N-terminal Prohormone Brain Natriuretic Peptide Levels Research Articles

Effects of 1-year tofacitinib therapy on angiogenic biomarkers in rheumatoid arthritis.

Cardiovascular (CV) morbidity and mortality, and perpetuated synovial angiogenesis have been associated with RA. In our study we evaluated angiogenic factors in relation to vascular inflammation and function, and clinical markers in RA patients undergoing 1-year tofacitinib therapy. Thirty RA patients treated with either 5 mg or 10 mg twice daily tofacitinib were included in a 12-month follow-up study. Eventually, 26 patients completed the study and were included in data analysis. Levels of various angiogenic cytokines (TNF-α, IL-6), growth factors [VEGF, basic fibroblast (bFGF), epidermal (EGF), placental (PlGF)], cathepsin K (CathK), CXC chemokine ligand 8 (CXCL8), galectin-3 (Gal-3) and N-terminal prohormone brain natriuretic peptide (NT-proBNP) were determined at baseline, and at 6 and 12 months after initiating tofacitinib treatment. In order to assess flow-mediated vasodilation, common carotid intima-media thickness (ccIMT) and carotid-femoral pulse-wave velocity, ultrasonography was performed. Synovial and aortic inflammation was also assessed by 18F-fluorodeoxyglucose-PET/CT. One-year tofacitinib therapy significantly decreased IL-6, VEGF, bFGF, EGF, PlGF and CathK, while it increased Gal-3 production (P < 0.05). bFGF, PlGF and NT-proBNP levels were higher, while platelet-endothelial cell adhesion molecule 1 (PECAM-1) levels were lower in RF-seropositive patients (P < 0.05). TNF-α, bFGF and PlGF correlated with post-treatment synovial inflammation, while aortic inflammation was rather dependent on IL-6 and PECAM-1 as determined by PET/CT (P < 0.05). In the correlation analyses, NT-proBNP, CXCL8 and Cath variables correlated with ccIMT (P < 0.05). Decreasing production of bFGF, PlGF or IL-6 by 1-year tofacitinib therapy potentially inhibits synovial and aortic inflammation. Although NT-proBNP, CXCL8 and CathK were associated with ccIMT, their role in RA-associated atherosclerosis needs to be further evaluated.

Influence of growth and metabolic markers on hs-troponin T and NT-proBNP levels in healthy children.

As part of the LIFE Child study, we previously described the associations between N-terminal-pro-hormone brain natriuretic peptide (NT-proBNP) and hs-troponin T (hs-TnT) levels and an individual's sex, age and pubertal status, as well as with body mass index (BMI) and serum lipid levels. For NT-proBNP, we found inverse associations with advancing puberty, increasing BMI and serum lipid levels. These findings led us to further question the putative influences of the developing individual's metabolic and growth status as represented by levels of insulin-like growth factor-1 (IGF-1) and IGF-1-binding protein-3 (IGF-BP3) as well as hemoglobin A1c (HbA1c) and Cystatin C (CysC). Serum values, medical history and anthropometric data provided by 2522 children aged 0.25-18 years were collected and analyzed as per study protocol. A strong negative association between NT-proBNP values and IGF-1, IGF-BP3 and HbA1c levels was identified. For IGF-BP3, this interaction was modulated by sex and age, for HbA1c only by age. For hs-TnT, a positive association was found with IGF-BP3, IGF-1 and CysC. The association between hs-TnT and IGF-1 was sex dependent. The association between CysC and hs-TnT was stronger in girls, but the interaction with age was only seen in boys. Between hs-TnT and HbA1c, the association was significantly negative and modulated by age. Based on our large pediatric cohort, we could identify age- and sex-dependent interactions between the metabolic status represented by IGF-1, IGF-BP3, CysC and HbA1c levels and the cardiac markers NT-proBNP and hs-TnT.

Tolerability and beneficial effects of sacubitril/valsartan on systemic right ventricular failure

ObjectivePatients with a systemic right ventricle (sRV) in the context of transposition of the great arteries (TGA) after atrial switch or congenitally corrected TGA (ccTGA) are prone to sRV dysfunction....

Association between N-Terminal Prohormone Brain Natriuretic Peptide and Decreased Skeletal Muscle Mass in a Healthy Adult Population: A Cross-Sectional Study.

