Prohormone Brain Natriuretic Peptide Levels Research Articles

Do Predictors of Incomplete Kawasaki Disease Exist for Infants?

Kawasaki disease (KD), an acute febrile vasculitis, is the most common cause of acquired heart disease in infants and young children. However, the diagnosis of infantile KD can be difficult or delayed due to vague clinical manifestations. This current study aimed to assess the clinical characteristics and cardiac complications of infantile KD. The study retrospectively reviewed the data of 242 patients with KD. The clinical, laboratory, and echocardiographic data between infants and older children were analyzed. The patients were divided into two groups: infants 12 months old or younger and children older than 12 months. The rate of incomplete KD was much more frequent in infants. During all phases, prohormone brain natriuretic peptide (Pro-BNP) levels were higher in infants, as was thrombocytosis. The coronary artery z-score was higher in infants at all phases of KD. On tissue Doppler imaging, the E/E' ratio (ratio of transmitral Doppler early filling velocity to tissue Doppler early diastolic mitral annular velocity) was higher at the septal and lateral annulus in infants. Infant patients with KD are at increased risk for the development of coronary abnormalities and diastolic dysfunction. Higher levels of Pro-BNP and thrombocytosis with diastolic echo parameters of a higher E/E' ratio can help to identify incomplete KD in infants.

Different Treatment Interventions Affect Plasma NT-ProBNP Levels and Early Exercise Tolerance in Patients with Acute ST-Segment Elevation Myocardial Infarction

Objective: The aim of this study was to investigate the effect of different treatment interventions on plasma N–terminal fragment of the prohormone brain natriuretic peptide (NT–proBNP) levels and early exercise tolerance in patients with acute ST–segment elevation myocardial infarction. Methods: 146 consecutive patients with ST–segment elevation myocardial infarction who received emergency percutaneous coronary intervention (PCI) (n = 55), elective PCI (n = 47), or drug treatment (n = 44) were included. Plasma NT–proBNP levels and left ventricular ejection fractions (LVEFs) were measured before the treatment intervention and at 1 week and 1 month afterward. An exercise stress test was performed 1 month after the intervention, and the occurrences of major adverse cardiac events (MACE) were recorded at the 1-month follow–up. Results: Compared with the elective PCI and drug treatment groups, at 1 week and 1 month after the intervention, the emergency PCI group's plasma NT–proBNP levels were significantly lower, and the group's LVEFs were significantly higher (all P < 0.05). There was a significantly negative correlation between plasma NT–proBNP levels and LVEFs in each group (all P < 0.05). The positive exercise stress testing rates were 13.0%, 32.6%, and 38.6% in the emergency PCI, elective PCI, and drug treatment groups, respectively (P < 0.05). The occurrences of MACE in the emergency PCI, elective PCI, and drug treatment groups were 34.5%, 59.5%, and 65.9%, respectively (P < 0.05). Conclusion: Emergency PCI resulted in lower plasma NT–proBNP levels, lower MACE incidence, higher LVEFs, and better early exercise tolerance compared with elective PCI or drug treatment, indicating that lower plasma NT–proBNP levels predicted a better prognosis.

Exercise training improves exercise capacity in adult patients with a systemic right ventricle: a randomized clinical trial

To assess whether exercise training in adult patients with a systemic right ventricle (RV) improves exercise capacity and quality of life and lowers serum N-terminal prohormone brain natriuretic peptide (NT-proBNP) levels. Multi-centre parallel randomized controlled trial. Patients with a systemic RV due to congenitally or surgically corrected transposition of the great arteries. Fifty-four adult patients with a systemic RV, were randomized using unmarked opaque envelopes to an intervention group (n = 28) with three training sessions per week for 10 consecutive weeks, and a control group (n = 26). Randomization was stratified by participating centre. At baseline, and follow-up, we determined maximal exercise capacity (V'O(2peak)), serum NT-proBNP levels, and quality of life by means of the SF-36, and the TAAQOL Congenital Heart Disease questionnaires. The final analysis was performed by linear regression, taking into account the stratified randomization. Forty-six patients were analysed (male 50%, age 32 ± 11 years, intervention group n = 24, control group n = 22). Analysis at 10 weeks showed a significant difference in V'O(2peak) (3.4 mL/kg/min, 95% CI: 0.2 to 6.7; P = 0.04) and resting systolic blood pressure (-7.6 mmHg, 95% CI: -14.0 to -1.3; P = 0.03) in favour of the exercise group. No significant changes were found in serum NT-proBNP levels or quality of life in the intervention group or in the control group nor between groups. None of the patients in the intervention group had to discontinue the training programme due to adverse events. In adult patients with a systemic RV exercise training improve exercise capacity. We recommend to revise restrictive guidelines, and to encourage patients to become physically active. ( The study was registered at http://trialregister.nl. Identifier: NTR1909.).

