Baseline N-terminal Pro-brain Natriuretic Peptide Research Articles

Elevation in high-sensitivity troponin T in heart failure and preserved ejection fraction and influence of treatment with the angiotensin receptor neprilysin inhibitor LCZ696.

Elevated high-sensitivity troponin is associated with increasing disease severity in patients with stable heart failure with reduced ejection fraction, but less is known about the association in heart failure with preserved ejection fraction. We examined the prevalence of elevated high-sensitivity troponin T (hs-TnT) in 298 patients with heart failure with preserved ejection fraction enrolled in the Prospective comparison of angiotensin receptor neprilysin inhibitor with angiotensin receptor blocker on Management Of heart failUre with preserved ejectioN fracTion (PARAMOUNT) trial, in which the angiotensin receptor neprilysin inhibitor LCZ696 reduced markers of heart failure severity compared with valsartan. We assessed the association between hs-TnT and cardiac structure and function, and the effect of LCZ696, compared with valsartan, on hs-TnT over 36 weeks. Elevated hs-TnT in the myocardial injury range (>0.014 μg/L) was found in 55% of patients and was associated with older age, history of diabetes mellitus, higher N-terminal pro-brain natriuretic peptide, lower estimated glomerular filtration rate, and larger left atrial size, left ventricular volume, and mass. LCZ696 treatment reduced hs-TnT to a greater extent at 12 weeks (12% reduction; P=0.05) and at 36 weeks (14% reduction; P=0.03) compared with valsartan. Troponin T was elevated in a substantial number of patients enrolled in a heart failure with preserved ejection fraction clinical trial and was associated with abnormalities of cardiac structure, function, and elevated baseline N-terminal pro-brain natriuretic peptide. Decreases in hs-TnT with LCZ696 in parallel with improvement in N-terminal pro-brain natriuretic peptide and left atrial size suggest that the angiotensin receptor neprilysin inhibitor LCZ696 may reduce this measure of myocardial injury in heart failure with preserved ejection fraction. http://www.clinicaltrials.gov. Unique identifier: NCT00887588.

Early Trends in N-Terminal Pro–Brain Natriuretic Peptide Values After Left Ventricular Assist Device Implantation for Chronic Heart Failure

Left ventricular assist devices (LVADs) acutely decrease left ventricular wall stress. Thus, early postoperative levels of N-terminal pro-brain natriuretic peptide (NT-proBNP) should decrease. This study investigated postoperative changes in NT-proBNP levels, the parameters related to changes, and the possible association with complications by performing a retrospective analysis of changes in daily NT-proBNP (pg/ml) levels from admission to discharge both before and after LVAD implantation in a tertiary referral center. For 72 patients implanted with HeartMate II LVADs, baseline NT-proBNP levels were elevated at 3,943 ng/ml (interquartile range 1,956 to 12,964). Preoperative stabilization led to marked decreases in NT-proBNP. Levels peaked 3 days after surgery and subsequently decreased. Patients with complicated postoperative courses had higher early postoperative elevations. By discharge, NT-proBNP decreased markedly but was still 2.83 (1.60 to 5.76) times the age-based upper limit of normal. The 26% reduction in NT-proBNP between admission and discharge was due mostly to the preoperative reductions and not those induced by the LVAD itself. The decrease was not associated with decreases in LV volume. In conclusion, preoperative treatment reduces NT-proBNP values. The magnitude of early postoperative changes is related to the clinical course. Levels at discharge remain markedly elevated and similar to values after preoperative stabilization despite presumptive acute LV unloading.

Usefulness of N-Terminal Pro-Brain Natriuretic Peptide Levels to Predict Success of Weaning from Intra-Aortic Balloon Pumping

