breathing disorders (SRBD) as obstructive apnea, central apnea, and Cheyne-Stokes respiration (CSR), can be seen in patients with chronic heart failure. SRBD can influence the prognosis of heart failure. We aim to reveal sleep-related breathing disorders in heart failure patients and display the effects of adaptive servo-ventilation (ASV) as a new therapeutic modality. Materials and Methods: In this prospective study, 32 patients with heart failure were included. One night polysomnography (PSG) was done. Results: According to the results of PSG, the SRBD ratio was 96.7%. Continuous positive airway pressure (CPAP) and ASV titrations were offered to all patients with an apnea-hypopnea index (AHI) > 5. Demographics, clinical properties, symptoms, PSG findings, Cheyne-Stokes respiration (CSR), and echocardiography results were recorded. Before and after ASV titration, pulmonary function tests and walking tests were performed, and concentrations of transferrin and pro-BNP were recorded. In the groups according to the AHI, severe obstructive sleep apnea syndrome (OSAS) in 18 of 30 patients, four moderate OSAS, five mild OSAS, and two central sleep apnea (CSA). PSG and, CPAP, ASV titrations were done in 7 male and one female patient that obstructive apnea, central apnea, AHI, arousal, and SpO2 min values had significant improvements (p=0,001, p=0,016, p=0,001, p=0,015 and p=0,008 respectively). We determined all CSRs were eliminated with ASV. After ASV titration pro-BNP, walking distance, and FVC values changed significantly (p=0,036, p=0,018, and p=0,018 respectively). Conclusion: As a result, we determined CSR and central apneas persisted with CPAP but were eliminated with a one-night ASV application. ASV also decreased pro-BNP and increased FVC and walking distance values significantly.

New reference limits for cardiac troponin T and N-terminal b-type natriuretic propeptide in elders

Background and aimsOur aim was to define reference limits for cardiac troponin T (cTnT) and N-terminal pro B-type natriuretic peptide (proBNP) that would better reflect their concentrations in older people. In addition, the incidence of acute myocardial infarctions (AMIs) was studied using these reference limits in an older population with and without previous heart diseases. Materials and methodsA population-based study with a ten-year follow-up. The reference population was formed by 763 individuals aged over 64 years, with no diagnoses of heart or kidney diseases. ResultsThere was a significant increase in cTnT and proBNP concentrations with age. The 99 % reference limits for cTnT were 25 ng/L, 28 ng/l, 38 ng/l, and 71 ng/l for men in five-year-intervals starting from 64 to 69 years to 80 years and older, and 18 ng/L, 22 ng/l, 26 ng/l, and 52 ng/L for women, respectively. The 97.5 % reference limits for proBNP were 272 ng/L, 287 ng/l, 373 ng/l and 686 ng/L for men, and 341 ng/L, 377 ng/l, 471 ng/l, and 794 ng/L for women, respectively. Elevated proBNP was statistically significantly associated with future AMIs in subjects with and without a previous heart disease. ConclusionsAge-specific reference limits for cTnT and proBNP are needed to better evaluate cardiac symptoms.

Clinical effect of renal dysfunction on diagnostic and prognostic accuracy of B-type Natriuretic Peptide and N-terminal Pro-B-type Natriuretic Peptide for acute heart failure

Abstract Background Acute heart failure (AHF) continues to have unacceptable high rates of mortality and morbidity. Therefore, accurate and rapid diagnosis of AHF is crucial for the early initiation of effective treatment. Previous studies have shown that plasma concentrations of B-type natriuretic peptide (BNP) and N-terminal pro-BNP (NT-proBNP) increase with declining renal function and that renal dysfunction seems to decrease the accuracy of BNP and NT-proBNP in the diagnosis of AHF. Purpose We aimed to directly compare the diagnostic and prognostic accuracy of BNP and NT-proBNP in patients presenting with acute dyspnea, including the effect of renal function. Methods This prospective diagnostic study enrolled unselected patients presenting with acute dyspnea to the emergency department. The final diagnosis was centrally adjudicated by two independent cardiologists using all information including imaging and follow-up. BNP and NT-proBNP plasma levels were determined at presentation. 360 days all-cause mortality was the primary prognostic end point. Results Among 1579 patients, acute heart failure (AHF) was the adjudicated final diagnosis in 865 patients (54.8%). Plasma concentrations of both BNP and NT-proBNP were significantly higher in AHF as compared to other causes of acute dyspnea (both p<0.001). Diagnostic accuracy as quantified by the area under the receiver-operating-characteristics curve (AUC) was 0.948 (95% CI 0.938-0.958) for BNP as compared to 0.921 (95% CI 0.908-0.935) for NT-proBNP, p<0.001. The diagnostic superiority of BNP was consistent among predefined subgroups according to renal function and increased with the extent of renal dysfunction (Figure 1: all patients (A), patients with eGFR≥ 60 ml/min/1,73 m² (B), patients with eGFR 30-59 ml/min/1,73 m² (C), patients with eGFR <30ml/min/1,73 m² (D)). In contrast, prognostic accuracy for the prediction of death at 360 days was higher for NT-proBNP (AUC 0.731, 95% CI 0.702-0.760 versus 0.706, 95%CI 0.676-0.736 for BNP; p<0.001). The diagnostic superiority of NTproBNP was consistent among predefined subgroups according to renal function but decreased with the extent of renal dysfunction. Conclusion In patients with acute dyspnea, BNP and NT-proBNP at presentation both have very high diagnostic accuracy for AHF and moderate prognostic accuracy for death. There is a numerically small, but statistically and possibly also clinically significant diagnostic superiority of BNP and prognostic superiority of NT-proBNP.Diagnostic accuracy for AHF