Although an inverse association between the N-terminal prohormone brain natriuretic peptide (NT-proBNP) and obesity exists, only few major studies have assessed the association between NT-proBNP levels and skeletal muscle mass in asymptomatic healthy adults. Therefore, this cross-sectional study was conducted. We assessed participants who underwent health examinations at Kangbuk Samsung Hospital in South Korea from January 2012 to December 2019. Appendicular skeletal muscle mass was measured using a bioelectrical impedance analyzer, and the skeletal muscle mass index (SMI) was calculated. Participants were divided into the control, mildly low skeletal muscle mass (LMM) (-2 standard deviation [SD] < SMI ≤-1 [SD]), and severely LMM groups (SD ≤-2) based on their SMI. The association between elevated NT-proBNP level (≥125 pg/mL) and skeletal muscle mass was assessed using multivariable logistic regression analysis with adjustment for confounding factors. This study enrolled 15,013 participants (mean age, 37.52±9.52; men, 54.24%; control, n=12,827; mildly LMM, n=1,998; severely LMM, n=188). Prevalence of elevated NT-proBNP was higher in mildly and severely LMM groups than in the control group (control, 1.19%; mildly LMM, 1.4%; severely LMM, 4.26%; P=0.001). The adjusted odds ratio (OR) of elevated NT-proBNP was significantly higher in severely LMM (OR, 2.87; 95% confidence interval [CI], 1.3 to 6.37) than in control (OR, 1.00; reference) or mildly LMM groups (OR, 1.24; 95% CI, 0.81 to 1.89). Our results showed that NT-proBNP elevation were more prevalent in participants with LMM. In addition, our study showed an association between skeletal muscle mass and NT-proBNP level in a relatively young and healthy adult population.

AKUT OLMAYAN DİSPNEDE N-TERMİNAL PROHORMON BEYİN NATRİÜRETİK PEPTİT SEVİYESİ İLE EKOKARDİYOGRAFİK SOL VENTRİKÜL SİSTOLİK VEYA DİYASTOLİK İŞLEV BOZUKLUĞU İLİŞKİSİ

Objective: The aim of the study was to evaluate serum N-terminal prohormone brain natriuretic peptide (NT-proBNP) level and evidence of left ventricular (LV) systolic dysfunction (SD) or diastolic dysfunction (DD) in non-obese patients with non-acute dyspnea. &#x0D; Methods: This study retrospectively evaluated the serum NT-proBNP level and LV SD or DD from transthoracic echocardiography (TTE) in patients with non-acute dyspnea between October 2020 and October 2021. The normal limit for the serum NT-proBNP level (125 pg/ml) was used as the cut-off value. &#x0D; Results: Ultimately, 435 patients were included in the study. In 61% of the patients (n=264), the NT-proBNP level was elevated (≥ 125 pg/ml). There was no evidence of SD or DD in 56% of the patients (n=147) with ≥ 125 pg/ml. The patients whose NT-proBNP ≥ 125 but who had no SD or DD had a significantly higher H2FPEF score ≥ 6, atrial fibrillation, malignancy, previous COVID-19, and need for hospitalization than the patients whose NT-proBNP &lt; 125 and who had no SD or DD (13% vs. 4%; 5% vs. 1%; 16% vs. 9%; 29% vs. 5%; and 25% vs. 11%, respectively). An NT-proBNP value &lt; 752.1 pg/ml excluded SD with 72.5% sensitivity and 83.1% specificity and &lt; 350.3 pg/ml excluded DD with 71.3% sensitivity and 75.5% specificity. &#x0D; Conclusion: A high NT-proBNP value does not always indicate SD or DD. NT-proBNP measurement may detect not only overt heart failure but also subclinical LV dysfunction in various clinical entities, in addition to adding prognostic significance in non-acute dyspnea.

Pulmonary hypertension screening in children with sickle cell disease.

