Log-transformed N-terminal Pro-brain Natriuretic Peptide Research Articles

PS-C28-2: STROKE RISK OF THE ELDERLY PATIENTS WITH NOCTURNAL HYPERTENSION DEFINED USING HOME BLOOD PRESSURE MONITORING IN JAPANESE GENERAL PRACTICE POPULATION

Objective: To investigate the association between nocturnal hypertension defined using home blood pressure (BP) monitoring (HBPM) and the prevalence, extent of cardiovascular target organ damage (TOD), and cardiovascular disease (CVD) event risks in participants with ≧ 65 years in general clinical practice. Design and method: We used the dataset of the Japan Morning Surge-Home BP (J-HOP) Study that recruited 4,310 participants with cardiovascular risk factors. Among them, we assessed the participants with ≧ 65 years who measured nocturnal home BP (n = 1,349, mean age 72.0 year, 48.6% men). We define nocturnal hypertension as nocturnal systolic (SBP) ≧ 120 mmHg or diastolic (DBP) ≧ 70 mmHg, using HBPM. Nocturnal home BP was automatically measured at least 1 day within the 14 days (2 AM, 3 AM, and 4 AM). We use the average of all nocturnal home BP values. N-terminal pro-brain natriuretic peptide (NT-proBNP) and urine albumin: creatinine ratio (UACR) were used as surrogate markers of TOD. The CVD outcomes were incident stroke and coronary heart disease (CHD) events. Results: The prevalence of nocturnal hypertension defined by HBPM was 61.7% of all study participants with ≧ 65 years. The participants with nocturnal hypertension defined by HBPM presented higher levels of log-transformed NT-proBNP and UACR at baseline compared to those with controlled nocturnal BP group. Over a median 4.0-year follow-up (5,453 person-years), 36 stroke events and 31 CHD events occurred, respectively. The nocturnal hypertension group had a higher incidence rate of stroke events compared with the controlled BP group. Concerning CHD, the incidence rate of CHD was similar between two groups (Figure). Cox model results suggested that the participants with nocturnal hypertension had a higher risk of stroke compared to those with controlled nocturnal BP group after adjustments for log-transformed NT-proBNP and UACR levels (adjusted hazard ratio 3.42; 95% confidence interval 1.15–10.19). Conclusions: In this Japanese population with ≧ 65 years, the participants with nocturnal hypertension defined by HBPM was significantly associated with stroke risk, independently of the extent of TOD.

Abstract 14907: Association Between Adverse Pregnancy Outcomes and N-Terminal Pro-Brain Natriuretic Peptide 2-7 Years After Delivery: Numom2b Heart Health Study

Introduction: Adverse pregnancy outcomes (APOs), including gestational diabetes (GDM), hypertensive disorders of pregnancy (HDP), preterm birth (PTB), and small-for-gestational age (SGA), have been associated with increased risk of heart failure (HF), but mechanisms are poorly understood. We sought to examine the association between a history of APO and N-terminal pro-brain natriuretic peptide (NT-proBNP), a HF biomarker, after delivery. Methods: We included individuals from the NuMoM2b Heart Health Study who were recruited during their first pregnancy and followed longitudinally. We excluded individuals who had pre-pregnancy hypertension or diabetes. APOs were centrally adjudicated based on medical records. NT-proBNP was assessed at follow-up visit after delivery. We examined the association between a history of APO and elevated NT-proBNP (≥125 pg/mL) with logistic regression. We log-transformed NT-proBNP and also examined the association between history of APO and NT-proBNP with linear regression. Models were adjusted for demographic and cardiovascular risk factors at the time of NT-proBNP. Results: Of 4172 individuals, mean (SD) age was 30.7(5.6) years at 3 years follow-up after delivery and 170 (4%) had a history of GDM, 597 (14%) HDP, 321 (8%) had PTB, and 170 (4%) had SGA. Among the study population, 256 (6%) had elevated NT-proBNP. Individuals with GDM had a lower risk of elevated NT-proBNP levels (adjusted odds ratio 0.59 [95% confidence interval 0.38, 0.92]); while a history of HDP, PTB, or SGA was not associated with elevated NT-proBNP ( TABLE ). When NT-proBNP was examined as a continuous variable, a history of GDM (-0.20 [-0.35, -0.06] pg/mL) or HDP (-0.09 [-0.15, -0.02]) was associated with lower log-transformed NT-proBNP levels in adjusted models. Conclusions: In this cohort study, APOs were not associated with elevations in NT-proBNP, but GDM and HDP were paradoxically associated with lower NT-proBNP levels at 3 years post-delivery.

Myocardial Activity at 18F-FAPI PET/CT and Risk for Sudden Cardiac Death in Hypertrophic Cardiomyopathy.

