Serial Measurements Of NT-proBNP Research Articles

Effects of serial NT-proBNP measurements in patients with acute decompensated heart failure

Effects of serial NT-proBNP measurements in patients with acute decompensated heart failure

Abstract 18509: NT-proBNP Trajectories and Heart Failure Risk Associations in Middle to Older Ages in Adulthood: The Atherosclerosis Risk in Communities (ARIC) Study

Background: NT-proBNP is a powerful marker of heart failure (HF) risk. NT-proBNP levels increase with age; however, the impact of distinct longitudinal trajectories of NT-proBNP on future HF risk with aging is largely unexplored. Hypothesis: Middle-aged adults with higher baseline concentrations and steeper increases of NT-proBNP through older ages have greater HF risk. Methods: We performed a prospective analysis of 12,124 ARIC participants with 2 or more serial NT-proBNP measurements from Visits 2 through 6, without HF at baseline or HF events between the NT-proBNP assessments. We constructed linear mixed models to evaluate NT-proBNP trajectories for males and females. We defined 4 trajectories, using sex-specific medians to define high versus low: low baseline/low slope, low baseline/high slope, high baseline/low slope, high baseline/high slope. We used Kaplan Meier survival curves and multivariable Cox regression to evaluate the HF risk associations of different NT-proBNP trajectories. Results: The mean age was 57 years with 56% women and 23% Black adults, BMI 27. The median baseline NT-proBNP concentrations were 62 and 36 pg/mL and the average NT-proBNP slopes were 4.6% and 7.2% increase/year for women and men, respectively. Black individuals were more likely to have lower baseline levels, whereas those with diabetes, obesity, or prevalent coronary heart disease had higher slopes. Over a median 22-year follow-up, 2,772 HF events occurred. There was a stepwise increase in HF risk with higher baseline levels and slopes of NT-proBNP, with individuals with the high baseline/high slope NT-proBNP trajectory having a HR for HF of 3.70 (95% CI 3.26-4.20) compared to those with low baseline-low slope ( Figure ). Conclusions: Higher baseline concentrations and steeper increases of NT-proBNP with aging are associated with greater HF risk. Identifying and addressing modifiable determinants of NT-proBNP trajectories with aging may have implications for HF prevention.

Serial assessment of biomarkers and heart failure outcomes in patients with atrial fibrillation.

Cardiac functional and structural remodeling in patients with atrial fibrillation (AF) contributes to development of heart failure (HF) as their major cardiovascular comorbidity. Circulating biomarkers may reflect these cardiac alterations. ENGAGE AF-TIMI 48 was a randomized trial of edoxaban vs warfarin in 21,105 patients with AF. We performed a nested biomarker study in 8,765 patients, analyzing high-sensitivity troponin T (hsTnT), N-terminal B-type natriuretic peptide (NT-proBNP), and growth differentiation factor-15 (GDF-15) at baseline and 12 months. Of 8765 patients, 5207 had a history of HF, among whom 3996 had known ejection fraction (EF): 926 with reduced EF (HFrEF; ≤40%), 1043 with mildly-reduced EF (HFmrEF; 40-49%), and 2027 with preserved EF (HFpEF; ≥50%). Elevated baseline hsTnT, NT-proBNP, and GDF-15 were associated with higher risk of hospitalization for HF (HHF)/HF death overall and in subpopulations defined by HF history and EF (P<0.001 for each). These associations of outcome with each biomarker were consistent regardless of a history of HF or EF (P-interaction>0.05 for each). Patients who had an increase in or had persistently elevated values in any of the three biomarkers over 12 months were at higher risk for HHF/HF death in overall population (P<0.001 for each biomarker and category). Serial measurement of hsTnT, NT-proBNP, and GDF-15 revealed that higher baseline values, and increasing or persistently elevated values over 1 year are associated with higher risk of HF outcomes in patients with AF regardless of HF history or HF phenotype based on EF.