Screening for pulmonary hypertension (PHT) is recommended in children with sickle cell disease (SCD). However, best approaches are poorly described. We examined the utility of PHT symptoms, echocardiogram (ECHO), N-terminal-pro hormone brain natriuretic peptide (NT-proBNP), and BNP to screen for PHT in the SCD pediatric population. Children (8-18years old) with SCD-HbSS and HbSthal° were prospectively included and underwent PHT screening. The screening consisted of a comprehensive PHT symptoms evaluation, ECHO measurement, and NT-proBNP and BNP levels. A total of 73 patients were included (mean age 12±5.7years; >80% on hydroxyurea), of which 37% had a symptom consistent with PHT, including exertional dyspnea (26.5%), fatigue (17.6%), palpitation (14.7%), and chest pain (10.3%). ECHO was obtained in 53 (72.6%) patients, with only ECHO of 48 patients included in the final analysis. Elevated ECHO peak tricuspid regurgitant jet velocity (TRV) >2.5m/s or indirect findings to suggest PHT were seen in only two of 48 (4.2%). No significant differences were seen between those with and without PHT symptoms when compared for NT-proBNP, BNP, hemoglobin, pulmonary function testing, fractional exhaled nitric oxide, asthma, oxygen saturation, and sleep apnea. PHT symptoms are not consistent with ECHO, NT-proBNP nor BNP findings in children with SCD. PHT prevalence based on TRV was low in children on hydroxyurea, therefore screening may not be warranted for this group.

The Prognostic Value of Natriuretic Peptides in Stable Patients with Suspected Acute Myocarditis: A Retrospective Study.

Risk stratification in acute myocarditis is based on the clinical signs of heart failure, the degree of cardiac dysfunction, and the findings in cardiac magnetic resonance (CMR). The aim of the current study is to examine the prognostic yield of the natriuretic peptide N-terminal-pro hormone Brain Natriuretic Peptide (NT-proBNP) and C-reactive protein (CRP) in acute myocarditis among patients with preserved/mildly reduced left ventricular ejection fraction (LVEF). We retrospectively analyzed 59 patients (median age 28 years, 76% males) with ICD-9 discharge diagnosis of acute myocarditis. Basic characteristics, echocardiographic, and laboratory parameters were obtained from computerized files. The median length of stay was 3, (IQR 2–5) days, and the median LVEF was 48% (IQR, 54–62%). High levels of NT-proBNP and CRP were associated with increased length of stay (r = 0.57, p < 0.001; r = 0.4 p = 0.001, respectively), while troponin level was not (r = 0.068, p = 0.61). During the index hospitalization, complications occurred in 14 (23.7%) patients. High NT-proBNP and CRP levels were associated with complications (p < 0.001, and p = 0.001, respectively), while troponin level was not (p = 0.452). In conclusion, routine measurement of NT-proBNP and CRP are preferred over troponin for risk stratification in hemodynamically stable myocarditis.

Effects of early myocardial reperfusion and perfusion on myocardial necrosis/dysfunction and inflammation in patients with ST-segment and non-ST-segment elevation acute coronary syndrome: results from the PLATelet inhibition and patients Outcomes (PLATO) trial.

AimsRestoration of myocardial blood flow and perfusion during percutaneous coronary intervention (PCI) measured using Thrombolysis in Myocardial Infarction (TIMI) flow grade (TFG) and perfusion grade (TMPG) is associated with improved outcomes in acute coronary syndrome (ACS). Associations between TFG/TMPG and changes in biomarkers reflecting myocardial damage/dysfunction and inflammation is unknown.Methods and resultsAmong 2606 patients included, TFG was evaluated in 2198 and TMPG in 1874 with ST-segment elevation myocardial infarction (STEMI) or non-ST-segment ACS (NSTE-ACS). Biomarkers reflecting myocardial necrosis [troponin T (TnT)], myocardial dysfunction [N-terminal prohormone brain natriuretic peptide (NT-proBNP)], inflammation [interleukin-6 (IL-6) and C-reactive protein (CRP)], and oxidative stress/ageing/inflammation [growth differentiation factor-15 (GDF-15)] were measured at baseline, discharge, and 1- and 6-month post-randomization. Associations between TFG/TMPG and changes in biomarker levels were evaluated using the Mann–Whitney–Wilcoxon signed test. In total, 1423 (54.6%) patients had STEMI and 1183 (45.4%) NSTE-ACS. Complete reperfusion after PCI with TFG = 3 was achieved in 1110 (85.3%) with STEMI and in 793 (88.5%) with NSTE-ACS. Normal myocardial perfusion with TMPG = 3 was achieved in 475 (41.6%) with STEMI and in 396 (54.0%) with NSTE-ACS. Levels of TnT, NT-proBNP, IL-6, CRP, and GDF-15 were substantially lower at discharge in patients with complete vs. incomplete TFG and STEMI (P < 0.01). This pattern was not observed for patients with NSTE-ACS. Patients with normal vs. abnormal TMPG and NSTE-ACS had lower levels of NT-proBNP at discharge (P = 0.01).ConclusionsSuccessful restoration of epicardial blood flow in STEMI was associated with less myocardial necrosis/dysfunction and inflammation. Attainment of normal myocardial perfusion was associated with less myocardial dysfunction in NSTE-ACS.

