N-terminal Pro Natriuretic Peptide Research Articles

Myeloperoxidase and N-terminal proatrial natriuretic peptide as predictors for atrial fibrillation recurrence in patients undergoing redo ablation

BackgroundAtrial fibrillation (AF) is a progressively developing arrhythmia. Electroanatomic remodeling may play an important role, both in the development of the disease as well as in the perpetuation and thus in the recurrence of AF. ObjectiveThis study aimed to investigate potential biomarkers Myeloperoxidase (MPO), N-terminal pro-atrial natriuretic peptide (NT-proANP), intercellular adhesion molecule-1 (ICAM-1), and matrix metalloproteinase-2 (MMP-2) and their predictive value for AF recurrence in patients undergoing redo ablation. MethodsIn this single-center prospective cohort study 50 consecutive patients underwent ultra-high-density mapping and redo ablation. Biomarkers were determined before ablation and at 6 months follow-up. Seven-day Holter was conducted to check for AF recurrence (>30 seconds). ResultsEleven (22%) patients showed AF recurrence after redo ablation. ROC analysis revealed venous MPO and NT-proANP (AUC 0.755, 95% CI 0.599 – 0.912, p=0.010 and AUC 0.752, 95% CI 0.551 – 0.953, p=0.011) as acceptable predictors for intermediate AF recurrence, whereas MMP-2, ICAM-1, and established cardiovascular biomarkers such as NT-proBNP, Troponin T, and C-reactive protein were not (all AUC <0.600). MPO and NT-proANP correlated with AF burden (ρ 0.365, p=0.005 and ρ 0.362, p=0.005). While MPO was associated with atrial fibrosis in the endocardial map (ρ 0.280, p=0.024), NT-proANP correlated with left atrial volume index (ρ 0.256, p=0.037). There were no significant differences in biomarkers concentrations with regard to venous and coronary sinus samples. ConclusionMPO and NT-proANP are of predictive value for AF recurrence in patients undergoing redo ablation. While MPO correlated with endocardial fibrosis, NT-proANP was associated with left atrial volume.

Dapagliflozin and sacubitril on myocardial microperfusion in patients with post-acute myocardial infarction heart failure and type 2 diabetes.

Coronary heart disease and type 2 diabetes mellitus (T2DM) frequently coexist, creating a complex and challenging clinical scenario, particularly when complicated with acute myocardial infarction (AMI). To examine the effects of dapagliflozin combined with sakubactrovalsartan sodium tablets on myocardial microperfusion. In total, 98 patients were categorized into control (n = 47) and observation (n = 51) groups. The control group received noxital, while the observation group was treated with dapagliflozin combined with noxital for 6 months. Changes in myocardial microperfusion, blood glucose level, cardiac function, N-terminal prohormone of brain natriuretic peptide (NT-proBNP) level, growth differentiation factor-15 (GDF-15) level, and other related factors were compared between the two groups. Additionally, the incidence of major adverse cardiovascular events (MACE) and adverse reactions were calculated. After treatment, in the observation and control groups, the corrected thrombolysis in myocardial infarction frame counts were 37.12 ± 5.02 and 48.23 ± 4.66, respectively. The NT-proBNP levels were 1502.65 ± 255.87 and 2015.23 ± 286.31 pg/mL, the N-terminal pro-atrial natriuretic peptide (NT-proANP) levels were 1415.69 ± 213.05 and 1875.52 ± 241.02 ng/mL, the GDF-15 levels were 0.87 ± 0.43 and 1.21 ± 0.56 g/L, and the high-sensitivity C-reactive protein (hs-CRP) levels were 6.54 ± 1.56 and 8.77 ± 1.94 mg/L, respectively, with statistically significant differences (P < 0.05). The cumulative incidence of MACEs in the observation group was significantly lower than that in the control group (P < 0.05). The incidence of adverse reactions was 13.73% (7/51) in the observation group and 10.64% (5/47) in the control group, with no statistically significant difference (P > 0.05). Dapagliflozin combined with nocinto can improve myocardial microperfusion and left ventricular remodeling and reduce MACE incidence in patients with post-AMI heart failure and T2DM. The underlying mechanism may be related to the reduction in the expression levels of NT-proANP, GDF-15, and hs-CRP.