Background Myocardial fibrosis contributes to adverse cardiovascular events in hypertrophic cardiomyopathy (HCM). Purpose To explore the characteristics of cardiac fibroblast activation protein inhibitor (FAPI) PET/CT imaging and its relationship with the risk of sudden cardiac death (SCD) in HCM. Materials and Methods In this prospective study from July 2021 to January 2022, participants with HCM and healthy control participants underwent cardiac fluorine 18 (18F)-labeled FAPI PET/CT imaging. Myocardial FAPI activity was quantified as intensity (target-to-background uptake ratio), extent (the percent of FAPI-avid myocardium of the left ventricle [LV]), and amount (the percent of FAPI-avid myocardium of LV × target-to-background ratio). Regional wall thickness was analyzed at cardiac MRI. The 5-year SCD risk score was calculated from the 2014 European Society of Cardiology guidelines. Univariable and multivariable linear regression analyses were used to identify factors related to the FAPI amount. The correlation between FAPI amount and 5-year SCD risk was explored. Results Fifty study participants with HCM (mean age, 43 years ± 13 [SD]; 32 men) and 22 healthy control participants (mean age, 45 years ± 17; 14 men) were included. All participants with HCM had intense and inhomogeneous cardiac FAPI activity in the LV myocardium that was higher than that in healthy control participants (median target-to-background ratio, 8.8 vs 2.1, respectively; P < .001). In HCM, more segments with FAPI activity were detected than the number of hypertrophic segments (median, 14 vs five, respectively; P < .001); 84% of nonhypertrophic segments showed FAPI activity. Log-transformed FAPI amount had a positive relationship with log-transformed N-terminal probrain natriuretic peptide, high-sensitive troponin I, and left atrial diameter and a negative relationship with LV ejection fraction z-score. Degree of FAPI activity positively correlated with the 5-year SCD risk score (r = 0.32; P = .03). Conclusion Fibroblast activation protein inhibitor (FAPI) PET/CT imaging indicated intense and heterogeneous activity in hypertrophic cardiomyopathy, and FAPI uptake was associated with 5-year risk of sudden cardiac death. © RSNA, 2022 Online supplemental material is available for this article.

Real-time image-guided lead placement in cardiac resynchronisation therapy: feasibility and outcome in a multicentre setting

Abstract Funding Acknowledgements Type of funding sources: None. Introduction Image-guidance to assist left ventricular (LV) lead placement may improve outcome after cardiac resynchronisation therapy (CRT). Because previous approaches and results varied greatly, the optimal strategy remains unknown. To date, only a few studies investigated ‘real-time’ guidance, and feasibility in a multicentre setting is lacking altogether. Methods In 30 patients from three hospitals, cardiac magnetic resonance imaging (MRI) was performed to identify myocardial scar and late mechanical activation (LMA). LMA was determined using radial strain, plotted over time. Segments without scar but clear LMA were classified as optimal, according to an accurate 36-segment model. LV-lead deployment was guided, in real-time, using live image-overlay with fluoroscopy. After 6 months, volumetric response was defined as ≥15% reduction in LV end-systolic volume (∆LVESV). Reduction in log-transformed N-terminal pro-brain natriuretic peptide (NT-proBNP) was assessed at 2 months. Results Real-time image-guidance was successful performed in all CRT patients (age 66±10 years; 59% male, 72% non-ischemic cardiomyopathy; 69% left bundle branch block). LV-leads were deployed as follows: within (24%), adjacent (52%), or remote (24%) from the pre-defined target. According to the traditional 18-segment model, a remote position occurred only once. On average, 86% of patients demonstrated a volumetric response (mean ∆LVESV 36±29%). In addition, lead placement was association with reduction in log-transformed NT-proBNP (Figure 1). Conclusion Real-time image-guidance towards a pre-defined target for LV-lead placement was feasible in a multicentre setting, and has promising clinical results. Efficacy will be further investigated in the randomised controlled ‘Advanced Image Supported Lead Placement in Cardiac Resynchronization Therapy’ trial.

Nighttime home blood pressure as a mediator of N-terminal pro-brain natriuretic peptide in cardiovascular events.

We tested our hypothesis that the association between N-terminal pro-brain natriuretic peptide (NT-proBNP) and cardiovascular disease (CVD) events is mediated in part by a pathway of increased nighttime blood pressure (BP) that involves volume overload. We used the data from the Japan Morning Surge-Home Blood Pressure (J-HOP) Nocturnal BP Study, which targeted 2476 Japanese participants who had a history of or risk for CVD (mean age 63.8 ± 10.2 years), along with their measured nighttime BP values assessed by a home BP device (measured at 2:00, 3:00 and 4:00 a.m.) and NT-proBNP levels. At baseline, elevated daytime (average of morning and evening) and nighttime home systolic BP (SBP) were independently associated with log-transformed NT-proBNP levels after adjustment for cardiovascular risk factors. During a median follow-up of 7.2 years, 150 participants experienced a CVD event (62 stroke events and 88 coronary artery disease events). After adjustment for cardiovascular risk factors and nighttime SBP, increased log-transformed NT-proBNP levels were independently associated with CVD events (hazard ratio [HR] per 1 unit, 1.67; 95% confidence interval [CI]: 1.16-2.40). Elevated nighttime home SBP was also independently associated with CVD events after adjustment for cardiovascular risk and log-transformed NT-proBNP (HR per standard deviation, 1.22; 95% CI: 1.001-1.50). The percentage of the association between NT-proBNP and CVD events mediated by nighttime home SBP was 15%. Our findings indicate a physiological pathway in which increased nighttime SBP contributes to the impact of elevated NT-proBNP levels on the incidence of CVD.