Association of Long-term Change in N-Terminal Pro–B-Type Natriuretic Peptide With Incident Heart Failure and Death

Most studies, especially in primary prevention patients, have evaluated N-terminal B-type natriuretic peptide (NT-proBNP) at one time point. Evaluation of change in NT-proBNP may improve risk stratification for incident cardiovascular events. To assess the association between change in NT-proBNP and risk for incident heart failure (HF) and death. Participants were recruited from 4 US communities enrolled in the Atherosclerosis Risk in Community (ARIC) study. Individuals who attended ARIC visits 2 and 4 (approximately 6 years apart) with measurements of NT-proBNP and without prevalent HF were included. Assays of NT-proBNP were conducted between 2011 and 2013, and analysis took place between July 2021 and October 2022. The primary exposure variable was NT-proBNP change between visits 2 and 4, modeled as change categories (<125 pg/mL or ≥125 pg/mL) and as percent change. The primary outcome measures were incident HF hospitalization and all-cause death. The association between changes in cardiovascular risk factors with change in NT-proBNP was further assessed. A total of 9776 individuals (mean [SD] age, 57.1 [5.7] years at visit 2; 5523 [56.5%] women) were included in the study. Compared with participants with NT-proBNP level less than 125 pg/mL at both visits, participants with NT-proBNP level of 125 pg/mL or higher at both visits had an increase in incident HF (adjusted hazard ratio [HR], 2.40 [95% CI, 2.00-2.88]) and mortality risk (HR, 1.68 [95% CI, 1.47-1.91). Participants with NT-proBNP levels of 125 pg/mL or higher at visit 2 and less than 125 pg/mL at visit 4 had similar risk for HF and death (HR, 1.01 [95% CI, 0.71-1.43]; HR, 0.79 [95% CI, 0.61-1.01]) compared with the group with NT-proBNP levels of less than 125 pg/mL at both visits. The percent change in NT-proBNP was positively associated with HF and death (HR, 1.06 [95% CI, 1.02-1.10]; HR, 1.05 [95% CI, 1.03-1.08] per 1-SD increase, respectively). Change in systolic blood pressure, low-density lipoprotein cholesterol, triglyceride level, body mass index, and estimated glomerular filtration rate were significantly associated with change in NT-proBNP. In this study, 6-year change in NT-proBNP reflected dynamic change in risk for HF events and death among community-dwelling adults without prevalent clinical HF. These results support the utility of serial NT-proBNP measurements to improve risk stratification of patients with pre-HF.

NT-proBNP and troponin I in high-grade aneurysmal subarachnoid hemorrhage: Relation to clinical course and outcome

PurposeTo investigate the association between two cardiac biomarkers, NT-proBNP and TnI, with intracranial pressure (ICP)−/cerebral perfusion pressure (CPP)-insults, cerebral pressure autoregulation, delayed ischemic neurological deficits (DIND), and clinical outcome after aneurysmal subarachnoid hemorrhage (aSAH). MethodsIn this retrospective study, 196 aSAH patients treated at the neurointensive care unit, Uppsala University Hospital, Sweden, 2011–2018, with ICP-monitoring and serial NT-proBNP and TnI measurements were included. The first 10 days were divided into early phase (day 1–3) and vasospasm phase (day 4–10). ResultsNT-proBNP and TnI were elevated above the reference interval at least once the first 10 days in 175 (89%) and 116 (59%) patients, respectively. In the vasospasm phase, higher NT-proBNP and TnI were associated with increased percentage of CPP below 60 mmHg. Higher TnI also correlated with more ICP-insults above 20 mmHg. NT-proBNP and TnI did not predict worse pressure autoregulation and DIND. Higher NT-proBNP and TnI were associated with mortality and unfavorable outcome in univariate, but not multivariate, analyses. ConclusionElevated NT-proBNP and TnI correlated with an increased burden of secondary ICP-/CPP-insults, but not with worse pressure autoregulation, DIND, and without independent association with clinical outcome.