Calcium Upregulation by Percutaneous Administration of Gene Therapy in Cardiac Disease (CUPID)

Background— Adeno-associated virus type 1/sarcoplasmic reticulum Ca 2+ -ATPase was assessed in a randomized, double-blind, placebo-controlled, phase 2 study in patients with advanced heart failure. Methods and Results— Thirty-nine patients received intracoronary adeno-associated virus type 1/sarcoplasmic reticulum Ca 2+ -ATPase or placebo. Seven efficacy parameters were assessed in 4 domains: symptoms (New York Heart Association class, Minnesota Living With Heart Failure Questionnaire), functional status (6-minute walk test, peak maximum oxygen consumption), biomarker (N-terminal prohormone brain natriuretic peptide), and left ventricular function/remodeling (left ventricular ejection fraction, left ventricular end-systolic volume), plus clinical outcomes. The primary end point success criteria were prospectively defined as achieving efficacy at 6 months in the group-level (concordant improvement in 7 efficacy parameters and no clinically significant worsening in any parameter), individual-level (total score for predefined clinically meaningful changes in 7 efficacy parameters), or outcome end points (cardiovascular hospitalizations and time to terminal events). Efficacy in 1 analysis had to be associated with at least a positive trend in the other 2 analyses. This combination of requirements resulted in a probability of success by chance alone of 2.7%. The high-dose group versus placebo met the prespecified criteria for success at the group-level, individual-level, and outcome analyses (cardiovascular hospitalizations) at 6 months (confirmed at 12 months) and demonstrated improvement or stabilization in New York Heart Association class, Minnesota Living With Heart Failure Questionnaire, 6-minute walk test, peak maximum oxygen consumption, N-terminal prohormone brain natriuretic peptide levels, and left ventricular end-systolic volume. Significant increases in time to clinical events and decreased frequency of cardiovascular events were observed at 12 months (hazard ratio=0.12; P =0.003), and mean duration of cardiovascular hospitalizations over 12 months was substantially decreased (0.4 versus 4.5 days; P =0.05) on high-dose treatment versus placebo. There were no untoward safety findings. Conclusions— The Calcium Upregulation by Percutaneous Administration of Gene Therapy in Cardiac Disease (CUPID) study demonstrated safety and suggested benefit of adeno-associated virus type 1/sarcoplasmic reticulum Ca 2+ -ATPase in advanced heart failure, supporting larger confirmatory trials. Clinical Trial Registration— http://www.clinicaltrials.gov . Unique identifier: NCT00454818.

Parenteral administration of recombinant human neuregulin‐1 to patients with stable chronic heart failure produces favourable acute and chronic haemodynamic responses