Reduction of estimated fluid volumes following initiation of empagliflozin in patients with type 2 diabetes and cardiovascular disease: a secondary analysis of the placebo-controlled, randomized EMBLEM trial

Backgrounds/AimSodium glucose co-transporter 2 inhibitors promote osmotic/natriuretic diuresis and reduce excess fluid volume, and this improves cardiovascular outcomes, including hospitalization for heart failure. We sought to assess the effect of empagliflozin on estimated fluid volumes in patients with type 2 diabetes and cardiovascular disease (CVD).MethodsThe study was a post-hoc analysis of the EMBLEM trial (UMIN000024502), an investigator-initiated, multi-center, placebo-controlled, double-blinded, randomized-controlled trial designed primarily to evaluate the effect of 24 weeks of empagliflozin treatment on vascular endothelial function in patients with type 2 diabetes and established CVD. The analysis compared serial changes between empagliflozin (10 mg once daily, n = 52) and placebo (n = 53) in estimated plasma volume (ePV), calculated by the Straus formula and estimated the extracellular volume (eEV), determined by the body surface area, measured at baseline and 4, 12, and 24 weeks after initiation of treatment. Correlations were examined between the changes from baseline to week 24 in each estimated fluid volume parameter and several clinical variables of interest, including N-terminal pro-brain natriuretic peptide (NT-proBNP) concentration.ResultsIn an analysis using mixed-effects models for repeated measures, relative to placebo empagliflozin reduced ePV by − 2.23% (95% CI − 5.72 to 1.25) at week 4, − 8.07% (− 12.76 to − 3.37) at week 12, and − 5.60% (− 9.87 to − 1.32) at week 24; eEV by − 70.3 mL (95% CI − 136.8 to − 3.8) at week 4, − 135.9 mL (− 209.6 to − 62.3) at week 12, and − 144.4 mL (− 226.3 to − 62.4) at week 24. The effect of empagliflozin on these parameters was mostly consistent across various patient clinical characteristics. The change in log-transformed NT-proBNP was positively correlated with change in ePV (r = 0.351, p = 0.015), but not with change in eEV.ConclusionsOur data demonstrated that initiation of empagliflozin treatment substantially reduced estimated fluid volume parameters in patients with type 2 diabetes and CVD, and that this effect was maintained for 24 weeks. Given the early beneficial effect of empagliflozin on cardiovascular outcomes seen in similar patient populations, our findings provide an important insight into the key mechanisms underlying the clinical benefit of the drug.Trial registration University Medical Information Network Clinical Trial Registry, number 000024502

N-terminal pro-brain natriuretic peptide and coronary collateral formation in patients undergoing primary percutaneous coronary intervention

There is insufficient information on the relationship between the N-terminal pro-brain natriuretic peptide (NT-proBNP) level and collateral circulation (CC) formation after primary percutaneous coronary intervention (PCI) in patients with ST-segment elevation myocardial infarction. We analyzed 857 patients who underwent primary PCI. The serum NT-proBNP levels were measured on the day of admission, and the CC was scored according to Rentrop’s classification. Log-transformed NT-proBNP levels were significantly higher in patients with good CC compared to those with poor CC (6.13 ± 2.01 pg/mL versus 5.48 ± 1.97 pg/mL, p < 0.001). The optimum cutoff value of log NT-proBNP for predicting CC was 6.04 pg/mL. Log NT-proBNP ≥ 6.04 pg/mL (odds ratio 2.23; 95% confidence interval 1.51–3.30; p < 0.001) was an independent predictor of good CC. CC development was higher in patients with a pre-TIMI flow of 0 or 1 than those with a pre-TIMI flow of 2 or 3 (22.6% versus 8.8%, p = 0.001). The incidence of left ventricular (LV) dysfunction (< 50%) was greater in patients with a pre-TIMI flow of 0 or 1 (49.8% versus 35.5%, p < 0.001). The release of NT-proBNP was greater in patients with LV dysfunction (34.3% versus 15.6%, p < 0.001). The incidence of good CC was greater in patients with log NT-proBNP levels ≥ 6.04 pg/ml (16.8% versus 26.2%, p = 0.003). The association between NT-proBNP and collateral formation was not influenced by pre-TIMI flow and LV function. NT-proBNP appears to reflect the degree of collateral formation in the early phase of STEMI and might have a new role as a useful surrogate biomarker for collateral formation in patients undergoing primary PCI.