Is the N-terminal pro-B-type natriuretic peptide a predictor of cardiovascular events in hemodialysis patients?

Aim To evaluate the role of N-terminal pro-hormone brain natriuretic peptide (NT-proBNP) as a predictor of cardiovascular events (CVE) in patients receiving programmed hemodialysis (PHD).Material and methods This study included 74 patients (men, 64.8 %) older than 18 years receiving PHD. Data were processed using mean values of standard biochemical indexes for 16 months. NT-proBNP level was measured and transthoracic echocardiography (EchoCG) and bioimpedancemetry were performed at the time of inclusion into the study. Cumulative incidence of CVE for 16 months was evaluated in patients with different levels of NT-proBNP (quartile 1: &lt;1127 pg/ml; quartile 1-4: 1127-3210 pg/ml; quartile 4: &gt;3210 pg/ml) using the Kaplan-Meier method. For assessment of NT-proBNP as a CVE predictor, receiver operational characteristic curves (ROC curves) were constructed.Results The serum concentration of NT-proBNP was 2114.5 [1127; 3210.4] pg/ml. During 16 months, CVE were observed in 25.6 % of patients. The risk of CVE increased with increasing NT-proBNP quartile in the analysis of Kaplan-Meier curves (Log-Rank test, p=0.032). In this process, CVE did not develop in patients with NT-proBNP concentrations lower than 1127 pg/ml. The ROC analysis demonstrated a good predictive value of NT-proBNP (p=0.006, AUC 0.71, 95 % CI: 0.59-0.83). The optimum cut-off threshold of the NT-proBNP level predictive of CVE was 2093 pg/ml (sensitivity, 84.2 %, specificity, 58.2 %). CVE developed in patients with greater values of volumetric myocardial parameters, indirect signs of hyperhydration (higher predialysis sodium level and pulmonary artery systolic pressure), smaller volumes of substituate per dialysis procedure, and left ventricular systolic dysfunction (p&lt;0.05).Conclusion In patients receiving programmed extracorporeal therapy, the serum concentration of NT-proBNP was considerably higher than mean values in the general population. Apparently, serum NT-proBNP concentrations in the range of 1127-2093 pg/ml can be used as a predictor for a high risk of CVE in the dialysis population. Pronounced structural alterations of the myocardium, left ventricular systolic dysfunction, and hyperhydration are the factors that provide development of CVE on PHD. Large volumes of the PHD substitution solution are associated with a lower incidence of CVE in the dialysis population.

Can Circulating Cardiac Biomarkers Be Helpful in the Assessment of LMNA Mutation Carriers?

Mutations in the lamin A/C gene are variably phenotypically expressed; however, it is unclear whether circulating cardiac biomarkers are helpful in the detection and risk assessment of cardiolaminopathies. We sought to assess (1) clinical characteristics including serum biomarkers: high sensitivity troponin T (hsTnT) and N-terminal prohormone brain natriuretic peptide (NT-proBNP) in clinically stable cardiolaminopathy patients, and (2) outcome among pathogenic/likely pathogenic lamin A/C gene (LMNA) mutation carriers. Our single-centre cohort included 53 patients from 21 families. Clinical, laboratory, follow-up data were analysed. Median follow-up was 1522 days. The earliest abnormality, emerging in the second and third decades of life, was elevated hsTnT (in 12% and in 27% of patients, respectively), followed by the presence of atrioventricular block, heart failure, and malignant ventricular arrhythmia (MVA). In patients with missense vs. other mutations, we found no difference in MVA occurrence and, surprisingly, worse transplant-free survival. Increased levels of both hsTnT and NT-proBNP were strongly associated with MVA occurrence (HR > 13, p ≤ 0.02 in both) in univariable analysis. In multivariable analysis, NT-proBNP level > 150 pg/mL was the only independent indicator of MVA. We conclude that assessment of circulating cardiac biomarkers may help in the detection and risk assessment of cardiolaminopathies.