There is currently no reliable method of predicting the success of weaning from intra-aortic balloon pumping (IABP). The aim of this study was to investigate the ability of serum N-terminal pro-brain natriuretic peptide (NT-proBNP) level to predict the success of weaning from IABP. Consecutive patients scheduled for weaning from IABP were prospectively enrolled. NT-proBNP levels were measured at baseline (before the start of weaning) and cessation (just before cessation of IABP). Changes in NT-proBNP level between baseline and cessation were analyzed in 2 groups of patients: those who were successfully weaned and those who were not successfully weaned for any reason, including a decision to discontinue weaning, worsening of pulmonary edema after cessation of IABP, or unstable hemodynamics after cessation of IABP. A total of 30 patients were enrolled (mean age 66 ± 12 years, 16 men, 16 with acute myocardial infarctions, and 14 with acute exacerbation of chronic heart failure). Median (interquartile range) baseline NT-proBNP levels were not significantly different between the successful and unsuccessful weaning groups (4,200 [1,400 to 8,752] pg/ml vs (5,620 [2,035 to 13,950] pg/ml, p = 0.30). In the unsuccessful weaning group, the median NT-proBNP level was significantly higher at cessation (9,995 [2,920 to 15,100] pg/ml) than at baseline (p = 0.008). All patients with decreases in NT-proBNP level between baseline and cessation were successfully weaned from IABP. In conclusion, these results show that NT-proBNP levels were useful for predicting the success of weaning from IABP. If the NT-proBNP level increases during weaning from IABP, more intense management should be considered.

N-Terminal Pro-Brain Natriuretic Peptide Level is Associated With Severity and Complexity of Coronary Atherosclerosis in Patients With Acute Coronary Syndrome.

N-terminal pro-brain natriuretic peptide (NT-proBNP) levels are associated with short- and long-term mortality in acute coronary syndrome (ACS). We investigated whether baseline NT-proBNP levels are associated with burden of coronary atherosclerosis assessed by SYNTAX score (SXScore). We enrolled 509 patients with ACS who underwent coronary angiography. The patients were divided into tertiles according to the SXScore: low SXScore (≤ 22), intermediate SXScore (23-32), and high SXScore (≥ 33). The NT-proBNP levels demonstrated an increase from low SXScore tertile to high SXScore tertile. The NT-proBNP levels according to the SXScore tertiles are as follows: low and intermediate (median 635 vs 1635, P = .014), low and high (median 635 vs 4568, P < .001), and intermediate and high (median 1635 vs 4568, P < .001). In multivariate analysis, NT-proBNP remained an independent predictor of high SXScore (odds ratio: 2.688, 95% confidence interval: 1.315-5.494, P = .007) together with age (P = .002), neutrophil-lymphocyte ratio (P = .017), and presence of non-ST-segment elevation ACS (P = .002). The NT-proBNP was independently associated with burden of coronary atherosclerosis in patients with ACS.

AB0321 IL-6 Blockade Reduces Circulating N-Terminal Pro-Brain Natriuretic Peptide Levels in Patients with Active Rheumatoid Arthritis

BackgroundPatients with rheumatoid arthritis (RA) have a 1.5–2.0 fold higher risk of developing congestive heart failure than the general population. Small increases in N-terminal pro-brain natriuretic peptide (NT-proBNP) levels predict...

Association between N-terminal pro-brain natriuretic peptide levels and contrast-induced nephropathy in patients undergoing percutaneous coronary intervention for acute coronary syndrome.

Contrast-induced nephropathy (CIN) is associated with significantly increased morbidity and mortality after percutaneous coronary intervention (PCI). Patients with acute coronary syndrome (ACS) are at higher risk for CIN. N-terminal pro-brain natriuretic peptide (NT-proBNP) is closely linked to the prognosis as a strong predictor of both short- and long-term mortality in patients with ACS. We hypothesized that NT-proBNP levels on admission can predict the development of CIN after PCI for ACS. A total of 436 patients (age 62.27 ± 13.01 years; 64.2% male) with ACS undergoing PCI enrolled in this study. Admission NT-proBNP levels were measured before PCI. Serum creatinine values were measured before and within 72 hours after the administration of contrast agents. Patients were divided into 2 groups: CIN group and no-CIN group. CIN was defined as an increase in serum creatinine level of ≥0.5 mg/dL or ≥25% above baseline within 72 hours after contrast administration. CIN developed in 63 patients (14.4%). Baseline NT-proBNP levels were significantly higher in patients who developed CIN compared to those who did not develop CIN (median 774 pg/mL, interquartile range 177.4-2184 vs median 5159 pg/mL, interquartile range 2282-9677, respectively; P < 0.001). Multivariate analysis found that NT-proBNP (odds ratio [OR]: 3.448, 95% confidence interval [CI]: 1.394-8.474, P = 0.007) and baseline creatinine (OR: 6.052, 95% CI: 1.860-19.686, P = 0.003) were independent predictors of CIN. Admission NT-proBNP level is an independent predictor of the development of CIN after PCI in ACS.