Evaluation of N-terminal pro-atrial natriuretic peptide and Soluble ST2 as Predictors for Cardiovascular Diseases in Patients with Type 2 Diabetes in Al-Basra, Iraq

Evaluation of N-terminal pro-atrial natriuretic peptide and Soluble ST2 as Predictors for Cardiovascular Diseases in Patients with Type 2 Diabetes in Al-Basra, Iraq

Low irisin levels predict acutely decompensated heart failure in type 2 diabetes mellitus patients

Abstract Funding Acknowledgements None. Background Acutely decompensated heart failure (ADHF) continues to be associated with unacceptably increasing in-hospital mortality rates and one-year mortality rates. Distinct scenarios of the natural course of ADHF relate to clinical heterogeneity among patients admitted to hospitals, cardiac dysfunction etiology, precipitating factors contributing to heart failure (HF) decompensation including type 2 diabetes mellitus (T2DM). The aim of this study was to determine the discriminative value of irisin for ADHF in T2DM patients with hemodynamically stable chronic HF. Methods A total of 738 patients with T2DM were prescreened using the local database of "Vita Center" (Ukraine). Using criteria of inclusion (male/female with age of ≥18 years, established T2DM with hemodynamically stable chronic HF, glycosylated hemoglobin &amp;lt; 6.9%, informed consent to participate in the study), we enrolled 489 patients with T2DM with concomitant chronic HF I-IV New York Heart Association (NYHA) functional classes. We enrolled 480 T2DM patients with any phenotype of HF and followed them for 52 weeks. Hemodynamic performances and the serum levels of biomarkers were detected at the study entry. The primary clinical end-point was ADHF that led to urgent hospitalization. Results We found that the serum levels of N-terminal natriuretic pro-peptide (NT-proBNP) were higher (1719 [980-2457] pmol/mL vs. 1057 [570-2607] pmol/mL, respectively) and the levels of irisin were lower (4.96 [3.14-6.85] ng/mL vs. 7.95 [5.73-9.16] ng/mL) in ADHF patients than in those without ADHF. The ROC curve analysis showed that the estimated cut-off point for serum irisin levels (ADHF versus non-ADHF) was 7.85 ng/mL (area under curve [AUC] = 0.869 (95% CI = 0.800-0.937), sensitivity = 82.7%, specificity = 73.5%; p = 0.0001). The multivariate logistic regression yielded that the serum levels of irisin &amp;lt; 7.85 ng/mL (OR = 1.20; p = 0.001) and NT-proBNP &amp;gt; 1215 pmol/mL (OR = 1.18; p = 0.001) retained the predictors for ADHF. Kaplan-Meier plots (Figure) showed a significant difference of clinical end-point accumulations in patients with HF depending on irisin levels (&amp;lt;7.85 ng/mL versus ≥7.85 ng/mL). The intra-class correlation coefficient for inter-observer reproducibility of LV dimensions was 0.88 (95% CI = 0.83–0.92), of LVEF was 0.93 (95% CI = 0.90–0.97), of LAVI was 0.92 (95% CI = 0.89–0.94), and of E/e’ was 0.90 (95% CI = 0.87–0.94). Along with it, the intra-class correlation coefficient for the intra-observer reproducibility of LV dimensions was 0.91 (95% CI = 0.88–0.95), of LVEF was 0.94 (95% CI = 0.90–0.98), of LAVI was 0.95 (95% CI = 0.93–0.97), and of E/e’ was 0.92 (95% CI = 0.90–0.95). In conclusion, we established that decreased levels of irisin were associated with ADHF presentation in chronic HF patients with T2DM independently from NT-proBNP.Flow chart of the study designThe Kaplan–Meier analysis of ADHF

Biomarkers for predicting atrial fibrillation: An explorative sub-analysis of the randomised SCREEN-AF trial

Background Atrial fibrillation (AF) is a common treatable risk factor for stroke. Screening for paroxysmal AF in general practice is difficult, but biomarkers might help improve screening strategies. Objectives We investigated six blood biomarkers for predicting paroxysmal AF in general practice. Methods This was a pre-specified sub-study of the SCREEN-AF RCT done in Germany. Between 12/2017-03/2019, we enrolled ambulatory individuals aged 75 years or older with a history of hypertension but without known AF. Participants in the intervention group received active AF screening with a wearable patch, continuous ECG monitoring for 2x2 weeks and usual care in the control group. The primary endpoint was ECG-confirmed AF within six months after randomisation. High-sensitive Troponin I (hsTnI), brain natriuretic peptide (BNP), N-terminal pro-B-type natriuretic peptide (NT-pro BNP), N-terminal pro atrial natriuretic peptide (NT-ANP), mid-regional pro atrial natriuretic peptide (MR-pro ANP) and C-reactive protein (CRP) plasma levels were investigated at randomisation for predicting AF within six months after randomisation. Results Blood samples were available for 291 of 301 (96.7%) participants, including 8 with AF (3%). Five biomarkers showed higher median results in AF-patients: BNP 78 vs. 41 ng/L (p = 0.012), NT-pro BNP 273 vs. 186 ng/L (p = 0.029), NT-proANP 4.4 vs. 3.5 nmol/L (p = 0.027), MR-pro ANP 164 vs. 125 pmol/L (p = 0.016) and hsTnI 7.4 vs. 3.9 ng/L (p = 0.012). CRP levels were not different between groups (2.8 vs 1.9 mg/L, p = 0.1706). Conclusion Natriuretic peptide levels and hsTnI are higher in patients with AF than without and may help select patients for AF screening, but larger trials are needed.