#3115 THE ASSOCIATION OF FIBROBLAST GROWTH FACTOR-23 AND CARDIORENAL SYNDROME IN PATIENTS WITH DIABETES MELLITUS

Abstract Background and Aims Previous studies suggest that interactions between the heart and the kidney can contribute to the progressive dysfunction of both organs. Recently, there has been an increase in the prevalence of cardiovascular disease (CVD) and chronic kidney disease (CKD) due to increasing diabetes mellitus rate. It is known that fibroblast growth factor-23 (FGF-23) has been found to be related to kidney metabolism especially as a biomarker and a key factor to be used in the kidney field. The aim of our study was to assess potential therapeutic approaches of the use of FGF-23 in clinical settings as a potential circulating biomarker for CVD and CKD. Method A total of 155 patients with DT2, aged 34 to 84 years (60 [60;72]), were examined. Control group included 94 healthy people the same age. All patients underwent standard clinical and laboratory examination, with an assessment of the levels of FGF-23 in baseline plasma samples. Renal function was assessed based on the levels of serum creatinine, cystatin C, eGFR, which was calculated according to the CKD-EPI formula, and albuminuria, which was assessed as albumin/creatinine ratio (A/C). An echocardiographic examination was conducted according to the standard protocol with the calculation of dimensional, volume and speed characteristics. Results The levels of FGF-23 were significantly higher in DT2 patients with CKD 5 in comparison with stages 1–4. There were positive strong significant association between FGF-23 and creatinine (r = 0.71, p<0.001). In both unadjusted and adjusted analyses, probability of decreased eGFR was associated strongly with FGF-23 (COR; 95% CI 1.890; 1.362-2.622, p<0,001). When evaluating the dependence of the probability of decreased eGFR on the FGF-23 using the ROC analysis, the cut-off value of FGF-23 was 0,9 pmol/l. The sensitivity and specificity of the method were 75.3% and 74.5%, respectively (AUC 0.832±0.035 with 95% CI: 0.764-0.901, p<0.001). DT2 patients with left ventricular hypertrophy (LVH) were characterized by higher levels of FGF-23 (2,45 [0,65;7,43] vs 0,57 [0,19;2,19] pmol/l in control group). DT2 patients with LVH and natriuretic peptides levels ≥ 35 pg/ml for BNP and/or ≥125 ng/ml for NT-proBNP had significantly high concentrations of FGF-23 than patients with normal levels of natriuretic peptides (3,22 [1,09;9,55] vs. 0,52 [0,27;1,08] pmol/l, p<0,0001). In order to assess the diagnostic significance of the FGF-23 for predicting left ventricular mass index (LVMI) thickening and increasing the proBNP concentration, a ROC analysis was performed. Thus, at the level of FGF-23 (AUC-0.702) = 0.9 pmol/l, the sensitivity and specificity for LVMI thickening were 66.9% and 67.3%. Conclusion Our study identifies FGF-23 as a promising target of novel therapeutic interventions in cardiorenal syndrome, which should be investigated in future clinical studies.

C28 LEFT VENTRICULAR OUTFLOW TRACT VELOCITY–TIME INTEGRAL (LVOT–VTI) IMPROVES RISK STRATIFICATION IN HEART FAILURE PATIENTS WITH SECONDARY MITRAL REGURGITATION