Early NT-proBNP decrease with ivabradine in ambulatory patients with systolic heart failure.

Heart rate (HR) reduction in patients with systolic heart failure (HF) is a cornerstone of current therapy. The aim of this study was to evaluate the short-term effect of the HR reduction with ivabradine on N-terminal pro-brain natriuretic peptide (NT-proBNP) in outpatients with systolic HF. Ivabradine improves survival and promotes left ventricle remodelling by reducing resting heart rate. Nt-ProBNP absolute and trends predict prognosis. We hypothesized a possible association between heart rate decrease and Nt-ProBNP values. We included 25 outpatients with systolic HF on optimized medical therapy (80% on angiotensin-converting enzyme inhibitors, 56% on spironolactone, and 88% on β-blocker therapy), left ventricle ejection fraction <40%, and sinus rhythm and HR >70/bpm. After a 1 month running-out period, to establish the clinical and NT-proBNP stability, patients were started on ivabradine for 3 months. Ivabradine decreased NT-proBNP (P = 0.002) from a median of 2850 pg/mL to 1802 pg/mL, corresponding to a median absolute and percent decrease of 964 pg/mL and 44.5%, respectively. The baseline HR correlated significantly with the baseline NT-proBNP (rs = 0.411, P = 0.041). The absolute and percent HR decrease correlated with the absolute NT-proBNP decrease (rs = 0.442, P = 0.027; rs = 0.395, P = 0.05). The greater the NT-proBNP absolute decrease tertile, the greater the baseline HR (P = 0.023) and the absolute (P = 0.028) and percent (P = 0.064) HR variation. In outpatients with systolic HF, the NT-proBNP reduction obtained by short-term ivabradine treatment correlates closely with the degree of HR reduction.

N-Terminal Pro-Brain Natriuretic Peptide and Short-Term Mortality After Ischemic Stroke

Background: N-terminal pro-brain natriuretic peptide (NT-proBNP) levels are frequently elevated in patients with acute ischemic stroke. This study investigated whether the baseline NT-proBNP level on admission can predict short-term mortality after ischemic stroke. Methods: One hundred patients with acute ischemic stroke underwent thorough clinical and laboratory evaluation, including serum NT-proBNP measurement. Results: A total of 7% of patients died within 1 week after stroke onset. The NT-proBNP levels were significantly higher among the patients who died compared to NT-proBNP levels in the survivors ( P = .002). The optimal NT-proBNP cut-off point for predicting mortality was 1330 pg/mL. Multivariate analysis demonstrated that NT-proBNP concentration was an independent predictor of short-term post-stroke mortality ( P = .03). Conclusion: Increased NT-proBNP level was significantly and independently correlated with short-term mortality in patients after ischemic stroke. * BNP : brain natriuretic peptide; NT-proBNP : N-terminal pro-brain natriuretic peptide; CT : computed tomographic; MRI : magnetic resonance imaging; NIHSS : National Institutes of Health Stroke Scale; TOAST : Trial of Org 10172 in Acute Stroke Treatment; ROC : receiver operating characteristic

THU0059 Reduction of inflammation with abatacept and tocilizumab results in lower N-terminal pro brain natriuretic peptide levels in patients with rheumatoid arthritis: Results from two prospective cohort studies

BackgroundRheumatoid arthritis (RA) patients are at increased risk of heart failure (HF). The chronic inflammatory state in RA is associated with increased levels of N-terminal pro-brain natriuretic peptide (NT-proBNP), a...

Performance Trends and Cardiac Biomarkers in a 30-km Cross-Country Race, 1993–2007