Post-cardiac arrest temporal evolution of left ventricular function in a rat model: speckle-tracking echocardiography and cardiac circulating biomarkers.

There is little information from experimental studies regarding the evolution of post-resuscitation cardiac arrest [post-return of spontaneous circulation (post-ROSC)] myocardial dysfunction during mid-term follow-up. For this purpose, we assessed left ventricular (LV) function and circulating cardiac biomarkers at different time points in a rat model of cardiac arrest (CA). Rats were divided into two groups: control and post-ROSC rats. Eight minutes of untreated ventricular fibrillation were followed by 8 min of cardiopulmonary resuscitation. Conventional and speckle-tracking echocardiographic (STE) parameters and cardiac circulating biomarkers concentrations were assessed, at 3, 4, 72, and 96 h post-ROSC. At 3 and 4 h post-ROSC, LV systolic function was severely impaired, and high-sensitivity cardiac troponin T and N-terminal pro-atrial natriuretic peptide (NT-proANP) plasma concentrations were significantly increased, compared with control rats (P < 0.0001 for all). At 72 and 96 h post-ROSC, LV ejection fraction (LVEF) normalized. At 96 h, the following variables were significantly different from control rats: early trans-mitral peak velocity, 56.8 ± 3.1 vs. 87.8 ± 3.8 cm/s, P < 0.0001; late trans-mitral peak velocity, 50.6 ± 4.7 vs. 73.7 ± 4.2 cm/s, P < 0.0001; mean s' wave velocity, 4.6 ± 0.3 vs. 5.9 ± 0.3 cm/s, P < 0.0001, global longitudinal strain (GLS) -7.5 ± 0.5 and vs. -11 ± 1.2%, P < 0.01; GLS rate (GLSR) -0.9 ± 0.4 and -2.3 ± 0.2 1/s, P < 0.01; and NT-proANP concentration, 2.5 (0.2; 6.0) vs. 0.4 (0.01; 1.0) nmol/L, P < 0.01. s' velocity, GLS, and GLSR indicated that LV systolic function was still impaired 96 h post-ROSC. These findings agree with NT-proANP concentrations, which continue to be high. Normalization of LVEF supports the use of STE for its greater sensitivity for monitoring post-CA cardiac function. Further investigations are needed to provide evidence of the post-ROSC LV diastolic function pattern.

N-terminal pro atrial natriuretic peptide as a prognostic marker of cardiac resynchronization therapy recipients

BackgroundAlthough the dynamic changes of atrial natriuretic peptide (ANP) expressions in a failing heart are well-documented, the clinical implications of detailed measurements of each ANP molecular form processed from proANP remain unclear. MethodsPatients screening was conducted on patients who were eligible for cardiac resynchronization therapy (CRT) between 2014 and 2019 in our institution. Blood samples and echocardiographic parameters were collected on the day before and six months after implantation. Total ANP, proANP, and N-terminal fragment of proANP (NT-proANP) were examined as predictive biomarkers for cardiac death, left ventricular assist device implantation, and heart failure hospitalization following CRT implantation. ResultsA total of 86 subjects (mean age 70 years, 64 males) who underwent successful CRT implantation were enrolled. Plasma levels of total ANP, proANP, and NT-proANP were not normally distributed [25.8 pM (interquartile range: 11.1–53.1), 2.2 pM (1.0–5.4), and 4.1 nM (2.4–7.1), respectively]. Over a median follow-up of 2.7 years, 31 patients (2 deaths and 29 heart failure hospitalizations) reached the endpoints. Among the different ANP forms, only NT-proANP emerged as an independent predictor of the composite outcome (adjusted odds ratio of 2.542 in those with levels above vs. below the median, 95 % confidence interval 1.151–5.615, p = 0.021). NT-proANP levels were associated with left atrial volume and left diastolic functional parameters and decreased in response to echocardiographic improvements at six months post-implantation (16 ± 44 % decrease in responders vs 18 ± 60 % increase in non-responders, p = 0.005). ConclusionPre-implantation NT-proANP levels could serve as a predictive factor for clinical outcomes in recipients of CRT.