Elevations in High-Sensitive Cardiac Troponin T and N-Terminal Prohormone Brain Natriuretic Peptide Levels in the Serum Can Predict the Development of Anthracycline-Induced Cardiomyopathy.

Anthracyclines remain the cornerstone of the treatment in many cancers including lymphomas, leukemia and sarcomas, and breast cancer. The cardiomyopathy that develops from anthracyclines can lead to heart failure and decreased survival. Multiple mechanisms are involved in the pathophysiology of anthracycline-induced heart failure. We hypothesize that anthracycline-induced cardiac (AIC) pathology can be monitored using a panel of blood biomarkers including high-sensitive cardiac troponin T (hs-cTnT) for myocyte necrosis and N-terminal prohormone brain natriuretic peptide (NT-proBNP) for parietal stress. A prospective, institutionally approved study recruited all patients with cancer scheduled to start anthracycline chemotherapy in the Transylvania University cancer clinics. Transthoracic 2D echocardiography and the measurements of NT-proBNP and hs-cTnT plasma levels were performed at the beginning of the study and 3 months and 6 months after anthracycline treatment initiation. The plasma levels of hs-cTnT at 3 months (rho = 0.439, P = 0.0001) and 6 months (rho = 0.490, P = 0.0001) are correlated with AIC occurrence. For a cutoff value of hs-cTnT at 3 months > 0.008 ng/mL, we obtained 66.7% sensitivity and 67.9% specificity for developing AIC at 6 months, with a 54.5% positive predictive value and a 87.8% negative predictive value. The NT-proBNP serum levels at 3 months (rho = 0.495, P = 0.0001) and 6 months (rho = 0.638, P = 0.0001) are correlated with an AIC diagnosis at 6 months. For a cutoff value of NT-proBNP at 3 months >118.5 pg/mL, we obtained 80% sensitivity and 79.2% specificity for evolution to AIC at 6 months, with 52.2% positive predictive value and 93.3% negative predictive value. In anthracycline-treated cancer patients, the increase in plasma levels of NT-proBNP and of hs-cTnT can predict the development of anthracycline-induced cardiomyopathy. Early identification of at-risk patients will potentially allow for targeted dose reductions and will diminish the number of patients developing cardiac pathology.

Value of natriuretic peptides and tissue Doppler imaging in the estimation of left ventricular filling pressure in patients with cardiac amyloidosis

BackgroundEstimation of left ventricular filling pressures (LVFP) is a determining factor in the follow-up of patients with cardiac amyloidosis (CA). Natriuretic peptides (NPs) and tissue Doppler imaging may be used...

Relation of N-Terminal Pro–B-Type Natriuretic Peptide and Left Ventricular Diastolic Function to Exercise Tolerance in Patients With Significant Valvular Heart Disease and Normal Left Ventricular Systolic Function

An association between N-terminal prohormone brain natriuretic peptide (NT-proBNP) and exercise tolerance in patients with valvular heart disease (VHD) has been suggested; however, there are few data available regarding this relation. The aim of this study is to evaluate the correlation between exercise tolerance and NT-proBNP in patients with asymptomatic or mildly symptomatic significant VHD and normal left ventricular ejection fraction (LV EF). A total of 96 patients with asymptomatic or mildly symptomatic VHD and normal LV EF (≥50%) underwent cardiopulmonary exercise echocardiography. NT-proBNP levels were determined at baseline and after exercise in 3hours. Patients were divided in 2 groups based on lower (<26ml/kg/min, n= 47) or higher (≥26ml/kg/min, n=49) peak oxygen consumption (VO2) as a representation of exercise tolerance. In the 2 groups, after adjusting for age and gender, the NT-proBNP level after exercise in 3hours, left atrial volume index before exercise, right ventricular systolic pressure before exercise, E velocity after exercise, and E/e' ratio after exercise varied significantly. In addition, peak VO2 was inversely related to NT-proBNP before (r=-0.352, p <0.001) and after exercise (r=-0.351, p <0.001). The NT-proBNP level before exercise was directly related to the left atrial volume index, E/e' ratio, and right ventricular systolic pressure before and after exercise. NT-proBNP after exercise was also directly related to the same parameters. NT-proBNP levels both before and after exercise were higher in the group with lower exercise tolerance. In conclusion, through the correlation among exercise tolerance, NT-proBNP, and parameters of diastolic dysfunction, we demonstrated that diastolic dysfunction and NT-proBNP could predict exercise tolerance in patients with significant VHD and normal LV EF.