Epicardial adipose tissue is associated with the formation of left ventricular aneurysm after myocardial infarction

Abstract Background Left ventricular aneurysm (LVA), a serious complication of transmural myocardial infarction, is generally related to poor cardiovascular outcomes. The formation of LVA is essentially an inflammatory remodeling process regulated by multiple systemic and local factors. Epicardial adipose tissue (EAT), a depot of visceral adipose tissue directly overlying the myocardium, is increasingly recognized as an important immune organ by secreting a variety of bioactive adipocytokines. However, the relation of EAT to the development of LVA is still unclear. Purpose In this study, we sought to investigate the association between EAT volume and the formation of LVA in subjects with previous myocardial infarction (MI). Methods A total of 55 subjects with previous MI and the presence of LVA, and age- and sex-matched 50 subjects with previous MI but without LVA were enrolled between October 2011 and June 2019. EAT was quantified and the presence of LVA was ascertained by cardiac magnetic resonance (CMR). EAT volume was indexed to body surface area. Results In the overall population, EAT volume index was correlated positively to log-transformed N-terminal pro-brain natriuretic peptide (NT-proBNP) levels (Pearson's r=0.332, P=0.002), and inversely to left ventricular ejection fraction (LVEF; Pearson's r=−0.240, P=0.031). The indexed EAT volume was significantly higher in subjects with than without LVA (41.10±11.73 vs. 33.25/11.70 mL/m2, P=0.003). In subjects with LVA, EAT volume index was further increased in those at older age (43.59±13.09 mL/m2 vs. 37.29±8.26 mL/m2, P=0.029) or with type 2 diabetes (43.38±12.32 mL/m2 vs. 35.20±7.67 mL/m2, P=0.013). After adjusting for sex, age and the presence of diabetes in the multivariate analysis, tertiles of EAT volume index remained significantly associated with the presence of LVA (P for trend=0. 003). Strikingly, compared to the lowest tertile (≤30.80 mL/m2), the intermediate (30.80–44.13 mL/m2) and highest (&amp;gt;44.13 mL/m2) tertiles of EAT volume index corresponded to 4.869– (95% CI 1.792–14.155, P=0.003) and 4.876– (95% CI, 1.787–14.206, P=0.003) increased risk for LVA. Conclusion Our study suggests that EAT volume is independently associated with the formation of LVA and reduced cardiac function after myocardial infarction. EAT in patients with or without LVA Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): National Natural Science Foundation of China

Possible Mechanisms Underlying Elevated Serum N-Terminal Pro-Brain Natriuretic Peptide in Healthy Japanese Subjects.

Background: The precise mechanisms underlying elevation of serum N-terminal pro-brain natriuretic peptide (NT-proBNP) in healthy subjects have not been fully clarified.Methods and Results: In 2,844 Japanese healthy subjects with serum NT-proBNP <125 pg/mL, (1) brachial-ankle pulse wave velocity and (2) second peak of the peripheral systolic blood pressure minus diastolic blood pressure (pulse pressure 2 [PP2]), as markers of cardiac afterload; (3) fibrosis 4 score (FIB-4 score, a marker of liver fibrosis), as a marker of cardiac preload; and (4) ratio of the pre-ejection time to ejection time (PEP/ET), as a marker of cardiac systolic function, were measured. At the first examination, after the adjustments, log-transformed serum NT-proBNP was associated with PP2 and FIB-4 score, but not with PEP/ET. These parameters were successfully measured again after a 3-year interval in 1,978 subjects. On Pearson’s correlation analysis, change in PP2 and FIB-4 score during the study period was significantly correlated with change in serum NT-proBNP (r=0.05, 0.09, respectively; P<0.01).Conclusions: In apparently healthy Japanese subjects, both increased cardiac preload and increased cardiac afterload, but not impaired cardiac systolic function, may be associated with elevated serum NT-proBNP.