Long-distance running events enjoy increasing popularity in all ages. Whereas the health benefits of regular moderate exercise are undisputed, the net health effects of single or repeated participation in endurance events of marathon type remain to be determined. We wanted to investigate performance trends over time and the relationship between race performance and cardiac biomarker levels among participants in a large annual 30-km cross-country race. We analyzed a database containing age, gender, run times, and previous race participation of 124,608 runners finishing the Lidingöloppet (30 km) between 1993 and 2007. In 249 male runners age ≥ 45 yr, we also performed a thorough cardiovascular examination, including measuring the cardiac biomarkers N-terminal pro-brain natriuretic peptide (NT-proBNP) and troponin. Total participation increased 56% with the largest gains in younger female and older male runners. Mean run times rose from 164 ± 27 min in 1993 to 184 ± 33 min in 2007 (P < 0.001) in men and from 179 ± 26 to 203 ± 32 in women (P < 0.001) after a strong linear relationship (men, r = 0.98; women, r = 0.93). Increased run times were seen in the mean, top, and bottom quartiles as well as in the top and bottom 5% of all age and gender groups. In the substudy among 249 older male runners, not only higher body mass index, older age, and fewer previous race participations but also higher baseline NT-proBNP was independently associated with increased run time. Whereas participation in the Lidingöloppet increased, fitness deteriorated over time in both genders and in all ages. In a subset of older male athletes, longer run times were associated with higher levels of NT-proBNP. The present findings may support the usefulness of preparticipation evaluation to ensure appropriate fitness and cardiovascular health in long-distance race participants.

Altered ventriculo-arterial coupling during exercise in athletes releasing biomarkers after endurance running

Exercise can lead to release of biomarkers such as cardiac troponin T (cTnT) and N-terminal pro-brain natriuretic peptide (NT-proBNP), a poorly understood phenomenon proposed to especially occur with high-intensity exercise in less trained subjects. We hypothesised that haemodynamic perturbations during exercise are larger in athletes with cTnT release, and studied athletes with detectable cTnT levels after an endurance event (HIGH; n=16; 46±9years) against matched controls whose levels were undetectable (LOW; n=11; 44±7years). Echocardiography was performed at rest and at peak supine bicycle exercise stress. Left ventricular (LV) end-systolic elastance (E (LV) a load-independent measure of LV contractility), effective arterial elastance (E (A) a lumped index of arterial load) and end-systolic meridional wall stress were calculated from cardiac dimensions and brachial blood pressure. Efficiency of cardiac work was judged from the ventriculo-arterial coupling ratio (E (A)/E (LV): optimal range 0.5-1.0). While subgroups had similar values at rest, we found ventriculo-arterial mismatch during exercise in HIGH subjects [0.47 (0.39-0.58) vs. LOW: 0.73 (0.62-0.83); p<0.01] due to unopposed increase in E (LV) (p<0.05). In LOW subjects, a greater increase occurred in E (A) during exercise (+81±67% vs. HIGH: +39±32%; p=0.02) which contributed to a maintained coupling ratio. Subjects with higher baseline NT-proBNP had greater systolic wall stress during exercise (R (2)=0.39; p<0.01) despite no correlation at rest (p=ns). In conclusion, athletes with exercise-induced biomarker release exhibit ventriculo-arterial mismatch during exercise, suggesting non-optimal cardiac work may contribute to this phenomenon.

Perioperative Serum Brain Natriuretic Peptide and Cardiac Troponin in Elective Intracranial Surgery

There are some intracranial insults which are associated with cardiac abnormalities. Studies of these abnormalities have never been carried out in elective intracranial neurosurgery for the removal of brain tumors. Our prospective study aims at quantifying serum cardiac troponin T (cTnT) and N-terminal pro-brain natriuretic peptide (NT-proBNP) before and after elective intracranial neurosurgery for tumor resection in patients with no history of cardiac abnormality. Pre- and postoperative serum cTnT and NT-proBNP were measured in 108 patients submitted to elective major intracranial surgery for the removal of neoplastic lesions. We tested potentially predictive models for these biomarker serum levels. cTnT was undetectable both before and after surgery. Median (IQR) basal NT-proBNP was 35 (18-69) pg/mL and 110 (51-191) pg/mL after surgery. In a multiple linear regression model, basal NT-proBNP was predicted by age, gender, BMI, and the presence of "mass effect" (midline shift or effaced perimesencephalic cisterns on preoperative CT scan) (whole model P < 0.0001; R (2) = 0.3502; and Adjusted R (2) = 0.3247). Postoperative NT-proBNP increase was predicted by baseline NT-proBNP level (whole model P < 0.0001; R (2) = 0.5106; and Adjusted R (2) = 0.5052). An intracranial mass effect is associated with higher NT-proBNP serum levels in patients with a brain neoplasm. Following elective intracranial surgery for brain tumor resection NT-proBNP values increase.