Proteomic Correlates of the Urinary Protein/Creatinine Ratio in Heart Failure With Preserved Ejection Fraction

Proteinuria is common in heart failure with preserved ejection fraction (HFpEF), but its biologic correlates are poorly understood. We assessed the relation between 49 plasma proteins and the urinary protein/creatinine ratio (UPCR) in 365 participants in the Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist Trial. Linear regression and network analysis were used to represent relations between protein biomarkers and UPCR. Higher UPCR was associated with older age, a greater proportion of female gender, smaller prevalence of previous myocardial infarction, and greater prevalence of diabetes, insulin use, smoking, and statin use, in addition to a lower estimated glomerular filtration rate, hematocrit, and diastolic blood pressure. Growth differentiation factor 15 (GDF-15; β=0.15, p <0.0001), followed by N-terminal proatrial natriuretic peptide (NT-proANP; β=0.774, p <0.0001), adiponectin (β=0.0005, p <0.0001), fibroblast growth factor 23 (FGF-23, β=0.177; p <0.0001), and soluble tumor necrosis factor receptors I (β=0.002, p <0.0001) and II (β=0.093, p <0.0001) revealed the strongest associations with UPCR. Network analysis showed that UPCR is linked to various proteins primarily through FGF-23, which, along with GDF-15, indicated node characteristics with strong connectivity, whereas UPCR did not. In a model that included FGF-23 and UPCR, the former was predictive of the risk of death or heart-failure hospital admission (standardized hazard ratio 1.83, 95% confidence interval 1.49 to 2.26, p <0.0001) and/or all-cause death (standardized hazard ratio 1.59, 95% confidence interval 1.22 to 2.07, p=0.0005), whereas UPCR was not prognostic. Proteinuria in HFpEF exhibits distinct proteomic correlates, primarily through its association with FGF-23, a well-known prognostic marker in HFpEF. However, in contrast to FGF-23, UPCR does not hold independent prognostic value.

Enhancement of Bottle Gourd Oil Activity via Optimized Self-Dispersing Lipid Formulations (SDLFs) to Mitigate Isoproterenol-Evoked Cardiac Toxicity in Rats via Modulating BMP, MMP2, and miRNA-21 and miRNA-23a Genes' Expression.

Bottle gourd (BG) oil (family Cucurbitaceae) has several pharmacological activities including a reduction of the hazard of cardiovascular and atherosclerosis conditions. This work aimed to develop and optimize self-dispersing lipid formulations (SDLFs) of BG oil by applying a full 32 factorial design. The formulation variables (oil concentration and surfactant mixture ratio) showed an obvious impact on the characters of the prepared BG-SDLFs including droplet size (DS), polydispersity index (PDI), emulsification time (ET), and transmission percentage (Tr%). The optimum BG-SDLF composed of 30% oil and Tween 80/Cremophor® RH40 (1:1) showed good emulsification characteristics and a better drug release profile compared with BG oil. In vivo study in isoproterenol-injected rats showed that BG oil and the optimized BG-SDLF improved cardiac function, by elevating the miRNA-23a gene expression level and decreasing miRNA-21 gene expression. They also caused the inhibition of the plasma B-type natriuretic peptide (BNP), N-terminal proatrial natriuretic peptide (NT-pro-BNP), cystatin c, galectin-3, lipoprotein-associated phospholipase A2 (Lp-PLA2), matrix metallopeptidase 2 (MMP2), cardiac troponin I (cTnI), and cardiac troponin T (cTnT). Our study demonstrated that BG oil and the optimized BG-SDLF provided a cardioprotection against isoproterenol-induced cardiac toxicity with better results in groups treated with the optimized BG-SDLF.

Corin deficiency impairs cardiac function in mouse models of heart failure.