Serum N-terminal proBNP, not troponin I, at presentation predicts long-term neurologic outcome in acute charcoal-burning carbon monoxide intoxication

Objective: This study aimed to investigate whether the serum N-terminal pro-brain natriuretic peptide (NT-proBNP) and troponin I levels at emergency department (ED) presentation predict long-term neurologic outcomes after acute charcoal-burning carbon monoxide (CO) poisoning.Methods: This retrospective study included 220 patients suffering from charcoal-burning CO poisoning. The demographics, serum NT-proBNP and troponin I levels at ED presentation, treatment, clinical course during hospitalization, and long-term neurologic outcomes were collected.Results: The median serum NT-proBNP level at presentation was 48.8 (16.5–259) pg/mL, and 78 patients (35.5%) had elevated troponin I (>0.04 ng/mL) after acute charcoal-burning CO poisoning. The upper NT-proBNP and elevated troponin I groups had higher prevalences of respiratory failure, hypotension, and myocardial injury during hospitalization and altered mentality (GCS ≤14) at discharge than the lower NT-proBNP and normal troponin I groups. The incidence of persistent severe neurologic sequelae at 25 months after acute CO poisoning was 10.9%. The upper NT-proBNP and elevated troponin I groups had a higher incidence of poor long-term neurologic outcome than the counterpart groups. Log-transformed NT-proBNP and elevated troponin I were associated with poor long-term neurologic outcome in the univariate analysis, but only the adjusted log-transformed NT-proBNP remained an independent factor in the multivariate analysis. Compared with a predictive model including previously proposed predictors, the addition of log NT-proBNP improved the diagnostic accuracy for predicting poor long-term neurologic outcome. The serum NT-proBNP values for predicting poor long-term neurologic outcome were 74.6 and 32.7 pg/mL at fixed sensitivities of 95 and 99%, respectively.Conclusions: Elevated serum NT-proBNP at ED presentation is correlated with a risk of poor long-term neurologic outcome after discharge in cases of acute charcoal-burning CO poisoning. NT-proBNP could significantly improve the risk stratification of patients who will experience poor long-term neurologic outcome after CO poisoning. This potentially valuable marker should be further validated.

Clinical implications of serum adiponectin on progression of atrial fibrillation

BackgroundThe association between circulating adiponectin levels and atrial fibrillation (AF) is uncertain. We, therefore, investigated whether an increased serum adiponectin level is implicated in the long-term recurrence of AF after ablation therapy. MethodsOur study included 100 consecutive patients (88 men; median age, 57.9±10.9 years) who underwent catheter ablation for AF at our hospital between 2011 and 2013. The adiponectin and N-terminal pro-brain natriuretic peptide (NT-proBNP) levels were measured before ablation and compared between those in whom AF recurred and those in whom AF did not recur. ResultsElevation in adiponectin levels was significantly associated with female sex, non-paroxysmal AF, heart failure, higher NT-proBNP and matrix metallo-proteinase-2 levels, and lower body mass index. After a stepwise adjustment for any potential confounding variables, the adiponectin levels remained significantly associated with female sex (beta=0.2601, P=0.0041), non-paroxysmal AF (beta=0.2708, P=0.0080), and higher NT-proBNP levels (beta=0.2536, P= 0.0138). During the median follow-up period of 26.2 months, AF recurred in 48 of the 100 patients. Stepwise multivariate adjustment showed that an increased log-transformed NT-proBNP (Hazard ratio [HR], 2.18; 95% confidence interval [CI] 1.25–4.00; P=0.0055), longer duration of AF (HR, 1.87; 95%CI 1.01–3.76; P=0.0465), and decreased left ventricular ejection fraction (HR, 0.96; 95%CI 0.93–0.99; P=0.0391) were independent predictors of recurrent AF after catheter ablation, but adiponectin was not. ConclusionsOur data indicated that adiponectin was partially responsible for progression of AF, but the correlation between adiponectin levels and AF recurrence was not significant.

A study of clinical and physiological relations of daily physical activity in precapillary pulmonary hypertension.

Daily physical activity is reduced in precapillary pulmonary hypertension (PH), but the underlying mechanisms are inadequately explored. We sought to investigate clinical and physiological relations of daily physical activity and profile differences between less and more active patients with precapillary PH. A prospective, cross-sectional study of 20 patients with precapillary PH who undertook 1) a comprehensive clinical assessment, 2) a preliminary treadmill test, 3) 7-day monitoring of daily walking intensity with triaxial accelerometry, and 4) a personalized treadmill test corresponding to the individual patient mean daily walking intensity with real-time physiological measurements. Significant clinical correlations with individual patient mean walking intensity [1.71 ± 0.27 (SD) m/s2] were observed for log-transformed N-terminal probrain natriuretic peptide (log NT-proBNP; r = -0.75, P = <.001), age (r = -0.70, P = 0.001), transfer factor for carbon monoxide %predicted (r = 0.51, P = 0.022), and 6-min walk distance (r = 0.50, P = 0.026). Significant physiological correlations were obtained for heart rate reserve (r = 0.68, P = 0.001), quadriceps tissue oxygenation index (Q-[Formula: see text]; r = 0.58, P = 0.008), change in Q-[Formula: see text] from rest (r = 0.60, P = 0.006), and ventilatory equivalent for oxygen uptake (r = -0.56, P = 0.013). Stepwise multiple regression analyses retained log NT-proBNP (R2 = 0.55), heart rate reserve (R2 = 0.44), and Q-[Formula: see text] (R2 = 0.13) accounting for a significant variance in individual walking intensity. Less active patients had greater physical activity-induced cardiopulmonary impairment, worse quadriceps oxygenation profile, and compromised health-related quality of life compared with more active patients. These preliminary findings suggest a significant relation between right ventricular and peripheral muscle oxygenation status and reduced daily physical activity in precapillary PH. Further research is warranted to unravel the physiological determinants, establish clinical predictors, and identify beneficial interventions.NEW & NOTEWORTHY Daily physical activity holds promise to be a meaningful, patient-related outcome measure in pulmonary hypertension. In this study, novel findings in a representative sample of patients with precapillary pulmonary hypertension link reduced daily walking activity, as measured by triaxial accelerometry, with compromised right ventricular and pulmonary vascular status, peripheral muscle oxygenation, and health-related quality of life, providing a preliminary insight into the physiological mechanisms and clinical predictors of daily physical activity in precapillary pulmonary hypertension.