Red cell distribution width as a marker of impaired exercise tolerance in patients with chronic heart failure

Exercise intolerance predicts mortality in patients with chronic heart failure (CHF). Recently, increased red cell distribution width (RDW) has emerged as an additional powerful predictor of poor outcome. We investigated the relationship between RDW and exercise capacity in patients with CHF. In addition, the association between training-induced improved maximal aerobic capacity (VO(2)peak) and RDW was studied. Stable and optimally treated CHF patients (n = 118) with a left ventricular ejection fraction (LVEF) <40% were included. RDW and cardiopulmonary exercise testing were obtained at baseline and after 6 months of exercise training (n = 71) or a sedentary lifestyle (n = 47). At baseline, log[RDW] was inversely related to VO(2)peak (P = 0.003), independently of disease severity [LVEF, New York Heart Association class, N-terminal pro brain natriuretic peptide (NT-proBNP)] and haemoglobin. Exercise training was associated with a decrease in RDW compared with controls (P < 0.0001 for interaction), independent of baseline VO(2)peak, haemoglobin, and NT-proBNP levels. The change in RDW after 6 months was significantly related to the change in VO(2)peak (r= -0.248, P = 0.009). Higher RDW is independently related to impaired exercise capacity in CHF patients. Increased VO(2)peak following exercise training relates to the observed changes in RDW. Whether increased RDW is a marker of impaired exercise tolerance, or plays a pathophysiological role in impaired oxygen transport, deserves further investigation.

Prognostic Value of Baseline Plasma Amino-Terminal Pro-Brain Natriuretic Peptide and Its Interactions With Irbesartan Treatment Effects in Patients With Heart Failure and Preserved Ejection Fraction

Plasma concentrations of natriuretic peptides (NPs) are associated with morbidity and mortality in patients with systolic heart failure (HF). However, the role of NP as a prognostic marker in patients with HF and preserved ejection fraction (HFpEF) has not been studied in a large cohort of well-characterized patients. Moreover, it is unclear whether treatments have a differential effect on morbidity and mortality across the spectrum of NP levels. N-terminal pro-brain natriuretic peptide (NT-proBNP) was measured at baseline in 3480 patients in the I-PRESERVE (Irbesartan in Heart Failure with Preserved Ejection Fraction Trial). In a multivariable Cox regression model, NT-proBNP above the median of 339 pg/mL was independently associated with an increased risk of the primary end point of all-cause mortality and prespecified cardiovascular hospitalizations (adjusted hazard ratio [HR], 1.79; 95% CI, 1.56 to 2.10; P<0.001); all-cause mortality (adjusted HR, 2.04; 95% CI, 1.68 to 2.47; P<0.001); and a composite of HF events, including death due to worsening HF or sudden death or hospitalization due to worsening HF (adjusted HR, 1.77; 95% CI, 1.43 to 2.20; P<0.001). There were significant interactions between the effect of irbesartan and median split of baseline NT-proBNP for the primary outcome (P=0.005), all-cause mortality (P=0.05), and the HF composite outcome (P<0.001). Use of irbesartan was associated with improved outcomes in patients with NT-proBNP below, but not above, the median. After adjusting for 20 baseline covariates, irbesartan still had a beneficial effect on the primary outcome (HR, 0.74; 95% CI, 0.60 to 90; P=0.003), all-cause mortality (HR, 0.75; 95% CI, 0.56 to 0.99; P=0.046), and HF composite outcome (HR, 0.57; 95% CI, 0.41 to 0.80; P=0.001) in patients with NT-proBNP below the median. The unexpected benefit of irbesartan in lower-risk patients with HFpEF in this post hoc analysis may indicate effects on early, but not later, high-risk stages of the disease. These findings question the strategy of using elevated plasma concentrations of NP as a patient selection criterion in HFpEF trials. More studies are needed to support or contest this practice. Clinical Trial Registration- URL: http://www.clinicaltrials.gov. Unique identifier: NCT00095238.