Neuregulin-1 (NRG-1) plays a critical role in the adaptation of the heart to injury, inhibiting apoptosis and inducing cardiomyocyte proliferation. We have shown previously that rhNRG-1 improves cardiac function and survival in animal models of cardiomyopathy. Here we report the first human study aimed at exploring the acute and chronic haemodynamic responses to recombinant human NRG-1 (beta(2a) isoform; rhNRG-1) in patients with stable chronic heart failure (CHF). Fifteen patients (age, 60 ± 2; NYHA II:III, 9:6; left ventricular ejection fraction (LVEF) <40%) on optimal medical therapy for CHF, received a rhNRG-1 infusion daily for 11 days. Acute and chronic haemodynamic, structural and biochemical effects were determined by serial right heart catheterization, cardiac magnetic resonance (CMR), echocardiography and measurement of neurohumoral indices. Acutely, cardiac output increased by 30% during a 6 h rhNRG-1 infusion (P < 0.01). Pulmonary artery wedge pressure and systemic vascular resistance decreased 30 and 20%, respectively, at 2 h (P < 0.01). A 47% reduction in serum noradrenaline, a 55% reduction in serum aldosterone and a 3.6-fold increase in N-terminal prohormone brain natriuretic peptide levels were concurrently observed (P < 0.001). These acute haemodynamic effects were sustained, as demonstrated by the 12% increase in LVEF from 32.2 ± 2.0% (baseline) to 36.1 ± 2.3% (mean ± SE, P < 0.001) at 12 weeks. The therapy was well tolerated. rhNRG-1 appears to produce favourable acute and chronic haemodynamic effects in patients with stable CHF on optimal medical therapy. Randomized controlled trials of rhNRG-1 in cardiac disease are thus warranted. Clinical Trial Registration Information The trial was registered with the Australian New Zealand Clinical Trials Registry, anzctr.org.au Identifier: ACTRN12607000330448.

The effects of adding torasemide to standard therapy on peak oxygen consumption, natriuretic peptides, and quality of life in patients with compensated left ventricular systolic dysfunction

Diuretics, when used to treat congestion in patients with chronic heart failure, improve symptoms and, perhaps, prognosis but little information is available to guide their use in patients with left ventricular systolic dysfunction (LVSD) who are not congested. Chronic diuretic therapy causes persistent and potentially harmful neuroendocrine activation. Alternatively, in patients in whom neuroendocrine activation is blocked with angiotensin-converting enzyme (ACE)-inhibitors and beta-blockers, diuretics may be beneficial by decreasing preload and afterload and preventing congestion. We aimed to assess the effect of the loop diuretic, torasemide on quality of life, and surrogate markers of prognosis when given to patients with LVSD who were not clinically congested and who were optimally treated with ACE-inhibitors (or angiotensin receptor antagonists) and beta-blockers. Thirty patients with stable LVSD who had no clinically detectable fluid overload were randomized to receive either torasemide 5 mg daily or placebo for 3 months (Phase A), and after a washout phase of 2 months, cross-over was performed for 3 months (Phase B). Diuretic therapy did not cause significant change in peak VO(2), mean N-terminal pro-hormone brain natriuretic peptide (NT-proBNP) levels, or measures of quality of life compared with placebo. Diuretic therapy did however lead to significant fall in systolic and diastolic blood pressures and increase in plasma renin levels compared with placebo. Diuretic therapy with torasemide is not superior to placebo in improving peak VO(2) or reducing NT-proBNP levels in patients with left ventricular dysfunction who are not clinically congested.

Clinical characteristics, and laboratory and echocardiographic findings in takotsubo cardiomyopathy presenting as cardiogenic shock

Purpose Although takotsubo cardiomyopathy (TTC) has been reported to have an excellent clinical recovery, there are few data regarding clinical, laboratory, and echocardiographic findings in TTC presenting as cardiogenic shock. We aimed to assess the differences in these parameters between TTC presenting with and without cardiogenic shock. Methods Fifty patients were enrolled from the TTC registry database and divided according to the presence of cardiogenic shock. Sixteen patients presented with cardiogenic shock as initial presentation (S group), and 34 did not (NS group). Results The S group had a higher prevalence of dyspnea (81% vs 38%, P = .005), pulmonary edema (69% vs 29%, P = .009), and significant reversible mitral regurgitation (44% vs 15%, P = .025) than the NS group. In addition, the S group had significantly higher troponin-I (median, 8.2 vs 1.4 pg/mL; P = .043) and N-terminal prohormone brain natriuretic peptide levels (median, 8831 vs 2348 pg/mL; P = .046). During follow-up (median, 3.1 years), cardiac deaths associated with TTC itself and recurrences of TTC were not noted in both groups. Conclusions The S group has a higher prevalence of heart failure symptoms, significant reversible mitral regurgitation, and troponin-I and N-terminal prohormone brain natriuretic peptide levels. However, with meticulous therapeutic strategies, prognosis of this syndrome may be excellent irrespective of hemodynamic instability.