Troponin I and echocardiography in patients with systemic sclerosis and matched population controls

Objectives: Cardiac manifestations in systemic sclerosis (SSc) are associated with poor prognosis. Few studies have investigated cardiac troponins in SSc. We studied the relationships between echocardiographic abnormalities, cardiac biomarkers, and disease manifestations in a population-based cohort of patients with SSc and controls.Method: The study comprised 110 patients with SSc and 105 age- and sex-matched population-based controls. We examined ventricular function, heart valves, and estimated pulmonary arterial pressure (ePAP) by echocardiography in all participants. Disease characteristics, manifest ischaemic heart disease (IHD), and measurements of N-terminal prohormone brain natriuretic peptide (NT-proBNP) and high-sensitivity cardiac troponin I (hs-cTnI) were tabulated.Results: NT-proBNP and hs-cTnI levels were higher in SSc patients than controls. Both NT-proBNP and hs-cTnI were associated with the presence of echocardiographic abnormalities. Forty-four SSc patients and 23 control subjects had abnormal echocardiograms (p = 0.002). As a group, SSc patients had lower (but normal) left ventricular ejection fraction (LVEF, p = 0.02), more regional hypokinesia (p = 0.02), and more valve regurgitations (p = 0.01) than controls. Thirteen patients and four controls had manifest IHD. Decreased right ventricular (RV) function (n = 7) and elevated ePAP (n = 15) were exclusively detected among SSc patients.Conclusions: Both NTproBNP and hs-cTnI were associated with echocardiographic abnormalities, which were more prevalent in SSc patients than in controls. Our results thus suggest that hs-cTnI could be a potential cardiac biomarker in SSc. Low RV function and signs of pulmonary hypertension (PH) were uniquely found in the SSc group. SSc patients had more valve regurgitation than controls, an observation that warrants more clinical attention.

Bortezomib-Containing Regimens for the Treatment of Newly Diagnosed and Relapsed Amyloid Light Chain Amyloidosis: A Single-Center Experience.

The proteasome is an exciting target for the development of novel anticancer therapies. Recent evidence has suggested that bortezomib, a dipeptide boronate proteasome inhibitor, exhibits unprecedented single-agent activity in amyloid light chain (AL) amyloidosis. We performed a retrospective review of the use of bortezomib-containing regimens to assess the rapidity and quality of response at our institution. A total of 52 patients with documented newly diagnosed and relapsed AL amyloidosis treated with bortezomib-containing regimens were identified from our institutional database. After a median of 4 cycles (range, 1-22 cycles), a hematologic response was seen in 49 patients (94.2%), including a complete response in 15 (28.8%), a very good partial response in 25 (48.1%), and a partial response in 9 (17.3%). At 6 weeks, 37 patients had already achieved a partial response. An organ response at 6 months was documented in 31 patients (59.6%). With respect to the cardiac response, a > 30% decrease in N-terminal pro-hormone brain natriuretic peptide (NT-proBNP) was observed in 17 of 35 evaluable patients (48.6%; NT-proBNP > 650 ng/L) at a median of 6 months. Overall survival was shorter for the patients with NT-proBNP > 5000 ng/L and for those who achieved less than a very good partial response. Bortezomib is a safe and well-tolerated therapy for patients with AL amyloidosis with a rapid hematologic response and cardiac response, as assessed by the NT-proBNP level.

Natriuretic Peptide and High-Sensitivity Troponin for Cardiovascular Risk Prediction in Diabetes: The Atherosclerosis Risk in Communities (ARIC) Study.