Systemic Diseases

Therapy of AL amyloidosis (or Ig light-chain amyloidosis), with renal involvement in most patients, remains a major challenge. An editorial recently written by an expert in that field, Dr. M.A. Gertz, has a provocative title: “I don't know how to treat amyloidosis” (1). There are good reasons for pessimism; there are also good reasons for hope. Heher et al. stress the latter point of view in their review article (2). In their conclusions, they state that: “Wider use of kidney biopsy to identify monoclonal protein deposition in patients with mild degrees of kidney dysfunction may be indicated as therapeutic options improve.” The regimen of melphalan and dexamethasone is now widely considered the standard for patients who do not receive stem-cell transplants. The study performed in Pavia, Italy, demonstrated a progression-free survival of 3.8 years and median overall survival of 5.1 years (3). The results of trials in AL amyloidosis are very heterogeneous because the mix of patients is very important in determining overall outcome (1). Indeed prognosis depends of age, proportion of patients with cardiac involvement, and the number of organs involved. The major predictor of survival in AL amyloidosis is the extent of cardiac involvement, and this can be estimated by measurement of cardiac troponin-T and NT-proBNP (N-terminal-probrain natriuretic peptide). In selected patients (younger age without significant organ dysfunction) high-dose melphalan with stem-cell transplantation may be associated with higher complete response and extended survival (4). There is a need for effective treatment of patients with symptomatic heart involvement and of patients with refractory disease. This is the goal of the retrospective study performed by Kastritis et al. from three centers where 94 patients with AL amyloidosis were managed. Bortezomib (B), which is a reversible proteasome inhibitor, has been used. This drug has shown significant activity in patients with myeloma in relapsed or refractory settings and also as a first-line treatment. Plasma cells produce amyloidogenic light chains that lead to increases in endoplasmic stress and are largely dependent on proteasome function. Amyloidogenic light chains also have a direct toxic effect on cardiomyocytes. In AL amyloidosis patients, B was prescribed at various doses in this multicenter retrospective study. However B was the first-line therapy in 19% of the patients at 1.3 mg/m2 on days 1, 4, 8, and 11, with dexamethasone at 40 mg on days 1 through 4 every 21 days. Eleven percent of patients received B without dexamethasone. Among the 94 patients analyzed, 76 (81%) had at least one prior therapy and 51% had refractory disease. The heart was involved in 73% and the kidneys were involved in 75% (11 [12%] were dialysis-dependent). A hematologic response was achieved in an average of 72% of patients. A complete response was more frequent in previously untreated patients and in those who received B twice weekly. A heart response was found in 29% of 69 patients, and a kidney response was found in 19% of 70 patients, strongly associated with hematologic response. All cardiac responders were alive after a median of 18 months. A drop in NT-proBNP accompanied cardiac response. The rates of renal responses were somewhat low, probably because of long-standing disease responsible for irreversible renal damage. The renal response may need longer follow-up because up to 25% of patients respond after >12 months. Of importance, renal impairment (even ESRD) was not associated with increased toxicity of B. After a median follow-up of 12 months (range 0.6 to 48 months), 49% of patients had either hematologic or organ progression or died. Twenty-five patients (26%) died; 1-year survival was 76% and cardiac involvement was independently associated with survival. In patients with renal impairment but not undergoing dialysis, only baseline NT-proBNP was significantly associated with survival. In the whole population of patients (excluding dialysis patients), only NT-proBNP and hematologic responses were independently associated with survival. The most common nonhematologic toxicities were peripheral sensory neuropathy (40%) with or without neuropathic pain, exacerbation of orthostatic hypotension (36%), peripheral edema, and intestinal manifestations. This paper shows that B is an effective and rapidly acting treatment: median of 28 days versus 2 to 4 months in dexamethasone-based regimens. As first-line therapy, B achieves a 47% complete remission rate. It also shows activity even in heavily pretreated or refractory patients. However, it should not be used in patients with severe symptomatic heart failure because of the high rate of adverse events (5). New therapeutic possibilities emerged recently in AL amyloidosis after recent advances in myeloma treatment. The tolerance of lenalidomide in a small trial in patients with severe AL amyloidosis has been poor (6). Incorporation of B in the first-line treatment, particularly in high-risk patients, should be investigated in phase III trials.