NT-proBNP is increased in differentiated thyroid carcinoma patients and may predict cardiovascular risk

IntroductionChronic suppression of TSH in patients treated for differentiated thyroid carcinoma (DTC) may induce cardiac damage and increase risk for cardiovascular events and premature mortality. We aimed to compare circulating concentrations of N-terminal pro Brain Natriuretic Peptide (NT-proBNP) of DTC patients with controls, and to investigate whether higher NT-proBNP is associated with an increased risk for cardiovascular events and all-cause mortality in DTC patients. MethodsSerum NT-proBNP levels were determined in 266 DTC patients, median 10.4 [IQR 4.1–18.5] years after DTC diagnosis, and compared to 798 age- and sex-matched controls. Using multivariable Cox regression analyses, the association of NT-proBNP with cardiovascular events and all-cause mortality was determined. Hazard ratios (HR) and 95% confidence intervals (CIs) were expressed per SD increase of log-transformed NT-proBNP. ResultsMean age±SD of DTC patients and controls was 54.8±14.5 and 54.8±12.8years, respectively; 74% were women. Median NT-proBNP level was 70 [40–119] ng/L for DTC patients vs. 49 [25–89] ng/L for controls (p<0.001). During median follow-up of 8.6 [6.6–9.0] years, 30 DTC patients (11.4%) had a cardiovascular event and 38 (14.4%) died. Higher NT-proBNP was associated with an increased risk for cardiovascular events and all-cause mortality, age- and sex-adjusted HRs (95% CIs) 3.22 (2.17–4.79) and 1.61 (1.17–2.23), respectively. In further models with adjustment for cardiovascular risk factors, NT-proBNP remained independently associated with outcome. ConclusionNT-proBNP levels are elevated in patients with DTC, and are associated with an increased risk for cardiovascular events and all-cause mortality. Determination of NT-proBNP may identify DTC patients at increased cardiovascular risk, who could benefit from more stringent cardiovascular risk surveillance.

Impaired left ventricular global longitudinal strain in patients with heart failure with preserved ejection fraction: insights from the RELAX trial.

While abnormal left ventricular (LV) global longitudinal strain (GLS) has been described in patients with heart failure with preserved ejection fraction (HFpEF), its prevalence and clinical significance are poorly understood. Patients enrolled in the RELAX trial of sildenafil in HFpEF (LV ejection fraction ≥50%) in whom two-dimensional, speckle-tracking LV GLS was possible (n = 187) were analysed. The distribution of LV GLS and its associations with clinical characteristics, LV structure and function, biomarkers, exercise capacity and quality of life were assessed. Baseline median LV GLS was -14.6% (25th and 75th percentile, -17.0% and -11.9%, respectively) and abnormal (≥ - 16%) in 122/187 (65%) patients. Patients in the tertile with the best LV GLS had lower N-terminal pro-brain natriuretic peptide (NT-proBNP) [median 505 pg/mL (161, 1065) vs. 875 pg/mL (488, 1802), P = 0.008) and lower collagen III N-terminal propeptide (PIIINP) levels [median 6.7 µg/L (5.1, 8.1) vs. 8.1 µg/L (6.5, 10.5), P = 0.001] compared with the tertile with the worst LV GLS. There was also a modest linear relationship with LV GLS and log-transformed NT-proBNP and PIIINP (r = 0.29, P < 0.001 and r = 0.19, P = 0.009, respectively). We observed no linear association of LV GLS with Minnesota Living with Heart Failure scores, 6-min walk distance, peak oxygen consumption, or expiratory minute ventilation/carbon dioxide excretion slope. Impaired LV GLS is common among HFpEF patients, indicating the presence of covert systolic dysfunction despite normal LV ejection fraction. Impaired LV GLS was associated with biomarkers of wall stress and collagen synthesis and diastolic dysfunction but not with quality of life or exercise capacity, suggesting other processes may be more responsible for these aspects of the HFpEF syndrome.