Abstract Background Reduced left ventricular ejection fraction (LVEF) has been used as a key criterion for the management of mitral regurgitation (MR) in patients with heart failure (HF), including the decision about mitral valve repair. However, LVEF, not taking into account mitral regurgitant volume, may be an imprecise predictor of outcome in HF patients with MR. Conversely, the estimation of the forward volume through the LV outflow tract (LVOT) may be a better metric in this setting. In this regard, LVOT velocity time integral (LVOT–VTI), not relying on geometrical assumptions, has been shown to be more reproducible than the calculated stroke volume (i.e., LVOT–VTI * LVOT cross sectional area). Objective To assess the prognostic significance of LVOT–VTI in a contemporary cohort of patients with chronic HF and significant MR. Methods Consecutive patients with chronic HF with reduced (≤40%) or mildly reduced (41–49%) LVEF and moderate–to–severe or severe MR, according to the latest European Society of Cardiology criteria, were selected and followed–up for the endpoint of cardiac death. Results 287 patients were enrolled in the study (74±11 years, 70% men, 46% ischemic etiology, HFrEF 89%, LVEF 30±9%, mean LVOT–VTI 20±5 cm). Most patients showed a NYHA class II (40%) or III (31%) and received beta–blockers (93%), ACE–inhibitors/ARBs or ARNI (77%), and mineralocorticoid receptor antagonists (76%). One hundred and ten patients (39%) had permanent atrial fibrillation and 82 (29%) a cardiac resynchronization therapy device. Over a median follow–up of 33 (16–47) months, 114 patients died, 71 of whom for cardiac cause, and 28 underwent mitral valve repair/replacement. The risk of cardiac death increased proportionally to the decrease of LVOT–VTI (Figure 1, panel A), with an optimal prognostic cut–off of 17 cm (Figure 1, panel B). Reduced LVOT–VTI was associated with higher NYHA class, NT–proBNP concentration, and worse right ventricle systolic function (all p<0.005). At multivariable competing risks regression analysis, a unit decrease of LVOT–VTI (HR 0.87 [95%CI 0.80–0.93], p<0.001), but not of LVEF (p=0.254), was independently associated with a higher risk of cardiac death (Figure 1, panel C). Conclusion Left ventricular forward volume, noninvasively estimated through LVOT–VTI, but not LVEF, predicts the risk of cardiac death in patients with chronic HF and significant MR.

Multicolored MIS-C, a single-centre cohort study

BackgroundThe aim of this study was to investigate the clinical and laboratory parameters that can predict the severity of Multisystem Inflammatory Syndrome in Children (MIS-C) at admission.MethodsWe conducted a single-center, partly retrospective, partly prospective, observational cohort study between November 1, 2020 and December 31, 2021, which included patients aged from 1 month to 19 years, meeting the diagnostic criteria of MIS-C. We categorized the patients into three subgroups based on clinical and laboratory markers and assessed the predictive value of these factors in terms of ICU administration and cardiac abnormalities.Results53 patients were classified in the following subgroups: Kawasaki-like disease (group 1) (47.2%, n = 25), shock with or without acute cardiac dysfunction (group 2) (32%, n = 17), fever and inflammation (group 3) (20.8%, n = 11). Subgroup analysis revealed that patients with shock and KD at initial presentation had significantly more severe manifestation of MIS-C requiring intensive care unit (ICU) treatment. Of the initial laboratory values, only CRP showed a significant difference between the 3 clinical groups, being lower in group 3. 52.6% of patients were admitted to the ICU. The median length of ICU stay was 3 days (range 3–20). ICU admission was more likely in patients with shortness of breath, renal failure (AKI) and patients with significantly increased concentrations of ferritin, D-dimer, INR and significantly milder increase concentration of fibrinogen. We found that fibrinogen and ferritin levels are independent risk factors for ICU admission. Cardiac abnormalities were found in 56.6% of total (30/53), with the following findings: decreased left ventricular function (32%), coronary abnormality (11.3%), pericardial effusion (17%), arrhythmia (32.1%) and mitral regurgitation (26.6%). Diarrhea and conjunctivitis at the initial presentation with significantly elevated CRP, Pro-BNP and blood pH concentrations were found to be a potential predisposing factor for decreased cardiac function while Pro-BNP and pH were independent risk factors for MIS-C. Regardless of the initial symptoms of MIS-C, the outcome was generally favorable.ConclusionsClinical characteristics and baseline laboratory values ​​may help identify patients at increased risk for severe disease outcome, such as need for intensive care, presence of shock and decreased cardiac function.Trial registrationParticipation consent was not reqired and ethical considerations were unnecessary, since we did not perform any extra interventions, only the necessary and usual therapeutic and diagnostic methods were used.

Prevalence and characteristics of newly diagnosed heart failure in patients with shortness of breath after coronavirus infection