Age-related short-term effect of ramipril on N-terminal pro-brain natriuretic peptide and markers of hemostasis in patients after acute myocardial infarction

Angiotensin-converting enzyme (ACE) inhibitors after acute myocardial infarction (MI) prevent heart failure and recurrent ischemic events. Our aim was to evaluate the effect of ramipril on N-terminal pro-brain natriuretic peptide (NT-proBNP) and on markers of hemostasis, including plasminogen-activator-inhibitor-1 (PAI-1), von Willebrand factor (vWF), factor VIII (FVIII) and fibrinogen, in patients after acute MI, with emphasis on those over 55 years of age. In this prospective, single-center, observational study 38 patients were treated with ramipril after the first Q-wave MI. Markers of hemostasis and NT-proBNP were estimated before and two weeks after ramipril treatment. Significant differences were observed in PAI-1 and NT-proBNP levels in patients over 55 years. In this age group the mean PAI-1 level decreased significantly after ramipril therapy (3.6 +/- 1.25 U/ml vs. 2.65 +/- 1.4 U/ml, P = 0.011) and was significantly lower than in younger (<55 years) patients (2.65 +/- 1.4 U/ml vs. 4.39 +/- 1.7 U/ml, P = 0.002). In addition, in the older patients the mean baseline NT-proBNP level was significantly higher than in the younger age group (258.35 +/- 347.6 pmol/l vs. 17.1 +/- 22 pmol/l, P = 0.028) and was also higher after ramipril therapy (240.5 +/- 254.3 pmol/l vs. 67.3 +/- 75.2 pmol/l, P = 0.034). In the younger patients, mean NT-proBNP after short-term ramipril therapy increased significantly in comparison with baseline (67.3 +/- 75.2 pmol/l vs. 17.15 +/- 22.0 pmol/l, P = 0.046). In acute Q-wave MI, increased PAI-1 levels, but not increased NT-proBNP, respond rapidly to early ACE inhibition by ramipril in patients over 55 years of age but not in younger patients.

Bortezomib With or Without Dexamethasone in Primary Systemic (Light Chain) Amyloidosis

PURPOSE To assess the efficacy and tolerability of bortezomib with or without dexamethasone and to define prognostic factors for patients with primary systemic light chain (AL) amyloidosis treated with bortezomib or both. PATIENTS AND METHODS Ninety-four patients from three centers were analyzed: 19% received the combination as first-line treatment, 81% had a median of two previous therapies, and 69% had refractory disease, while most patients had symptomatic heart involvement or elevated serum N-terminal pro-brain natriuretic peptide (NT-proBNP). Results A hematologic response was achieved in 71% within a median of 52 days, including 25% complete responses (CRs). Previously untreated patients had a 47% CR rate. Age 65 years or younger (P = .043) and twice weekly administration of bortezomib (P = .041) were associated with higher response rates. A cardiac response was documented in 29% of patients, in most as sustained improvement of functional class and less often as a decrease in wall thickness. Hematologic responses were associated with a cardiac response and NT-proBNP reduction. After a median follow-up of 12 months, 29% of patients had organ progression and 27% had hematologic progression. Median survival has not been reached and the 1-year survival rate is 76%. Baseline NT-proBNP was independently associated with survival (P = .001), while in a landmark analysis, survival was associated with NT-proBNP reduction of > or = 30% (P = .006) and achievement of hematologic response (P = .001). Toxicity was manageable and mostly consisted of neuropathy, orthostasis, peripheral edema, and constipation or diarrhea. CONCLUSION Bortezomib with or without dexamethasone is active in AL amyloidosis and induces rapid responses and high rates of hematologic and organ responses. Serial measurement of cardiac biomarkers is a powerful predictor of outcome.

Soluble ST2 Monitoring Provides Additional Risk Stratification for Outpatients With Decompensated Heart Failure

The novel biomarker ST2 provides diagnostic information in a variety of clinical settings. The objective was to determine whether measurement of the soluble ST2 (sST2) concentration improves risk stratification in outpatients with decompensated heart failure (HF). The concentrations of sST2 and N-terminal probrain natriuretic peptide (NT-proBNP) and a heart failure severity score (HFSS), based on Framingham criteria, were determined at baseline and 2 weeks later in 48 outpatients with decompensated hf. The ratio of the value of each variable at week 2 relative to baseline was determined. Patients were followed for 1 year and cardiac events (i.e. death, HF admission and heart transplantation) were recorded. By 1 year, 56% of patients had experienced a cardiac event. The sST2 ratio was significantly lower in patients who did not have a cardiac event (0.6 ± 0.39 vs. 1.39 ± 0.92; P< .001). After multivariable adjustment, the sST2 ratio remained an independent predictor of risk (odds ratio=1.054; 95% confidence interval, 1.01-1.09; P=.017). The optimum cut-point for the sST2 ratio determined by receiver operating curve [ROC] analysis was 0.75; this accounted for 25% of the change in sST2 by week 2. Among patients with an sST2 ratio >0.75 and a baseline NT-proBNP level >1000 ng/L, 72% had a cardiac event (P=.018), while no events occurred in patients with marker values below these reference levels. Determination of the sST2 concentration in serial samples provided additional risk stratification in outpatients with decompensated HF. Repeated measurement of sST2 may aid clinical decision-making.