Point of care with serial NT-proBNP measurement in patients with acute decompensated heart failure as a therapy-monitoring during hospitalization (POC–HF): Study protocol of a prospective, unblinded, randomized, controlled pilot trial

Despite important advances in diagnosis and medical therapy of heart failure (HF), disease monitoring and therapy guidance remains to be based on clinical signs and symptoms. NT-proBNP was repeatedly demonstrated to be a strong and independent predictor of morbidity and mortality in patients with HF. Only few – and conflicting – data are available on the efficacy of serial measurement of NT-proBNP as a tool for treatment monitoring in HF. These data are limited to the outpatient setting. Currently, no data are available on the effects of this approach in patients hospitalized for acute decompensated HF. The goal of this study is to explore whether the availability of serial NT-proBNP measurements may influence treatment decisions in patients with acute decompensated HF, and whether this leads to more rapid dose adjustments of prognostically beneficial medical therapies and earlier hospital discharge. In the intervention group, serial measurements of NT-proBNP every second business day are performed and made available to the treating physician, while no serial measurements are available in control group. HF therapy is left at the discretion of the treating physician. The primary endpoints are defined as the effects of monitoring NT-proBNP on medical HF therapy decisions, including type and dosing of medical therapies and the rapidity of adjustments, length of hospital stay, and evaluation of the changes in NT-proBNP values. Additional secondary endpoints include incidence of electrolyte imbalances and renal failure, changes in NYHA functional class, vital signs, body weight, quality of life, incidence of adverse events, transfer to Intensive Care Units, and mortality.

The minimal informative monitoring interval of N-terminal pro-B-type natriuretic peptide in patients with stable heart failure

BackgroundN-terminal pro-B-type natriuretic peptide (NT-proBNP) is a potential biomarker for monitoring the status of heart failure. However, the optimal monitoring interval of NT-proBNP is unknown. This study sought to investigate the minimal informative monitoring interval of NT-proBNP in patients with stable chronic heart failure.MethodsThis retrospective cohort study included patients who were admitted due to heart failure and subsequently followed with serial NT-proBNP measurements in a tertiary hospital. We analyzed NT-proBNP measured between six months after discharge and the earliest timepoint of: an alteration of medication regimen, readmission due to worsening of heart failure, or all-cause death. To distinguish progression of the disease from biological variability and measurement error, the signal-to-noise ratio method was applied with a random-effects model.ResultsIn the 368 patients included, NT-proBNP was measured for a median 6 times. In the random-effects model, signal (progression of disease) exceeded noise (biological variability and measurement error) at 7.9 months (95% confidence interval [CI]: 5.1–9.6), while noise corresponded to a 61% increase from baseline. In stratified analysis using the AHEAD risk score, the minimal informative monitoring interval shortened as the risk score increased (0–1 point: 12.2 months [95%CI: 10.3–14.4]; 2–3 points: 8.0 months [95%CI: 6.8–9.7]; 4–5 points: 3.3 months [95%CI: 3.0–3.8]).ConclusionsIn patients with stable chronic heart failure, the minimal informative monitoring interval of NT-proBNP measurement was 7.9 months in the current population, which varied with underlying risks. The optimal monitoring interval could be lengthened for patients at lower risks.

Urinary NT-proBNP as a potential noninvasive biomarker for screening of pulmonary hypertension in preterm infants: a pilot study.

This pilot study aimed to determine the feasibility of urinary NT-proBNP (NT-proBNP) as a potential noninvasive screening marker for pulmonary hypertension (PH). A prospective cross-sectional study was conducted. Preterm infants (PI) (birthweight <1500 gm and <30 weeks gestational age (GA)) were enrolled. Serial urinary NT-proBNP measurements and echocardiograms (ECHO) were performed at 28, 32, and 36 weeks. Thirty-six patients were included in the final analysis (BPD-PH group = 6, BPD group = 20, control = 10). Urinary NT-proBNP levels were higher in the BPD-PH group compared with BPD and control groups at all study intervals. A urine NT-proBNP cutoff level of 2345 pg/ml at 28 weeks of GA had a sensitivity and specificity of 83.3% and 84.2%, respectively, for detection of BPD-PH (AUC 0.816, p = 0.022). Urinary NT-proBNP measurement is feasible in preterm infants and appears to be a good noninvasive screening tool for PH.