Aim. To determine the prevalence and show the features of the development of newly diagnosed heart failure (HF) in patients with dyspnea after a coronavirus disease 2019 (COVID-19).Material and methods. This clinical prospective observational study was conducted during 2020-2022. The study consecutively included 368 outpatients with shortness of breath, who applied to the clinic. Depending on the presence of prior COVID-19, the patients were divided into 2 groups: the first group consisted of 205 patients with shortness of breath after COVID-19, the second group — 163 patients without prior COVID-19. All patients underwent a clinical examination within 3 days after presentation with an assessment of outpatient records and other medical documents for the differential diagnosis of dyspnea. The severity of dyspnea was determined using the Modified Medical Research Council Dyspnoea Scale (mMRC). The diagnosis of HF was verified in accordance with the 2020 Russian Society of Cardiology guidelines and in some cases reclassified in accordance with the 2021European Society of Cardiology guidelines. For further analysis, 2 subgroups of patients with HF were identified depending on the presence and absence of prior COVID-19. The subgroup analysis excluded patients with acute heart failure, acute illness, and conditions requiring hospitalization and/or intensive care.Results. Among 368 patients who presented to the clinic with dyspnea during 2020-2022, 205 patients (55,7%) had COVID-19. The average period of treatment after COVID-19 was 3,5 [1,5; 22,4] months. Patients after COVID-19 applied earlier after the onset of dyspnea, which is associated with higher mMRC score. The prevalence of HF among patients with shortness of breath after COVID-19 was significantly higher than in patients without this pathology in history, and amounted to 19,0% vs 9,8% (p=0,021). Prior COVID-19 increased the relative risk (RR) of HF in patients with shortness of breath by 1,7 times. RR for HF in systolic blood pressure >140 mm Hg increased by 1,9 times, while in diastolic blood pressure >90 mm Hg — by 1,9 times, with the development of a hypertensive crisis — by 28%, with a heart rate >80 bpm at rest — by 1,4 times, with the development of type 2 diabetes — by 31%, in the presence of pulmonary fibrosis — by 2,3 times. Patients with shortness of breath after COVID-19 had more severe HF, both according to clinical tests and according to the blood concentration of N-terminal pro-brain natriuretic peptide (NT-proBNP), mainly with the preserved ejection fraction (EF) with a higher prevalence of left atrial (LA) enlargement in combination with a decrease in right ventricular (RV) systolic function and its dilatation. In patients after COVID-19 in the presence of chronic kidney disease, the RR for HF increased by 4,5 times; in the presence of C-reactive protein >4 mg/l — by 1,6 times.Conclusion. Every fifth patient with shortness of breath 3,5 months after COVID-19 had more severe HF, both according to clinical tests and according to blood NT- proBNP concentration, mainly with preserved EF with a higher prevalence of LA increase in combination with a decrease in RV systolic function and its dilatation. The risk of HF is interrelated with the female sex and multiple comorbidities.

Markers of bone metabolism are associated in all-cause mortality in heart failure with reduced ejection fraction

Abstract Background In patients with heart failure an increased risk of fracture-related mortality has been reported. A growing body of evidence suggests that, heart failure (HF) itself may be related to disturbances in bone metabolism, but the exact mechanism remains unclear. In patients with HF previous studies indicated a loss of renal function and alterations in bone micro-architecture, but the clinical relevance remains unclear. Purpose We aimed to evaluate the association between markers of bone metabolism with mortality and pro-brain natriuretic peptide (proBNP) in patients with HF with reduced ejection fraction (HFrEF). Methods We analysed participants of a prospective cohort study of patients referred to coronary angiography (CA). The baseline examination was performed at a tertiary care centre in Germany. Indications for CA were based on clinical routine. For the current analysis only patients with HFrEF were included. Patients were selected based on echocardiographic left ventricular (LV)-EF≤40%, symptoms of heart failure and elevated proBNP concentrations, as recommended by current clinical guidelines. We estimated the risk associated with parathyroid hormone (PTH), osteocalcin (OC), beta-crosslaps (βCL) and alkaline phosphatase (AP) and all-cause mortality using Cox proportional hazard models. Adjustments for demographic and clinical characteristics from the index hospital presentation were used as covariates. We included all individuals who had complete data for all variables in the study in our primary analysis. Additionally, we used linear regression analysis to investigate the correlation between proBNP and its association with PTH, OC, βCL and AP. Results A total of 297 participants (63.9±9.9 years; 17.9% females) were included in the analysis. Median follow-up was 10 years. Median LV-EF was 35%, median New York Heart Association functional class was 2 (IQR=1–3), mean pulmonary capillary wedge pressure was 15.3±7.4 mmHg and median proBNP levels of 2282 (IQR 1875–3758) ng/ml. Participants had in 42.3% multi-vessel atherosclerotic CAD (with stenosis of ≥50% considered diagnostic) with 66.4% had a previous myocardial infarction. In multivariate cox proportionate hazard models OC, βCL and AP were statistically significant associated with an increased risk for all-cause mortality (hazard ratio (HR)=1.6 [95% CI 1.2–2.2], HR=1.8 [95% CI 1.1–2.9] and HR=2.1 [95% CI 1.5–2.9], respectively). In multivariate analysis proBNP was associated with PTH (β-coefficient = 0.076; P≤0.001), AP (β-coefficient = 0.125; P=0.001) and βCL (β-coefficient = 0.062; P=0.046), but not with osteocalcin (β-coefficient = −0.055; P=0.145). Conclusion In patients with HFrEF markers of bone metabolism were significantly associated with mortality and proBNP concentrations. Future studies should focus on different aspects of bone metabolism, fracture rates and fracture related mortality in patients with different stages of heart failure. Funding Acknowledgement Type of funding sources: None.