N-terminal pro–brain natriuretic peptide and exercise capacity in chronic heart failure: Data from the Heart Failure and a Controlled Trial Investigating Outcomes of Exercise Training (HF-ACTION) study

To examine the relationship between N-terminal pro-brain natriuretic peptide (NT-proBNP) and exercise capacity in a large contemporary cohort of patients with chronic heart failure. Natriuretic peptides such as NT-proBNP are important biomarkers in heart failure. The relationship between NT-proBNP and exercise capacity has not been well studied. We analyzed the relationship between baseline NT-proBNP and peak oxygen uptake (peak VO(2)) or distance in the 6-minute walk test in 1383 subjects enrolled in the HF-ACTION study. Linear regression models were used to analyze the relationship between NT-proBNP and peak Vo(2) or distance in the 6-minute walk test in the context of other clinical variables. Receiver operator curve analysis was used to evaluate the ability of NT-proBNP to accurately predict a peak VO(2) <12 mL/kg per minute. NT-proBNP was the most powerful predictor of peak VO(2) (partial R(2) = 0.13, P < .0001) of 35 candidate variables. Although NT-proBNP was also a predictor of distance in the 6-minute walk test, this relationship was weaker than that for peak VO(2) (partial R(2) = 0.02, P < .0001). For both peak VO(2) and distance in the 6-minute walk test, much of the variability in exercise capacity remained unexplained by the variables tested. Receiver operator curve analysis suggested NT-proBNP had moderate ability to identify patients with peak VO(2) <12 mL/kg per minute (c-index, 0.69). In this analysis of baseline data from HF-ACTION, NT-proBNP was the strongest predictor of peak VO(2) and a significant predictor of distance in the 6-minute walk test. Despite these associations, NT-proBNP demonstrated only modest performance in identifying patients with a low peak VO(2) who might be considered for cardiac transplantation. These data suggest that, although hemodynamic factors are important determinants of exercise capacity, much of the variability in exercise performance in heart failure remains unexplained by traditional clinical and demographic variables.

Predisposing Factors and Consequences of Elevated Biomarker Levels in Long-Distance Runners Aged ≥55 Years

Cardiac biomarkers play an important role in the diagnosis of cardiovascular disease. Elevated levels can be seen in the context of strenuous exercise. We studied this phenomenon in senior endurance runners. We included 185 participants (61.1 +/- 5 years; 29% women) at a 30-km cross-country race who were self-reportedly in excellent health. Before and after the race, the creatinine, N-terminal pro-brain natriuretic peptide (NT-proBNP), and troponin T were analyzed, and participation in the number of previous races and the race duration were recorded. NT-proBNP increased from 53 ng/L (interquartile range 31 to 89) to 121 ng/L (interquartile range 79 to 184) and troponin T from undetectable to 0.01 microg/L (interquartile range 0.01 to 0.04). The independent predictors of a large NT-proBNP increase were (1) greater levels present at baseline, (2) a greater increase in creatinine (both p <0.001), (3) older age (p = 0.01), and (4) a longer race duration (p <0.05). Troponin T elevation was independently predicted by (1) older age (p = 0.01), (2) a greater increase in creatinine, and (3) participation in fewer previous races (both p <0.05). Of the 15 runners with an elevated (>194 ng/L) baseline NT-proBNP level (8.1% of 185), 4 were found to have serious cardiovascular disease (2.2% of whole sample). Of these 4 patients, 1 died from sudden cardiac death within months after the race. In conclusion, biomarker elevation occurs commonly in senior runners. A high baseline NT-proBNP is predictive of a large release during exercise, suggesting that the factors that control the at rest levels also determine its release with exertion. Troponin T elevation was seen in less-experienced participants. A small group of very ill runners were identified by NT-proBNP analysis.