Clinical Usefulness of N-terminal Prohormone of Brain Natriuretic Peptide and High Sensitivity Troponin T in Patients with Heart Failure Undergoing Cardiac Resynchronization Therapy.

Cardiac resynchronization therapy (CRT) is a valuable intracardiac device--based treatment option for a subgroup of patients with advanced heart failure (HF) and QRS prolongation. However, still a significant proportion of patients do not benefit from CRT implantation, labeled as non-responders. The aim of the present study was to evaluate the N-terminal prohormone of brain natriuretic peptide (NT-pro BNP) and high sensitivity troponin T (cTnThs) value as predictors of CRT response in a 12-month observation. The study included 46 patients with HF and implanted CRT-D. Levels of NT-pro BNP and cTnThs were assessed during a 12 month follow up. 46 consecutive patients (76% men) with a mean age of 64±8 were observed for 12 months. The CRT response criteria was met by 26 patients (56,5%). A significant decline in the NT-pro BNP concentrations was documented in responders (p=0.001). Moreover, ΔNT-pro BNP by at least 579 pg/ml had high sensitivity and specificity for identifying the CRT responders. There were no statistically significant differences in the results of cTnThs between the two study groups. The relative change in the level of NT-pro BNP by at least 43,5% allows to identify the responders to CRT after 12 months of follow-up. Serial measurements of NT-pro BNP can be a valuable tool for monitoring the effectiveness of CRT.

Dynamic risk stratification using serial measurements of plasma concentrations of natriuretic peptides in patients with heart failure

BackgroundPrognostic models for patients with chronic heart failure are generally based on a single assessment but treatment is often given with the intention of changing risk; re- evaluation of risk is an important aspect of care. The prognostic value of serial measurements of natriuretic peptides for the assessment of changes in risk is uncertain. AimsTo evaluate the prognostic value of serial measurements of plasma amino-terminal pro-brain natriuretic peptide (NT-proBNP) during follow-up of out-patients with chronic heart failure (CHF). MethodsPatients diagnosed with CHF between 2001 and 2014 at a single out-patient clinic serving a local community were included in this analysis. NT-proBNP was measured at the initial visit and serially during follow-up. Only patients who had one or more measurements of NT-proBNP after baseline, at 4, 12 and/or 24 months were included. ResultsAt baseline, amongst 1998 patients enrolled, the median age was 73 (IQR: 64–79) years, 70% were men, 31% were in NYHA class III/IV, and 77% had NT-proBNP >400 pg/mL. Median follow-up was 4.8 (IQR: 2.5–8.6) years. Serial measurements of NT-proBNP improved prediction of all-cause mortality at 3 years (c- statistic = 0.71) compared with using baseline data only (c-statistic = 0.67; p < 0.001) but a model using only the most recent NT-proBNP had an even higher c-statistic (0.72; p < 0.001). Similar results were obtained based on long-term prediction of mortality using all available follow-up data. ConclusionsSerial measurement of NT-proBNP in patients with CHF improves prediction of all-cause mortality. However, using the most recent value of NT-proBNP has similar predictive power as using serial measurements.

A Serial NT-proBNP Model to Improve Prognostication in Patients with Pulmonary Arterial Hypertension