Corin is a protease in the natriuretic peptide system. Deleterious CORIN variants are associated with hypertension and heart disease. It remains unclear if and to what extent corin deficiency may contribute to heart failure (HF). Corin knockout (KO) mice were used as a model. Cardiac function was assessed by echocardiography and tissue analysis in Corin KO mice at different ages or subjected to transverse aortic constriction (TAC), which increased pressure overload. Heart and lung tissues were analyzed for cardiac hypertrophy and lung edema using wheat germ agglutinin, Sirius red, Masson's trichrome, and Prussian blue staining. Recombinant corin was tested for its effect on cardiac function in the TAC-operated Corin KO mice. Selected gene expression in the heart was examined by RT-PCR. ELISA was used to analyze factors in plasma. Corin KO mice had progressive cardiac dysfunction with cardiac hypertrophy and fibrosis after 9 months of age, likely due to chronic hypertension. When Corin KO mice were subjected to TAC at 10-12 weeks of age, cardiac function decreased more rapidly than in similarly treated wild-type mice. When the TAC-operated Corin KO mice were treated with recombinant corin protein, cardiac dysfunction, hypertrophy, and fibrosis were ameliorated. The corin treatment also decreased the gene expression associated with cardiac hypertrophy and fibrosis, increased plasma cGMP levels, lowered plasma levels of N-terminal pro-atrial natriuretic peptide, angiotensin II, and aldosterone, and lessened lung edema in the Corin KO mice subjected to TAC. Corin deficiency impairs cardiac function and exacerbates HF development in mice. Corin protein may be used to reduce cardiac hypertrophy and fibrosis, suppress the renin-angiotensin-aldosterone system, and improve cardiac function in HF.

The Diagnostic Accuracy of N-Terminal Pro-B-Type Natriuretic Peptide and Soluble ST2 for Heart Failure in Chronic Kidney Disease Patients: A Comparative Analysis.

BACKGROUND N-terminal proatrial natriuretic peptide (NT-proBNP) levels are often markedly elevated in patients with chronic kidney disease (CKD). Identifying novel biomarkers is an important step toward effective diagnosis. Interleukin-1 receptor-like 1 (IL1RL1) protein and human/Soluble suppression of tumorigenesis-2 (sST2) are promising biomarkers for heart failure (HF). This study aimed to assess the trend of NT-proBNP and sST2 in chronic kidney disease and their diagnostic value for HF. MATERIAL AND METHODS This study was carried out on 420 patients who were divided into a no heart failure group (N=182) and a heart failure group (N=238). Spearman correlation analysis was used to test the association of sST2 and NT-proBNP with renal function. The diagnostic value of each biomarker was assessed using receiver operating characteristic (ROC) curves according to 3 different forms: Total group (n=420), non-CKD group (n=217), and CKD group (n=203). RESULTS A striking correlation between eGFR and NT-proBNP (r=-0.525; P<0.001) seemed to be far stronger than that with sST2 (r=-0.147; P<0.05). The optimum cutoff points for sST2 and NT-proBNP to detect HF were 28.960 ng/mL and 1280 pg/mL, respectively, in total, 28.71 ng/mL and 481 pg/mL, respectively, in non-CKD patients, and 30.55 ng/mL and 3314 pg/mL, respectively, in CKD patients. The combined model of sST2 and NT-proBNP was superior to the model of sST2 or NT-proBNP alone, and the difference was statistically significant (P<0.05). CONCLUSIONS The diagnostic value of sST2 is less affected by decreased renal function. sST2 combined with NT-proBNP may improve the diagnostic accuracy of HF.

Characterization of the Cardiac Structure and Function of Conscious D2.B10-Dmdmdx/J (D2-mdx) mice from 16-17 to 24-25 Weeks of Age.

Duchenne muscular dystrophy (DMD) is the most common form of muscle degenerative hereditary disease. Muscular replacement by fibrosis and calcification are the principal causes of progressive and severe musculoskeletal, respiratory, and cardiac dysfunction. To date, the D2.B10-Dmdmdx/J (D2-mdx) model is proposed as the closest to DMD, but the results are controversial. In this study, the cardiac structure and function was characterized in D2-mdx mice from 16-17 up to 24-25 weeks of age. Echocardiographic assessment in conscious mice, gross pathology, and histological and cardiac biomarker analyses were performed. At 16-17 weeks of age, D2-mdx mice presented mild left ventricular function impairment and increased pulmonary vascular resistance. Cardiac fibrosis was more extended in the right ventricle, principally on the epicardium. In 24-25-week-old D2-mdx mice, functional and structural alterations increased but with large individual variation. High-sensitivity cardiac Troponin T, but not N-terminal pro-atrial natriuretic peptide, plasma levels were increased. In conclusion, left ventricle remodeling was mild to moderate in both young and adult mice. We confirmed that right ventricle epicardial fibrosis is the most outstanding finding in D2-mdx mice. Further long-term studies are needed to evaluate whether this mouse model can also be considered a model of DMD cardiomyopathy.

Association between glomerular filtration rate and plasma N-terminal pro-atrial natriuretic peptide concentration in dogs.