Feasibility and predictors of early discharge after percutaneous edge-to-edge mitral valve repair

BackgroundPercutaneous edge-to-edge mitral valve repair (PMVR) recently emerged as an effective treatment modality for patients with severe mitral regurgitation (MR). Length of postprocedural hospital stay may represent a modifiable cost...

Factors affecting N-terminal pro-brain natriuretic peptide elevation in the acute phase of Kawasaki disease.

The aim of this study was to investigate the clinical significance and factors that affect N-terminal pro-brain natriuretic peptide (NT-proBNP) elevation in the acute phase of Kawasaki disease (KD) despite the absence of apparent cardiac complications. The laboratory and echocardiography results of 44 KD patients in the acute and subacute phases were reviewed. With preserved cardiac function, median NT-proBNP was significantly elevated in the acute phase compared with the subacute phase (343 pg/mL, IQR, 162-1182 pg/mL vs 98 pg/mL, IQR, 61-205 pg/mL, respectively; P < 0.0001). The respective levels of tumor necrosis factor (TNF)-α, soluble TNF receptor (sTNFR)1, and sTNFR2 were also significantly elevated in the acute phase compared with the subacute phase: TNF-α, 3.3 pg/mL (IQR, 2.6-4.8 pg/mL) versus 2.4 pg/mL (IQR 1.9-4.0 pg/mL; P < 0.01), sTNFR1, 2741 pg/mL (IQR, 2080-3183 pg/mL) versus 976 pg/mL (IQR, 814-1247 pg/mL; P < 0.0001), sTNFR2, 5644 pg/mL (IQR, 4693-7520 pg/mL) versus 3169 pg/mL (IQR, 2132-3878 pg/mL; P < 0.0001). Log-transformed NT-proBNP was correlated with TNF-α (r = 0.29, P = 0.056), sTNFR1 (r = 0.60, P < 0.0001), and sTNFR2 (r = 0.65, P < 0.0001). TNF-α was correlated with sTNFR1 (r = 0.35, P = 0.02) and sTNFR2 (r = 0.51, P < 0.001). Tumor necrosis factor-α may cause NT-proBNP elevation in the acute phase of KD, and NT-proBNP level may be an indicator of TNF-α activity.

Serial measurements of N-terminal pro-brain natriuretic peptide in patients with coronary heart disease.

ObjectiveTo assess the prognostic value of 12-months N-Terminal Pro-Brain Natriuretic Peptide (NT-proBNP) levels on adverse cardiovascular events in patients with stable coronary heart disease.MethodsNT-proBNP concentrations were measured at baseline and at 12-months follow-up in participants of cardiac rehabilitation (median follow-up 8.96 years). Cox-proportional hazards models evaluated the prognostic value of log-transformed NT-proBNP levels, and of 12-months NT-proBNP relative changes on adverse cardiovascular events adjusting for established risk factors measured at baseline.ResultsAmong 798 participants (84.7% men, mean age 59 years) there were 114 adverse cardiovascular events. 12-months NT-proBNP levels were higher than baseline levels in 60 patients (7.5%) and numerically more strongly associated with the outcome in multivariable analysis (HR 1.65 [95% CI 1.33–2.05] vs. HR 1.41 [95% CI 1.12–1.78], with a net reclassification improvement (NRI) of 0.098 [95% CI 0.002–0.194] compared to NRI of 0.047 [95% CI −0.0004–0.133] for baseline NT-proBNP levels. A 12-month 10% increment of NT-proBNP was associated with a HR of 1.35 [95% CI 1.12–1.63] for the onset of an adverse cardiovascular event. Subjects with a 12-month increment of NT-proBNP had a HR of 2.56 [95% CI 1.10–5.95] compared to those with the highest 12-months reduction.ConclusionsTwelve-months NT-proBNP levels after an acute cardiovascular event are strongly associated with a subsequent event and may provide numerically better reclassification of patients at risk for an adverse cardiovascular event compared to NT-proBNP baseline levels after adjustment for established risk factors.

An elevated level of N-terminal pro-brain natriuretic peptide is associated with the development of good collateral circulation in patients undergoing primary percutanous coronary intervention?