Background: Baseline elevation in N-terminal pro-brain natriuretic peptide (NT-proBNP) in pulmonary arterial hypertension (PAH) patients is associated with worse outcomes. Serial measurement of commonly available biomarkers could improve the precision of prognostic estimates and our understanding of PAH pathophysiology. Methods: Included were 103 PAH patients with baseline elevated NT-proBNP prior to the initiation or escalation of therapy with at least two subsequent NT-proBNP measurements. Using patients’ serial measurements, a linear mixed-effects model extrapolated a baseline NT-proBNP (intercept) and evolution (slope). These model-determined values were then used in Cox proportional hazards analysis to determine predictors of survival. Time-dependent area under the curve (AUC) analysis compared survival discrimination of serial versus single measurements of NTproBNP. Results: Subjects were 50 ± 14 years; most had idiopathic PAH, congenital heart disease, or connective tissue disease. Survivors were younger than non-survivors 47 ± 14 versus 55 ± 12 years (p=0.002). A multivariable survival model using invasive and non-invasive covariates found NT-proBNP significantly predicted mortality. Timedependent AUC was significantly greater for modeled (intercept) versus measured NT-proBNP. Conclusions: Prognostic modeling utilizing serial NT-proBNP measurements better predict survival than a single baseline value. This evidence supports the conduct of future studies of serial measurement of NT-proBNP to further clarify its role in the clinical care of PAH patients.

Challenges of Using NT-Probnp for Response Assessment in Systemic AL Amyloidosis - Analysis of a Prospective Study

INTRODUCTIONTreatment outcomes in AL amyloidosis are dependent on the hematological response to chemotherapy translating into organ responses. Cardiac biomarker, N-terminal brain pro-natriuretic peptide (NT-proBNP), is the main determinant of cardiac response in AL amyloidosis. Strongly supported by the amyloidosis community, the FDA is considering use of NT-proBNP as the primary end point for clinical trials. A number of questions on the exact details on NT-proBNP in AL remain unanswered - rate of decrease over time, timing of NT-proBNP measurement (6 months or 12 months) and values to use as a baseline. We report the use of serial NT-proBNP measurements for cardiac response assessment at 6 months and 12 months addressing some of these questions.PATIENTS AND METHODSAll patients (n=650) recruited in the ALChemy study (a prospective observational study of all patients with AL amyloidosis undergoing chemotherapy) at the UK National Amyloidosis Centre from Sept 2009 to Jan 2014 with a minimum follow of 12 months and available NT-proBNP at 0, 6 and 12 months were included in this study. Organ involvement and hematologic/amyloidotic organ responses were assessed according to 2010 amyloidosis consensus criteria. The primary outcome measure was cardiac response as defined by NT-proBNP (Palladini et al JCO 2012). Correlation with 6 minute walk test was done where available.RESULTSA total of 343 patients were identified. The median age was 64 yrs. Organ involvement was: cardiac - 72%, renal - 73% and liver - 12% (median - 2 organs). The median creatinine was 90 _mol/L, median dFLC was 150 mg/L (range 10-15898 mg/L). The median NT-proBNP was 966 ng/L (range 33-30872 ng/L). The Mayo disease stage was: stage 1 - 26%, stage 2 - 47% and stage 3 Ð 27%. Serial six minute walk test results were available in 71 patients. Treatment was: thalidomide based regimes (mainly CTD) 56%, CyBorD Ð 30%, Melphalan-Dexamethasone - 5% and SCT 1%.A total of 204 patients had baseline NT-proBNP >650 ng/L (the threshold defined for NT-proBNP to be assessable for cardiac response) and were included in response analysis. Partial hematological response (or better) was seen in 92%, ³ VGPR in 66% and 22 (8%) were non-responders. The median decrease in dFLC was 85% over baseline at six months. The median NT-proBNP at baseline (for the response assessable group n=204) was 2669 ng/L. At six months, the median NT-proBNP had increased significantly to a median 3258ng/L (p<0.0001). At 12 months, there was a significant decrease in the NT-proBNP to a median of 2097 pMol/L (p=0.014). There was a discordance in NT-proBNP response at 6 and 12 months in 42 (44%) of patients (Figure 1). At six months, 52 (25%) patients had achieved NT-proBNP response and at 12 months 94 patients (46%) achieved an NT-proBNP response. When NT-proBNP at the 6 month time point was used as a baseline for response assessment, at 12 months, 106 (52%) patients met the criteria for a cardiac response. There was no significant difference in the median six minute walk test at baseline, 6 m and 12 months was 390m, 370m and 400 m. The six minute walk distance improved by greater than 10% over baseline at 6 and 12 months in 12% and 20% patients, worsened by more than 10% in 32% and 27% patients with change of less than 10% in the remainder.The median survival for this cohort has not been reached at 5 years with 60% survival at 7 years. Contrary to published data, NT-proBNP response at six months had a non-significant impact on survival whilst the NT-proBNP response at 12 months significantly impacted survival (median not reached for responders vs. 67 months for the non-responders; p<0.0001).CONCLUSIONSThis study shows the median NT-proBNP increased at six months over the baseline. There was a marked discrepancy in NT-proBNP at 6 months and 12 months Ð with a clear mis-classification of nearly half of all eventual cardiac responders. Consequently, the NTproBNP measurements at six months did not have a significant impact on survival whilst there was a marked impact at 12 months. NT-proBNP, as a primary end point, measure too early has potential for giving false negative results as a trial end point. This study highlights the critical importance of the timing of NT-proBNP measurements in response assessment for AL amyloidosis for clinical trials to avoid false negative results. [Display omitted] DisclosuresWechalekar:Janssen: Honoraria; Celgene: Honoraria; Glaxo Smith Kline: Honoraria; Takeda: Honoraria.