2D Echocardiographic Findings, NT-ProBNP Levels, and Outcomes in Dyspnoeic Patients: Results from the Pro-BNP Investigation of Dyspnoea in the Emergency Department- a Single Centre Experience

Background: Dyspnoeic in the emergency department with multiple co-morbidities is a diagnostic challenge. Approximately 15-20% of acute dyspneic in the Emergency Department due to ADHF (acute decompensated heart failure) are misdiagnosed. B-type peptide (BNP) and its amino-terminal fragment (NT-proBNP) accurately identify HF in dyspnoeic patients. In the general population with dyspnoea, plasma pro-BNP concentrations are increased in left ventricular dilatation, hypertrophy, systolic dysfunction, or diastolic dysfunction but are unaffected by pulmonary dysfunction.
 Aims and Objectives: To study the relation between NT pro-BNP & echocardiographic findings in acute dyspnoeic patients, and the relation between NT pro-BNP and In-hospital Mortality.
 Materials and Methods: Source of data- Patients admitted to the Emergency Room or cardiac intensive care unit with a history of acute dyspnea in a tertiary cardiac care center in south India, meeting inclusion & exclusion criteria, were studied.
 Results: The study population is predominantly constituted of the elderly population. The most common co-morbid condition was hypertension. The present study uses an NT pro BNP level of 900pg/ml as the cut-off level. 78 patients were positive for the test. Echocardiography showed that 58% had LV systolic dysfunction, 60% had diastolic dysfunction. 42 patients had EF >55%, 10 patients between 55-45%, 33 patients between 44-30% and 15 patients had EF < 30%. Mortality rate was 6% in the whole study population. However, Mortality was seen in only NT pro-BNP positive group it was not statistically significant (p=0.46).
 Conclusions: NT pro-BNP correlates well with the worsening of LV systolic function; as the EF decreases, NT pro-BNP increases. Increase in NT pro-BNP levels has to be interpreted in the clinical context, and it is not a substitute for echocardiography for assessing cardiac abnormalities and dysfunction.

The Evaluation of Functional Abilities Using the Modified Fullerton Functional Fitness Test Is a Valuable Accessory in Diagnosing Men with Heart Failure

The assessment of functional abilities reflects the ability to perform everyday life activities that require specific endurance and physical fitness. The Fullerton functional fitness test (FFFT) seems to be the most appropriate for assessing physical fitness in heart failure (HF) patients. The study group consisted of 30 consecutive patients hospitalized for the routine assessment of HF with a reduced ejection fraction (HFrEF). They formed the study group, and 24 healthy subjects formed the control group. Each patient underwent a cardiopulmonary exercise test (CPET), transthoracic echocardiography and FFFT modified by adding the measurement of the handgrip force of the dominant limb with the digital dynamometer. The HF patients had significantly lower peak oxygen uptake (peakVO2), maximal minute ventilation, and higher ventilatory equivalent (VE/VCO2). The concentrations of B-type natriuretic peptide (BNP) and N-terminal proBNP (NT-proBNP) were significantly higher in the study group. The results of all the FFFT items were significantly worse in the study group. FFFT parameters, together with the assessment of the strength of the handgrip, strongly correlated with the results of standard tests in HF. FFFT is an effective and safe tool for the functional evaluation of patients with HFrEF. Simple muscle strength measurement with a hand-held dynamometer can become a convenient and practical indicator of muscle strength in HF patients.

The role of ProBNP in differentiation of cardiogenic and non-cardiogenic syncope: A diagnostic accuracy study

Objective: The significance of diagnosing the root reason for syncope and taking the required preventive or treatment measures cannot be overlooked when it comes to outcome prediction. This study endeavors to examine the role of proBNP in differentiating cardiogenic and non-cardiogenic syncope in patients presenting to the emergency department (ED). Methods: We prospectively performed a cross-sectional study on patients presenting with acute syncope. All the patients for this investigation were followed up until the definite cause of their syncope (cardiac or non-cardiac) was diagnosed and the screening performance characteristics of proBNP in differentiation of cardiogenic and non-cardiogenic syncope were evaluated. Results: Three hundred patients with syncope were studied (64.7% male). In the end, the cause of syncope was determined to be cardiogenic in 133 cases (44.3%). The area under the ROC curve of proBNP in the differentiation of cardiogenic syncope from non-cardiogenic was estimated to be 78.9 (95% CI: 73.5 – 84.3). The optimal cut-off point for proBNP in this regard was 143.5 pg/mL point. Sensitivity, specificity, positive and negative predictive values, and positive and negative likelihood ratios of proBNP in the mentioned cut-off point were 75.39% (95% CI: 67.61–82.73), 75.44% (95% CI: 68.07–81.62), 71.12% (95% CI: 62.82–78.26), 79.74% (95% CI: 72.46–85.54), 2.46 (95% CI: 1.86–3.25), and 0.25 (95% CI: 0.18–0.34), respectively. Conclusion: The accuracy of proBNP in differentiation of cardiogenic and non-cardiogenic syncope is fair. ProBNP concentration equals to or higher than 143.5 pg/mL can differentiate cardiogenic syncope from non-cardiogenic with 75% sensitivity and 76% specificity. It seems that its use for this purpose should be considered with caution and along with other tools.