Purpose: Although N-terminal pro-brain natriuretic peptide (NT-proBNP) is released by ventricular myocardium as a result of increased myocardial wall stress, NT-proBNP was recently demonstrated to be a potential stimulator of angiogenesis. However, little is known about the correlation between NT-proBNP level and collateral formation in patients undergoing primary percutaneous coronary intervention (PCI) after ST segment elevation myocardial infarction (MI). Methods: Between November 2005 and November 2011, 857 eligible patients (634 men; mean age = 62.8±12.0 year-old) were analyzed in this study. Serum NT-proBNP levels were measured at the time of admission. Collateral circulation (CC) was graded according to Rentrop's classification. Grade 0 and 1 are regarded as poor, and grade 2 and 3 are regarded as good CC. Results: Overall, 429 (50.1%) had angiographic evidence of CC including 265 (30.9%) with grade 1 and 164 (19.1%) with grade 2/3. The patients with good CC had a more typical chest pain, preinfarction angina, previous coronary heart disease (CHD), non-left anterior descending artery (LAD)-related MI, multivessel disease, pre-TIMI flow grade 0/1, and longer symptom-to-door (STD) time. Log-transformed NT-proBNP level was positively correlated with Rentrop collateral score (r=0.148, p<0.001) and left ventricular end-systolic volume (LVESV; r=0.156, p<0.001), and negatively correlated with LV ejection fraction (EF; r=-0.320, p<0.001). Log-transformed NT-proBNP levels were significantly higher in patients with grade 2/3 CC (6.13±2.01 pg/mL) compared with grade 1 (5.68±2.04 pg/mL) and grade 0 CC (5.36±1.91 pg/mL), respectively (p for trend <0.001). There were no significant differences between good CC and poor CC when compared with LVEF and LVESV. In the receiver-operator characteristic curve of log NT-proBNP, the area under the curve of log NT-proBNP for predicting CC was 0.600 (sensitivity 54.9% and specificity 64.8%), and optimum cut-off value was 6.04 pg/mL. In multivariate logistic regression model, log-transformed NT-proBNP ≥6.04 pg/mL (Odds ratio [OR] 2.123; 95% confidence interval [CI] 1.423–3.168) in addition to previous CHD (OR 1.835, 95% CI 1.056-3.187), pre-TIMI flow grade 0/1 (OR 3.080, 95% CI 1.804-5.257), non-LAD-related MI (OR 2.102, 95% CI 1.443-3.062) was an independent predictor of good CC after adjusting for confounding variables. Conclusions: An elevated level of serum NT-proBNP is independently associated with collateral development in patients undergoing primary PCI. Further studies are required to elucidate mechanism of these associations.

Relationships between cardiac resynchronization therapy and N-terminal pro-brain natriuretic peptide in patients with heart failure and markers of cardiac dyssynchrony: an analysis from the Cardiac Resynchronization in Heart Failure (CARE-HF) study

The Cardiac Resynchronization in Heart Failure (CARE-HF) study showed that cardiac resynchronization therapy (CRT) reduces mortality in HF patients with markers of dyssynchrony. Plasma N-terminal pro-brain natriuretic peptide (NT-proBNP) might predict which patients benefit most from CRT. We evaluated whether the prognostic value of NT-proBNP was influenced by CRT and the effects of CRT stratified according to NT-proBNP. A total of 813 patients were enrolled in CARE-HF. Baseline log-transformed NT-proBNP independently predicted all-cause mortality, sudden death, and death from pump failure. In a multivariable model including log-transformed NT-proBNP, assignment to CRT remained independently associated with better prognosis without evidence of interaction. Stratifying patients according to the median NT-proBNP and to CRT treatment allocation, all-cause mortality was 12% if <median + CRT, 25% if <median + control group, 35% if >or= median + CRT, and 51% if >or= median + control group. There was no evidence of a difference in the relative effect of CRT across different values of NT-proBNP. NT-proBNP retains its prognostic value in HF patients with CRT. Deploying CRT before the patients have reached end-stage HF may maximize the benefit of treatment.

Association between Changes in N-Terminal Pro-Brain Natriuretic Peptide Levels and Changes in Left Ventricular Mass Index in Stable Hemodialysis Patients

Background/Aims: Left ventricular (LV) hypertrophy is a powerful predictor of mortality in dialysis patients. Serial measurements of LV mass provide prognostic information. We evaluated the association between changes in biomarkers and changes in LV mass index (LVMI) in hemodialysis (HD) patients. Methods: This was a prospective study of 21 stable HD patients with preserved LV ejection fraction (≧50%). Echocardiography and measurements of N-terminal pro-brain natriuretic peptide (NT-proBNP), brain natriuretic peptide (BNP) and cardiac troponin T were performed on the same day and repeated 6 and 12 months later. Results: At baseline, the NT-proBNP and BNP levels correlated with LVMI. Percent changes in LVMI were positively associated with those in log-transformed NT-proBNP levels during both the first (baseline vs. month 6, r = 0.78, p < 0.001) and the second 6 months (months 6 vs. 12, r = 0.73, p < 0.001). Among the 3 biomarkers, NT-proBNP was the only one that was related to changes in LVMI by multivariate correlation analysis, including age, sex, blood pressure, predialysis weight and use of angiotensin-converting enzyme inhibitor or angiotensin II receptor blocker. Conclusion: Our results show that changes in LVMI are closely correlated with variation in NT-proBNP levels in HD patients. These data have significant implications for the application of NT-proBNP as a biomarker for assessing changes in LVMI in HD patients.