To investigate the association between plasma N-terminal pro-atrial natriuretic peptide concentration and glomerular filtration rate in dogs. Dogs were classified into four categories by bodyweight. Dogs were divided into four groups (Groups 1 to 4) based on glomerular filtration rate estimates using plasma iohexol clearance per bodyweight category. Generalised linear models were built to explore the relationship between plasma N-terminal pro-atrial natriuretic peptide concentration and glomerular filtration rate and the effect of confounders on plasma N-terminal pro-atrial natriuretic peptide concentration. Fifty-three dogs were included (Group 1, 25; Group 2, seven; Group 3, five; and Group 4, 16). The medians (interquartile range) N-terminal pro-atrial natriuretic peptide concentrations for Groups 1 to 4 were 7224 pg/mL (4766 to 10,254 mg/dL), 8958 pg/mL (4935 to 11,271 mg/dL), 9280 pg/mL (9195 to 10,384 mg/dL) and 12,683 pg/mL (9133 to 19,217 mg/dL), respectively. Group 4, estimated to have the highest reduction in glomerular filtration rate, had a higher plasma N-terminal pro-atrial natriuretic peptide concentration than Groups 1 to 3. Based on the final generalised linear model, influencing factors for plasma N-terminal pro-atrial natriuretic peptide concentration were plasma iohexol clearance (-0.136; 95% confidence interval, -0.227 to -0.046) and bodyweight (-0.058; 95% confidence interval, -0.098 to -0.018). N-terminal pro-atrial natriuretic peptide concentration is associated with the glomerular filtration rate.

Low Plasma Levels of Irisin Predict Acutely Decompensated Heart Failure in Type 2 Diabetes Mellitus Patients with Chronic Heart Failure.

The aim of this study was to determine the discriminative value of irisin for acutely decompensated heart failure (ADHF) in type 2 diabetes mellitus (T2DM) patients with chronic HF. We included 480 T2DM patients with any phenotype of HF and followed them for 52 weeks. Hemodynamic performances and the serum levels of biomarkers were detected at the study entry. The primary clinical end-point was ADHF that led to urgent hospitalization. We found that the serum levels of N-terminal natriuretic pro-peptide (NT-proBNP) were higher (1719 [980-2457] pmol/mL vs. 1057 [570-2607] pmol/mL, respectively) and the levels of irisin were lower (4.96 [3.14-6.85] ng/mL vs. 7.95 [5.73-9.16] ng/mL) in ADHF patients than in those without ADHF. The ROC curve analysis showed that the estimated cut-off point for serum irisin levels (ADHF versus non-ADHF) was 7.85 ng/mL (area under curve [AUC] = 0.869 (95% CI = 0.800-0.937), sensitivity = 82.7%, specificity = 73.5%; p = 0.0001). The multivariate logistic regression yielded that the serum levels of irisin < 7.85 ng/mL (OR = 1.20; p = 0.001) and NT-proBNP > 1215 pmol/mL (OR = 1.18; p = 0.001) retained the predictors for ADHF. Kaplan-Meier plots showed a significant difference of clinical end-point accumulations in patients with HF depending on irisin levels (<7.85 ng/mL versus ≥7.85 ng/mL). In conclusion, we established that decreased levels of irisin were associated with ADHF presentation in chronic HF patients with T2DM independently from NT-proBNP.

Associations of atrial natriuretic peptide with measures of insulin and adipose depots.

Low concentrations of natriuretic peptides (NPs) have been associated with greater risk for Type 2 diabetes (T2D). African American individuals (AA) have lower NP levels and are disproportionately burdened by T2D. The purpose of this study was to test the hypothesis that higher post-challenge insulin in AA adults is associated with lower plasma N-terminal pro-atrial natriuretic peptide (NT-proANP). A secondary purpose was to explore associations between NT-proANP and adipose depots. Participants were 112 AA and European American (EA) adult men and women. Measures of insulin were obtained from an oral glucose tolerance test and hyperinsulinemic-euglycemic glucose clamp. Total and regional adipose depots were measured from DXA and MRI. Multiple linear regression analysis was used to assess associations of NT-proANP with measures of insulin and adipose depots. Lower NT-proANP concentrations in AA participants was not independent of 30-min insulin area under the curve (AUC). NT-proANP was inversely associated with 30-min insulin AUC in AA participants, and with fasting insulin and HOMA-IR in EA participants. Thigh subcutaneous adipose tissue and perimuscular adipose tissue were positively associated with NT-proANP in EA participants. Higher post-challenge insulin may contribute to lower ANP concentrations in AA adults.

Plasma N-terminal pro-atrial natriuretic peptide concentrations are affected by dehydration in healthy dogs.