Cardio-protective effect of dapagliflozin against doxorubicin induced cardiomyopathy in rats.

Cancer is the second most common non-communicable disease group in the world and its frequency is increasing. In parallel, side effects of drugs used in cancer treatment are frequently encountered. Doxorubicin (DOX) is one of the most effective multi-purpose anticancer drugs. However, its use is significantly limited due to the risk of cardiotoxicity. Sodium-glucose cotransporter-2 inhibitors are a group of antidiabetic drugs that have been shown to reduce cardiovascular events. Our aim is to examine the preventive effect of dapagliflozin on DOX-induced cardiac damage. We used 30 albino rats. 20 of 30 rats were administered doxorubicin for cardiomyopathy model. The rats in the DOX arm were divided into two groups: those given penicillin and placebo. After the rats were terminated, tissues were prepared for histopathological and immunohistochemical examination. TNF-α, pro-BNP, troponin T and plasma FGF-21 levels were also measured in plasma. The mean concentrations of cTnT and pro-BNP in the plasma of the DOX treated rats demonstrated a significantly higher value compared to the control group. Treatment with dapagliflozin caused a significant reduction in plasma cTnT, pro-BNP and TNF-α levels concentrations compared to the DOX control group (p < 0.001). The group of rats treated with dapagliflozin was effective in significantly decreasing the FGF-21 concentration and the percentage of fibronectin immunoexpression compared to the DOX control group (p < 0.0001). This study revealed, for the first time, that dapagliflozin can improve DOX-induced cardiac dysfunction and pathological changes in non-diabetic rats. This result has shown that dapaglifozin, may be promising in terms of preventing cardiac damage that may develop in cancer treatment.

Quality Indicators in Patient Referral Documents for Heart Failure in Japan.

This study examined quality indicators (QIs) for heart failure (HF) in patients' referral documents (PRDs).We conducted a nationwide questionnaire survey to identify information that general practitioners (GPs) would like hospital cardiologists (HCs) to include in PRDs and that HCs actually include in PRDs. The percentage of GPs that desired each item included in PRDs was converted into a deviation score, and items with a deviation score of ≥ 50 were defined as QIs. We rated the quality of PRDs provided by HCs based on QI assessment.We received 281 responses from HCs and 145 responses from GPs. The following were identified as QIs: 1) HF cause; 2) B-type natriuretic peptide (BNP) or N-terminal pro-BNP concentration; 3) left ventricular ejection fraction or echocardiography; 4) body weight; 5) education of patients and their families on HF; 6) physical function, and 7) functions of daily living. Based on QI assessment, only 21.7% of HCs included all seven items in their PRDs. HCs specializing in HF and institutions with many full-time HCs were independently associated with including the seven items in PRDs.The quality of PRDs for HF varies among physicians and hospitals, and standardization is needed based on QI assessment.

Abstract P154: Reliability Of Cardiovascular Disease Surveillance In The National Longitudinal Study Of Adolescent To Adult Health