OBJECTIVECardiovascular disease (CVD) is the major cause of morbidity and mortality in diabetes; yet, heterogeneity in CVD risk has been suggested in diabetes, providing a compelling rationale for improving diabetes risk stratification. We hypothesized that N-terminal prohormone brain natriuretic peptide (NTproBNP) and high-sensitivity troponin T may enhance CVD risk stratification beyond commonly used markers of risk and that CVD risk is heterogeneous in diabetes.RESEARCH DESIGN AND METHODSAmong 8,402 participants without prevalent CVD at visit 4 (1996–1998) of the Atherosclerosis Risk in Communities (ARIC) study there were 1,510 subjects with diabetes (mean age 63 years, 52% women, 31% African American, and 60% hypertensive).RESULTSOver a median follow-up of 13.1 years, there were 540 incident fatal/nonfatal CVD events (coronary heart disease, heart failure, and stroke). Both troponin T ≥14 ng/L (hazard ratio [HR] 1.96 [95% CI 1.57–2.46]) and NTproBNP >125 pg/mL (1.61 [1.29–1.99]) were independent predictors of incident CVD events at multivariable Cox proportional hazard models. Addition of circulating cardiac biomarkers to traditional risk factors, abnormal electrocardiogram (ECG), and conventional markers of diabetes complications including retinopathy, nephropathy, and peripheral arterial disease significantly improved CVD risk prediction (net reclassification index 0.16 [95% CI 0.07–0.22]). Compared with individuals without diabetes, subjects with diabetes had 1.6-fold higher adjusted risk of incident CVD. However, participants with diabetes with normal cardiac biomarkers and no conventional complications/abnormal ECG (n = 725 [48%]) were at low risk (HR 1.12 [95% CI 0.95–1.31]), while those with abnormal cardiac biomarkers, alone (n = 186 [12%]) or in combination with conventional complications/abnormal ECG (n = 243 [16%]), were at greater risk (1.99 [1.59–2.50] and 2.80 [2.34–3.35], respectively).CONCLUSIONSAbnormal levels of NTproBNP and troponin T may help to distinguish individuals with high diabetes risk from those with low diabetes risk, providing incremental risk prediction beyond commonly used markers of risk.

Biological significance of miR-126 expression in atrial fibrillation and heart failure.

We investigated the biological significance of microRNA-126 (miR-126) expression in patients with atrial fibrillation (AF) and/or heart failure (HF) to examine the possible mechanism of miR-126-dependent AF and development of HF. A total of 103 patients were divided into three groups: AF group (18 men and 17 women, mean age: 65.62±12.72 years), HF group (17 men and 15 women, mean age: 63.95±19.71 years), and HF-AF group (20 men and 16 women, mean age: 66.56±14.37 years). Quantitative real-time PCR was used to measure relative miR-126 expression as calculated by the 2−ΔΔCt method. miR-126 was frequently downregulated in the 3 patient groups compared with controls. This reduction was significantly lower in permanent and persistent AF patients than in those with paroxysmal AF (P<0.05, t-test). Moreover, miR-126 expression was markedly lower in the HF-AF group compared with the AF and HF groups. The 3 patient groups had higher N-terminal prohormone brain natriuretic peptide (NT-proBNP) levels, lower left ventricular ejection fraction (LVEF), larger left atrial diameter, and higher cardiothoracic ratio compared with controls. There were significant differences in NT-proBNP levels and LVEF among the AF, HF, and HF-AF groups. Pearson correlation analysis showed that relative miR-126 expression was positively associated with LVEF, logarithm of NT-proBNP, left atrial diameter, cardiothoracic ratio, and age in HF-AF patients. Multiple linear regression analysis showed that miR-126 expression was positively correlated with LVEF, but negatively correlated with the logarithm of NT-pro BNP and the cardiothoracic ratio (all P<0.05). Serum miR-126 levels could serve as a potential candidate biomarker for evaluating the severity of AF and HF. However, to confirm these results, future studies with a larger and diverse patient population are necessary.

Assessment of right ventricular adaptability to loading conditions can improve the timing of listing to transplantation in patients with pulmonary arterial hypertension

Right ventricle (RV) performance is load dependent, and right-sided heart failure (RHF) is the main cause of death in pulmonary arterial hypertension (PAH). Prediction of RV worsening for timely identification of patients needing transplantation (Tx) is paramount. Assessment of RV adaptability to load has proved useful in certain clinical circumstances. This study assessed its predictive value for RHF-free and Tx-free outcome with PAH. Between 2006 and 2012, all potential Tx candidates with PAH, without RHF at the first evaluation, were selected for follow-up (except congenital heart diseases). At selection and at each follow-up, N-terminal prohormone brain natriuretic peptide (NT-proBNP) and the 6-minute walk distance were measured, and RV adaptability to load was assessed by echocardiography. Collected data were tested for the ability to predict RV stability and Tx-free survival. During a 12-month to 92-month follow-up, RHF developed in 23 of 79 evaluated patients, despite similar medication and no differences in initial RV size and ejection fraction compared with the patients who remained stable. However, unstable patients had an initially lower RV load-adaptation index and afterload-corrected peak global systolic longitudinal strain-rate values as well as higher RV dyssynchrony, tricuspid regurgitation, and NT-proBNP levels (p ≤ 0.01). At certain cutoff values, these variables appeared predictive for 1-year and 3-year freedom from RHF and 3-year Tx-free survival. An RV load-adaptation index reduction of ≥20% showed the highest predictive value (90.0%) for short-term (≤1 year) RV decompensation. Assessment of RV adaptability to load allows prediction of RV function and Tx-free survival with severe PAH during the next 1 to 3 years. This can improve the timing of listing for Tx.