Should procalcitonin be measured routinely in acute decompensated heart failure?

To elucidate the prognostic role of procalcitonin (PCT) in patients with acute decompensated heart failure (ADHF) without clinical signs of infection at admission. Serial measurements of PCT and NT-proBNP were performed in 168 patients, aged 68 ± 10 years with ADHF followed by 3-month outcome evaluation. Cox regression analysis demonstrated significant predictive value of baseline PCT for all-cause death/hospitalization (area under the curve: 0.67; p = 0.013) at 90th day. The patients with persistently elevated PCT or with an increase during the first 72 h of hospitalization had the worst prognosis (p = 0.0002). Baseline and serial in-hospital measurements of PCT have significant prognostic properties for 3-month all-cause mortality/hospitalization in patients with ADHF without clinical signs of infection at admission.

(949) - The Potential Utility of Serial NT-proBNP Measurements in Determining a Therapeutic Response in Group I Pulmonary Artery Hypertension

(949) - The Potential Utility of Serial NT-proBNP Measurements in Determining a Therapeutic Response in Group I Pulmonary Artery Hypertension

Abstract 12455: Evaluation of N-Terminal Pro-B-type Natriuretic Peptide as a Therapeutic Response Biomarker in Group I Pulmonary Arterial Hypertension

Purpose: Goal directed management of left heart failure with an NT-proBNP target-based approach has some evidence of providing a survival benefit. To evaluate the potential utility of serial NT-proBNP measurements for goal-directed therapy in right heart failure we retrospectively assessed NT-proBNP as a predictor for survival in Group I pulmonary arterial hypertension (PAH) patients. Methods: We identified 103 Group I PAH patients from a pulmonary hypertension registry who had baseline elevated NT-proBNP prior to either the initiation or escalation of therapy and at least two serial NT-proBNP measurements. In a two-step process, we (1) estimated baseline NT-proBNP and slope (rate of change of NT-proBNP) with a linear mixed-effects model using all patient data and then (2) compared the power of serial versus single measurements in predicting survival with measured and model-derived values of baseline NT-proBNP with a Receiver Operative Characteristic (ROC) curve analysis . Survival was determined using the Kaplan-Meier methodology. Results: ROC curve analysis revealed significantly higher AUC for model-derived NT-proBNP values compared to the measured values (AUC: for baseline 0.74 vs 0.66, p= 0.009; for slope 0.78 vs 0.66, p= 0.02). Optimal cutpoints for prediction of survival on baseline NT-proBNP were 2012 (measured) vs. 1810 (model-derived) pg/mL. The optimal cutpoint for model-derived change in NT-proBNP was -0.004 log10pg/mL/month. Sensitivity, specificity, and negative predictive values for the three predictor variables were: 64%, 67%, 80% (measured baseline NT-proBNP), 61%, 80%, 81% (model-derived baseline NT-proBNP) and 73%, 57%, 85% (model-derived slope). Conclusions: In PAH patients, serial NT-proBNP measurements better predict survival than single measurements. This retrospective finding reveals that changes in NT-proBNP are associated with overall survival in PAH patients, and set initial target values for a pilot prospective study of NT-proBNP goal-directed therapy.