Background: Young to middle-aged U.S. adults are burdened by the obesity, opioid, and COVID-19 epidemics. However, the ability to detect cardiovascular disease (CVD) manifestations of population-wide changes in risk factors within contemporary cohorts in young to middle adulthood is unknown. Objective: To assess inter-rater reliability of death certificate (DC), obituary, coroner/medical examiner (CME) autopsy report, and hospital record abstraction in young to middle adulthood. Setting: The National Longitudinal Study of Adolescent to Adult Health (Add Health), a nationally representative school-based sample of 20,745 U.S. adolescents in grades 7-12 (1994-1995) followed for the last 26 years and aged 37-45 years in 2020. Methods: We traced all participants, identified decedents, then collected DCs, obituaries, CME autopsy reports, and hospital records ≤ 1 month before death dates. Among a random sample of 28 decedents and an oversample of 28 hospitalized decedents enriched 3:1 for CVD, two trained and certified staff used an electronic data entry system to abstract data needed for outcome classification from the four information sources following standardized, item-by-item instructions. We measured item-specific reliability of categorical data abstraction as the agreement between abstractors (%) and prevalence- and bias-adjusted kappa coefficient ( PABAK ). We measured reliability of interval-scale data (e.g. creatinine; troponin; creatinine kinase; CK-MB; pro-BNP concentrations) as an intra-class correlation coefficient (ICC). Results: We identified 578 (2.8%) participants who were deceased through December 2020. Of those, 577 (99.8%) had high scoring National Death Index matches uniquely identifying decedents in 44 U.S. states. We collected and abstracted 531 (92%), 445 (77%), 178 (66%), and 95 (39%) of their DCs, obituaries, CME autopsy reports, and hospital records. CVD was the underlying cause of death in 10% (95% confidence interval [CI]: 8%-13%) of decedents. Mean, item-specific agreement (95% CI) was 0.86 (0.84-0.89), 0.90 (0.87-0.93), 0.93 (0.92-0.95), and 0.94 (0.92-0.95) for each source. The corresponding mean, item-specific PABAK (95% CI) was 0.83 (0.80-0.86), 0.86 (0.83-0.90), 0.92 (0.90-0.94) and 0.91 (0.89-0.93). The mean, biomarker-specific ICC (95% CI) was 0.96 (0.95-0.98). Conclusion: Overall, CVD was a major cause of mortality and reliability of abstraction was excellent across a range of measures. Ongoing investigation of deaths, and as needed, targeted staff retraining and improvement of abstraction protocol will enable high quality studies of CVD emergence within this large, nationally representative U.S. cohort. Such studies will provide generalizable insight into the biological mechanisms underlying cardiovascular manifestations and thereby inform understanding of changing CVD burden in the U.S. population.

Do more specific assays for B-type natriuretic peptides better predict heart failure in breathless patients than the currently used assays?

Abstract Funding Acknowledgements Type of funding sources: Private grant(s) and/or Sponsorship. Main funding source(s): Heart Foundation of New Zealand Health Research Council of New Zealand Introduction The cardioprotective B-type natriuretic peptide (BNP1-32) and its inactive congener N-terminal proBNP1-76 (NTBNP1-76) are produced from their precursor peptide proBNP, proportionate to cardiac dysfunction, underpinning their now-universal endorsement as markers for heart failure (HF) diagnosis. ProBNP concentrations are also increased in patients with HF. BNP1-32 is difficult to measure in plasma due to its low concentration and short half-life. Thus, less specific BNP and NT-proBNP assays are routinely used in the diagnosis and prognosis of HF. However, these assays also variably detect proBNP, BNP metabolites, and glycosylated proBNP or glycosylated NT-proBNP. How well these assays compare to highly specific assays that only detect BNP1-32 or NTBNP1-76 has not been assessed. Purpose We will compare the performance of assays specific for BNP1-32 and NTBNP1-76 only with that of a less specific commercially available NT-proBNP assay that is widely used for the diagnosis of heart failure. Methods Plasma samples obtained from patients presenting to the Emergency Department with breathlessness (n = 195) were assayed using a commercially available NT-proBNP assay and our specific in-house BNP1-32 (1) and NTBNP1-76 (2) assays. The diagnostic performance for clinically adjudicated acute HF (AHF, 60/195 patients, 31%) was assessed for each assay using receiver operator curve (ROC) analysis. Results Median (IQR) concentrations (n = 195) of NT-proBNP (101.7 [29.7, 353] pmol/L) and NTBNP1-76 (108.6 [25, 442] pmol/L) were markedly higher than BNP1-32 concentrations (1.9 [0.3-6.6] pmol/L) (p &amp;lt; 0.001 for both comparisons). Peptide concentrations were higher in patients with heart failure (n = 60) than those without heart failure for NT-proBNP (559 [247,1097] vs 46 [16,123] pmol/L), NTBNP1-76 (441.9 [155,1205] vs 37.9 [15,131] pmol/L) and BNP1-32 (7.8 [4,17] vs 0.5 [0.2,2.4] pmol/L) (all P &amp;lt; 0.001). NT-proBNP assay results were highly correlated with our specific NTBNP1-76 and BNP1-32 assays (Spearman’s rho = 0.91 and 0.92, respectively, both P &amp;lt; 0.001, n = 195). NT-proBNP, NTBNP1-76 and BNP1-32 assays performed similarly in the diagnosis of AHF (AUC [95%CI] = 0.88 [0.84-0.93], 0.85 [0.79-0.91] and 0.89 [0.84-0.94] respectively (all p &amp;lt; 0.001). Discussion Despite the differences in assay specificity all 3 assays performed similarly in the diagnosis of AHF in patients presenting with breathlessness. Conclusions All three assays diagnosed heart failure similarly, providing evidence that the widely used NT-proBNP assay can reliably be used as a proxy for active BNP1-32 in the diagnosis of acute heart failure. Whether this less specific NT-proBNP assay and our specific NTBNP1-76 and BNP1-32 assays (i) offer similar prognostic information and whether (ii) their marker performance is differentially altered by common confounders including age, renal dysfunction, obesity and atrial fibrillation, remain to be ascertained.