5-year serial follow-up of clinical condition and ventricular function in patients after repair of tetralogy of Fallot

ObjectiveTo study the changes over time in biventricular size and function, and clinical parameters in patients after repair of tetralogy of Fallot (TOF) without subsequent pulmonary valve replacement (PVR). MethodsWe prospectively included 78 non-PVR patients (age 20(6–60)years at baseline), who were studied twice with a 5-year interval. Patients underwent magnetic resonance imaging for assessment of biventricular size and function. Exercise testing and electrocardiography were performed to determine peak oxygen uptake (peak VO2) and QRS duration. N-terminal prohormone brain natriuretic peptide (NT-proBNP) was assessed additionally. ResultsPulmonary regurgitation (PR), right ventricular (RV) volumes and QRS duration increased during 5-year follow-up (RV end-diastolic volume (EDV) 130±30ml/m2 to 138±34ml/m2; QRS 132±27msec to 139±27msec); peak VO2 decreased (96±19% to 91±17%). RV ejection fraction, RV effective stroke volume (eff.SV), and NT-proBNP levels remained unchanged. The slope of RVEDV increase was 1.6±3.0ml/m2/year, and depended on RVeff.SV, not on RVEDV, at baseline. Increase in RVEDV correlated with increase in QRS duration over time (r=0.28, p=0.016), and with decrease in RV mass/EDV ratio over time (r=−0.42, p<0.001), not with decrease in peak VO2. In subgroup analysis, patients with larger RVs at baseline showed larger increase in PR during follow-up and larger decrease in NYHA class over time. ConclusionsIn TOF patients with moderate RV dilatation, RVEDV increased by 1.6±3.0ml/m2/year, irrespective of RV size at baseline, but depended on RVeff.SV at baseline. Despite limited progression in RV size, unfavourable changes occurred during 5years follow-up, which suggests there is a need for close follow-up.

Clinical Implications of Serial Serum N-Terminal Prohormone Brain Natriuretic Peptide Levels in the Prediction of Outcome in Children With Dilated Cardiomyopathy

N-terminal prohormone brain natriuretic peptide (NT-proBNP) is known to be valuable as a prognostic marker for the management of heart failure. This study aimed to assess the serial changes of serum NT-proBNP levels as a prognostic factor for outcomes of pediatric dilated cardiomyopathy (DC). A retrospective study reviewed echocardiographic measurements and serum NT-proBNP levels obtained at the time of diagnosis, 3 and 6 months after diagnosis, and at the last follow-up in 68 children with DC. They were classified into 3 groups according to the last follow-up of the left ventricular (LV) function: group I (n = 37) with LV fractional shortening (FS) ≥25%, group II (n = 15) with 10% ≤ LVFS < 25%, and group III (n = 16) with LVFS <10% or cardiac death. The median age at diagnosis was 30 months and median duration of follow-up was 45 months (range 8 to 108 months). The origin of DC varied. Serial serum NT-proBNP levels showed statistically significant differences among the 3 groups. Although initial levels of serum NT-proBNP at diagnosis were not different from each other, group III maintained a higher NT-proBNP level throughout the duration of the follow-up. On multivariate Cox analysis, only the NT-proBNP level at 3 months was a significant predictor of an adverse outcome (hazard ratio 2.012, p = 0.028). The percent changes of NT-proBNP from diagnosis were not significant. Patients with DC with a serum NT-proBNP level ≥681 pg/ml at 3 months after diagnosis showed an increased risk of severe LV dysfunction or cardiac death (p <0.001, area under the curve = 0.846). In conclusion, the level of NT-proBNP in serum at 3 months after diagnosis could predict an adverse outcome in pediatric DC and could be used as a guide for long-term treatment plans.