Serial measurements of the Nt-ProBNP during the dry state in patients with systolic heart failure are predictors of the long-term prognosis

Objective: To evaluate the long-term predictive value of serial Nt-ProBNP during dry-state in patients with systolic heart failure (SHF).Methods: Nt-ProBNP was measured quarterly during a 6-month dry-state period in 40 SHF outpatients. Events: all-cause mortality or hospitalization. Follow-up: 5 years.Results: The Nt-ProBNP >1000 pg/ml (baseline and 6 months) and the variation rate (VR) >30% were independently associated with the survival and composite endpoint curve. VR >30% added significant prognostic information to the single Nt-ProBNP 1000 pg/ml cut-off. Patients with at least one Nt-ProBNP determination >1000 pg/ml were at greater risk of death.Conclusion: Serial Nt-ProBNP measurements in patients with SHF during the dry-state are strong predictors of the long-term prognosis.

Clinical impact of paravalvular leaks on biomarkers and survival after transcatheter aortic valve implantation

There is accumulating evidence that up to 20% of the implanted devices after TAVI are associated with a significant degree of paravalvular leaks, which appear to be associated with a negative clinical outcome. A total of 355 patients with severe aortic valvular stenosis (AVS) were treated by TAVI (Corevalve n = 222, Edwards Sapien n = 133). Survival, NT-proBNP and the grade of PVL were quantified up to 12 months after implantation. Technical success rate was 97.8%. Thirty-day mortality was 9.6%. Post-procedural transvalvular aortic regurgitation was seen only in a minority of cases (5%), whereas PVL were frequently observed (grade: <1+ in 58.2%, ≥1-<2 in 33.9%, and ≥2 in 7.9%). There was a clear relation-ship between PVL and adverse outcome (P < 0.001). After a transient increase, NT-proBNP showed a significant decline. Interestingly, a PVL ≥2+ was associated with a much higher rise in NT-proBNP compared to the other groups (P < 0.01), and a post-procedural increase in NT-proBNP by more than 1640 ng L(-1) within 5 days was associated with a significant increase in rate of death (P < 0.01). TAVI is an efficient treatment option for high-risk patients with severe AVS. The incidence of PVL is an inacceptable clinical problem. Serial measurement of NT-proBNP can be used for risk-stratification in patients with a significant PVL. In general, PVL graded ≥2+ is associated with a dramatically increased 6-month mortality. Therefore, any action to reduce paraprosthetical regurgitation is highly recommended.

Adding serial N‐terminal pro brain natriuretic peptide measurements to optimal clinical management in outpatients with systolic heart failure: a multicentre randomized clinical trial (NorthStar monitoring study)

This study was designed to evaluate a new NT-proBNP monitoring concept in outpatients with systolic heart failure (HF). This was a multicentre, prospective randomized open-label blinded endpoint study. A total of 407 systolic HF patients were allocated to either clinical management (n = 208) or clinical management + NT-proBNP monitoring (n = 199) and followed for 2.5 years. If NT-proBNP increased >30%, a clinical checklist was completed and treatment initiated. The patients were matched at randomization and were 73 years old, 25% were females, 85% were NYHA class I-II, LVEF was 30%, and NT-proBNP 1955 pg/mL. NT-proBNP monitoring did not improve outcome, the hazard ratio for the primary composite endpoint (death or a cardiovascular admission) being 0.96 [95% confidence interval (CI) 0.71-1.29, P = 0.766]. NT-proBNP monitoring did not induce a significant change in the pharmacological strategy (P > 0.05 for all comparisons). In patients in whom NT-proBNP increased >30% (25% of the patients) during follow-up, a higher frequency of admission (69% vs. 47%, P = 0.002), a higher number of admission days (14 vs. 5 days, P = 0.003) and number of admissions (2 vs. 1, P = 0.009), and a lower quality of life (P = 0.032) and a poorer functional class (37% vs. 18% in NYHA class III-IV, P < 0.001) were observed. Adding serial measurements of NT-proBNP to optimal clinical management was not associated with a change in pharmacological strategy and did not improve outcome. However, survivors in whom NT-proBNP increased >30% showed a poorer functional class, clinical outcome, and quality of life. www.centerwatch: 173491 (NorthStar).