Plasma N-terminal pro-atrial natriuretic peptide (NT-proANP) and plasma N-terminal pro-B-type natriuretic peptide (NT-proBNP) concentrations may be affected by the hydration status. This study aimed to evaluate the effect of dehydration on plasma NT-proANP and NT-proBNP concentrations in healthy dogs. This prospective study included five clinically healthy dogs. Furosemide was administered intravenously at 2-4 mg/kg every 1-2 hours until completion of the dehydration model. The dehydration model was considered complete when weight loss was ≥5% and findings of dehydration on physical examination were observed. Plasma NT-proANP and NT-proBNP concentrations were compared at three-time points: before the dehydration model was created (point 1), at the completion of the dehydration model (point 2), and when dehydration was judged to have improved (point 3). Association between plasma NT-proANP and NT-proBNP concentrations, and each clinical variable (physical examination, blood pressure, blood chemistry, blood gases, and echocardiography) was assessed using linear regression analysis. Plasma NT-proANP concentration decreased significantly from point 2 to point 1 (p < 0.05), whereas plasma NT-proBNP concentration showed a decreasing trend but did not differ significantly between points 1 and 2. Plasma NT-proANP concentration correlated significantly with body weight (R2 = 0.178) and plasma NT-proBNP concentration (R2 = 0.284) (p < 0.05, respectively), and plasma NT-proBNP concentration correlated significantly with electrolytes (sodium, R2 = 0.439; potassium, R2 = 0.444; and chloride, R2 = 0.419), and echocardiographic parameters [diastolic left ventricular internal diameter (LVIDd) R2 = 0.519; weight-standardized LVIDd, R2 = 0.535] (p < 0.01, respectively). The plasma NT-proANP concentrations decreased with dehydration. However, the plasma NT-proBNP concentration did not change with mild dehydration and reflected left ventricular morphology.

Activin A directly impairs human cardiomyocyte contractile function indicating a potential role in heart failure development.

Activin A has been linked to cardiac dysfunction in aging and disease, with elevated circulating levels found in patients with hypertension, atherosclerosis, and heart failure. Here, we investigated whether Activin A directly impairs cardiomyocyte (CM) contractile function and kinetics utilizing cell, tissue, and animal models. Hydrodynamic gene delivery-mediated overexpression of Activin A in wild-type mice was sufficient to impair cardiac function, and resulted in increased cardiac stress markers (N-terminal pro-atrial natriuretic peptide) and cardiac atrophy. In human-induced pluripotent stem cell-derived (hiPSC) CMs, Activin A caused increased phosphorylation of SMAD2/3 and significantly upregulated SERPINE1 and FSTL3 (markers of SMAD2/3 activation and activin signaling, respectively). Activin A signaling in hiPSC-CMs resulted in impaired contractility, prolonged relaxation kinetics, and spontaneous beating in a dose-dependent manner. To identify the cardiac cellular source of Activin A, inflammatory cytokines were applied to human cardiac fibroblasts. Interleukin -1β induced a strong upregulation of Activin A. Mechanistically, we observed that Activin A-treated hiPSC-CMs exhibited impaired diastolic calcium handling with reduced expression of calcium regulatory genes (SERCA2, RYR2, CACNB2). Importantly, when Activin A was inhibited with an anti-Activin A antibody, maladaptive calcium handling and CM contractile dysfunction were abrogated. Therefore, inflammatory cytokines may play a key role by acting on cardiac fibroblasts, causing local upregulation of Activin A that directly acts on CMs to impair contractility. These findings demonstrate that Activin A acts directly on CMs, which may contribute to the cardiac dysfunction seen in aging populations and in patients with heart failure.

Effects of glucose and blood pressure reduction on subclinical cardiac damage: Results from ADVANCE

ObjectiveObservational data suggest a potential for subclinical cardiac damage from intensive blood glucose or blood pressure (BP) control, particularly in adults with very low blood glucose and BP levels. However, this has not been tested in a randomized trial. MethodsThe Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified Research Controlled Evaluation (ADVANCE) study was a factorial, randomized trial designed to test the effects of intensive blood glucose (hemoglobin A1c ≤6.5% versus usual care) and intensive BP (combination of perindopril-indapamide versus placebo) control on vascular events in adults with diabetes. Using mixed effects tobit models, we determined the effect of the randomized interventions on change in subclinical cardiac injury (high sensitivity cardiac troponin T [hs-cTnT]) and strain (N-terminal b-type pro natriuretic peptide [NT-proBNP]), 1 year after randomization. ResultsAmong the 682 participants, mean age was 66.1 (SD, 6.5) years; 40% were women. Mean baseline hemoglobin A1c was 7.4% (SD, 1.5) and systolic/diastolic BP was 147 (SD,21)/81 (SD,11) mmHg. After 1 year, intensive versus standard glucose control did not significantly change hs-cTnT (1.5%; 95%CI:-4.9,8.2) or NT-proBNP (−10.3%; 95%CI: −20.2%,0.9%). Intensive versus standard BP control also did not affect hs-cTnT (−2.9%; 95%CI: −8.9,3.6), but did significantly lower NT-proBNP by 21.6% (95%CI:-30.2%,-11.9%). Changes in systolic BP at 1 year (versus baseline) were strongly associated with NT-proBNP (P = 0.004), but not hs-cTnT (P = 0.95). ConclusionsIn adults with diabetes, intensive BP control reduced NT-proBNP without increasing hs-cTnT, supporting the benefits and safety of intensive BP control in adults with diabetes.This trial is registered at clinicaltrials.gov, number: NCT00145925.