2-D material enhanced ultrasensitive electrochemical sensing of Pro-BNP peptide towards the risk-assessment of human heart

The high morbidity, mortality, and huge numbers of affected individuals have delineated cardiovascular diseases as one of the most vulnerable global health burdens. Amongst the top proteins to reflect ventricular dysfunction, Brain-type natriuretic peptide (BNP or ProBNP) carries substantial potential towards estimating human heart risk, both at the prognostic and diagnostic level. Herein, clinically significant concentrations of ProBNP ranging from 100 fg/mL to 100 ng/mL are assessed via a hydrothermally synthesized 2-D SnS2 nanomaterial enhanced ultrasensitive and selective portable electrochemical biosensor. X-ray Diffraction, Scanning Electron Microscopy, Transmission Electron Microscopy, and Fourier Transform Infra-Red Spectroscopy are performed for material characterization. The transduction mechanism is realized through the covalent immobilization of the target-specific antibodies on the bioelectrode surface. Multiplex trigger signals, i.e., cyclic voltammetry (CV), differential pulse voltammetry (DPV), and electrochemical impedance spectroscopy (EIS), are employed to explore the antigen-antibody binding event. The sensitivity of the proposed sensor is found to be 11.7355 (ΔR/R) (ng/mL)−1cm−2 in case of EIS and 103.2396 (ΔIp/Ip) % (ng/mL)−1cm−2 in case of DPV with the lowest limit of detection being 0.225 fg/mL (SNR=3.3) for 5 mg/mL SnS2-DMF dispersion. Further, it is subjected to interference, stability, selectivity, and recovery studies in PBS and plasma matrix aiming at the on-field diagnostic performance.

Study of Heart Rate Variability in Patients with Chronic Heart Failure and Chronic Obstructive Pulmonary Disease

Aim. To study heart rate variability (HRV) in patients with chronic heart failure (CHF) and chronic obstructive pulmonary disease (COPD) in relation to: blood oxygen saturation level, parameters of respiratory function (RPF), Nt – proBNP concentration in blood plasma.Materials and methods. We examined 128 outpatients of both sexes. The patients’ age ranged from 45 to 70 years. Group 1 – main (60 patients) with CHF of ischemic genesis of NYHA functional class II – III and GOLD COPD of I – III degree of airflow restriction (GOLD 2019 classification) in the stage of stable remission, group 2 – control group (63 patients), with isolated CHF. All patients with CHF, who were included in the study, had myocardial infarction (AMI) from 1 to 5 years ago. There were no statistically significant differences in the severity of CHF between groups 1 and 2.Results. In patients with CHF and COPD, in contrast to patients with isolated CHF, a significant prevalence of the frequency of occurrence of the hypersympathicotonic type of autonomic regulation was revealed. Significantly lower indicators of heart rate variability were in the group of patients with concomitant COPD in comparison with patients with isolated CHF. Statistically significant correlations were revealed between HRV parameters and RPF, parameters of blood oxygen saturation level, NT-proBNP concentration in blood. Multivariate regression analysis showed a significant dependence of HRV parameters on the parameters of HRV and the concentration of NT-proBNP in the blood in the group of patients with CHF and COPD.

Effect of various weight loss interventions on serum NT-proBNP concentration in severe obese subjects without clinical manifest heart failure

Obesity is associated with a “natriuretic handicap” indicated by reduced N-terminal fragment of proBNP (NT-proBNP) concentration. While gastric bypass surgery improves the natriuretic handicap, it is presently unclear if sleeve gastrectomy exhibits similar effects. We examined NT-proBNP serum concentration in n = 72 obese participants without heart failure before and 6 months after sleeve gastrectomy (n = 28), gastric bypass surgery (n = 19), and 3-month 800 kcal/day very-low calorie diet (n = 25). A significant weight loss was observed in all intervention groups. Within 6 months, NT-proBNP concentration tended to increase by a median of 44.3 pg/mL in the sleeve gastrectomy group (p = 0.07), while it remained unchanged in the other groups (all p ≥ 0.50). To gain insights into potential effectors, we additionally analyzed NT-proBNP serum concentration in n = 387 individuals with different metabolic phenotypes. Here, higher NT-proBNP levels were associated with lower nutritional fat and protein but not with carbohydrate intake. Of interest, NT-proBNP serum concentrations were inversely correlated with fasting glucose concentration in euglycemic individuals but not in individuals with prediabetes or type 2 diabetes. In conclusion, sleeve gastrectomy tended to increase NT-proBNP levels in obese individuals and might improve the obesity-associated “natriuretic handicap”. Thereby, nutritional fat and protein intake and the individual glucose homeostasis might be metabolic determinants of NT-proBNP serum concentration.