Interleukin-6 is the strongest predictor of 30-day mortality in patients with cardiogenic shock due to myocardial infarction

IntroductionCardiogenic shock (CS) remains the leading cause of death in patients hospitalized for myocardial infarction (MI). Systemic inflammation with inappropriate vasodilatation is observed in many patients with CS and may contribute to an excess mortality rate. The purpose of this study was to determine the predictive role of serial measurements of Nt-proBNP, interleukin-6 (IL-6), and procalcitonin (PCT) for 30-day mortality in patients with CS due to MI.MethodsThe present study is a prospective single-center study including 87 patients with MI complicated by CS treated with acute revascularization and intraaortic balloon counterpulsation (IABP) support. Predictive values of plasma levels at admission (T0), after 24 hours (T1), and after 72 hours (T2) were examined according to 30-day mortality.ResultsSignificant differences between survivors (n = 59) and nonsurvivors (n = 28) were seen for Nt-proBNP at T0, for IL-6 at T0 and T1, and for PCT at T1 and T2. According to ROC analyses, the highest accuracy predicting 30-day mortality was seen at T0 for IL-6, at T1 for PCT, and at T2 for PCT. In univariate analysis, significant values were found for Nt-proBNP at T1, and for IL-6 and PCT at all points in time. Within the multivariate analysis, age, creatinine, and IL-6 were significant determinants of 30-day mortality, in which IL-6 showed the highest level of significance.ConclusionsIn patients with MI complicated by CS, IL-6 represented a reliable independent early prognostic marker of 30-day mortality. PCT revealed a significant value at later points in time, whereas Nt-proBNP seemed to be of lower relevance.

Reference Limits for N-Terminal-pro-B-Type Natriuretic Peptide in Healthy Individuals (from the Framingham Heart Study)

N-terminal pro-B-type natriuretic peptide (NT-pro-BNP) is a commonly measured cardiovascular biomarker in ambulatory and hospital settings. Nonetheless, there are limited data regarding "normal" ranges for NT-pro-BNP in healthy subjects, despite the importance of such information for interpreting natriuretic peptide measurements. In this study, a healthy reference sample free of cardiovascular disease from the Framingham Heart Study Generation 3 cohort was examined; there were 2,285 subjects (mean age 38 years, 56% women). Plasma NT-pro-BNP levels were measured using the Roche Diagnostics Elecsys 2010 assay, and reference values (2.5th, 50th, and 97.5th quantiles) were determined using empiric and quantile regression methods. Gender, age, blood pressure, and body mass index accounted for approximately 33% of the interindividual variability in NT-pro-BNP in the reference sample. NT-pro-BNP values were substantially higher in women compared to men at every age, and levels increased with increasing age for both genders. Using quantile regression, the upper reference values (97.5th quantile) for NT-pro-BNP were 42.5 to 106.4 pg/ml in men (depending on age) and 111.0 to 215.9 pg/ml in women. Intraindividual variability was assessed in an additional 12 healthy subjects, who had serial NT-pro-BNP measurements over 1 month. Intraclass correlation was 0.85, indicating that most of the variability in NT-pro-BNP concentrations was among rather than within subjects. However, the reference change value was 100%, suggesting that small proportional differences in NT-pro-BNP could be attributable to analytic variability. In conclusion, the reference limits obtained from this large, healthy, community-based sample may aid in the evaluation of NT-pro-BNP concentrations measured for clinical and research purposes.