Elevated N-terminal pro C-type natriuretic peptide is associated with mortality in patients undergoing transcatheter aortic valve replacement

BackgroundUnlike N-terminal pro-B-type natriuretic peptide (NT-proBNP), which have been extensively studied, little is known about the role of N-terminal pro-C-type natriuretic peptide (NT-proCNP) for predicting survival post transcatheter aortic valve replacement (TAVR).MethodsA total of 309 patients were included in the analysis. Patients were grouped into quartiles (Q1–4) according to the baseline NT-proCNP value. Blood for NT-proCNP analysis was obtained prior to TAVR procedure. The primary endpoint was mortality after a median follow-up of 32 months. Multivariable Cox proportional hazards regression models analyzed prognostic factors. The predictive capability was compared between NT-proBNP and NT-proCNP using receiver operator curve (ROC) analysis.ResultsA total of 309 subjects with the mean age of 76.8 ± 6.3 years, among whom 58.6% were male, were included in the analysis. A total of 58 (18.8%) patients died during follow-up. Cox multivariable analyses indicated society of thoracic surgeons (STS)-score was a strong independent predictor for mortality (hazard ratio (HR) 1.08, 95% confidential interval (CI) 1.05–1.12, P < 0.001). Elevated NT-proCNP was associated with a higher risk of cardiovascular mortality (HR 1.02, 95% CI 1.00–1.03, P = 0.025) and All-cause mortality (HR 1.01, 95% CI 1.00–1.03, P = 0.027), whereas NT-proBNP showed a small effect size on mortality. ROC analysis indicated that NT-proCNP was superior to NT-proBNP for TAVR risk evaluation in patients with left ventricular ejection fraction (LVEF) < 50% [(Area under the curve (AUC)-values of 0.79 (0.69; 0.87) vs. 0.59 (0.48; 0.69), P = 0.0453].ConclusionsNT-proCNP and STS-Score were the independent prognostic factors of mortality among TAVR patients. Furthermore, NT-proCNP was superior to NT-proBNP for TAVR risk evaluation in patients with LVEF < 50%.Trial registration NCT02803294, 16/06/2016.

Abstract P157: Racial Differences In Atrial Natriuretic Peptide And Insulin

Low circulating concentrations of the natriuretic peptides (NPs) have been associated with greater risk for Type 2 diabetes (T2D). As a group, African Americans (AA) have lower NP levels and are disproportionately burdened by T2D. Insulin, which is higher in AA, has been shown to regulate NP concentration by increasing the NP clearance receptor. This secondary analysis tests the hypothesis that higher insulin in AA will be associated with lower levels of plasma N-terminal pro-atrial natriuretic peptide (NT-proANP). Participants were 120 AA and European American (EA) men and women ages 19-45 years. Measures of insulin, including fasting insulin and insulin total and incremental area under the curve (AUC and iAUC, respectively, at 30 and 120 m), were derived from an oral glucose tolerance test (OGTT). Insulin sensitivity (SI Clamp ) was assessed using the euglycemic glucose clamp. NT-proANP was measured from fasting samples obtained during the OGTT. Differences in NT-proANP by race was evaluated with analysis of covariance while adjusting for age, sex, and BMI. Linear regression models were used to examine associations between NT-proANP and insulin measures while adjusting for age, sex, race, and BMI. Relative to EA, AA had higher insulin concentrations, lower insulin sensitivity, and lower NT-proANP levels (p&lt;0.05). Fasting insulin and 30 m insulin AUC were inversely associated with NT-proANP (p=0.02, p=0.02, and p=0.04, respectively). These results suggest that the lower NT-proANP observed in AA is related to higher insulin. Future research is needed to investigate the relationship between insulin, ANP, and the NP clearance receptor, particularly in populations at risk for chronic disease.