N-terminal prohormone brain natriuretic peptide-proBNP levels in ventricular arrhythmias in children.

Ventricular arrhythmias are the most common consequences of structural and functional heart diseases, but cases with no evident pathology are also observed. A parameter indicating asymptomatic circulatory failure could support decisions related to possible treatment of ventricular arrhythmias. The study objective was the evaluation of N-terminal prohormone brain natriuretic peptide (NT-proBNP) levels in children with ventricular arrhythmias and an attempt to determine if this parameter may be used for diagnosis and prognosis of ventricular arrhythmias. The study population was comprised of 36 children age 5 to 17.5 years old with idiopathic ventricular arrhythmias (Group B) graded mild or potentially malignant; 29 patients with mild ventricular arrhythmias were included into Group B1; and 7 patients with potentially malignant cases into Group B2. In all the patients, NT-proBNP assays were performed. The NT-proBNP levels in Groups B, B1, B2 and the control group (Group K) were as follows: 41.5 +/- 15.1 pg/mL, 35.5 +/- 18.5 pg/mL, 66.3 +/- 24.9 pg/mL and 31.5 +/- 15.1 pg/mL, respectively. Between the groups with and without arrhythmias (Group B vs Group K), no statistically significant differences in NT-proBNP levels were found. However, markedly higher NT-proBNP levels were shown in the children with potentially malignant arrhythmias (Group B2) compared to the patients with mild arrhythmias (B1) and the control group (Group K). The level of NT-proBNP increases with the severity of ventricular arrhythmia. NT-proBNP assays can be helpful for diagnosing and grading the severity of ventricular arrhythmias.

Plasma Urocortin 1 in Human Heart Failure

The urocortins are emerging as potentially important contributors to neurohumoral regulation of the circulation with recent reports attributing a powerful array of hemodynamic, renal, and neurohumoral effects to the urocortins in cardiac failure. These peptides also seem to have cardioprotective effects in the setting of ischemia-reperfusion. Little is known concerning the plasma concentrations of the urocortins in health and disease. We have investigated plasma urocortin 1 as a potential diagnostic marker of heart failure and documented its relationships to symptoms, measures of cardiac function, and concurrent levels of other circulating neurohormones. In 299 patients with recent onset dyspnea or peripheral edema presenting to primary care, plasma urocortin 1 and other vasoactive hormones were assayed, and echocardiography was performed. Heart failure was present in 74 patients (25%) according to predefined diagnostic criteria. Urocortin 1 levels were increased in patients with heart failure and were related to functional class, clinical signs of heart failure, echocardiographic indicators of left ventricular dimensions and function, plasma creatinine, and concurrent circulating levels of plasma natriuretic peptides, adrenomedullin, and endothelin 1. Plasma urocortin 1 is elevated in heart failure (in proportion to the degree of cardiac dysfunction) in concert with the generalized neurohormonal activation seen in this condition. Urocortin levels predict heart failure independent of age, history of previous myocardial infarction, diabetes, hypertension, fractional shortening, and N-terminal prohormone brain natriuretic peptide levels.

Diazoxide protects myocardial mitochondria, metabolism, and function during cardiac surgery: A double-blind randomized feasibility study of diazoxide-supplemented cardioplegia

The study was designed to assess whether diazoxide-mediated cardioprotection might be used in human subjects during cardiac surgery. Forty patients undergoing coronary artery bypass grafting were randomized to receive intermittent warm blood antegrade cardioplegia supplemented with either diazoxide (100 micromol/L) or placebo (n = 20 in each group). Mitochondria were assessed before and after ischemia and reperfusion in myocardial biopsy specimens. Myocardial oxygen and glucose and lactic acid extraction ratios were measured before ischemia and in the first 20 minutes of reperfusion. Hemodynamic data were collected, and troponin I, creatine kinase-MB, and N-terminal prohormone brain natriuretic peptide levels were measured. All outcomes were analyzed by using mixed-effects modeling for repeated measures. No deaths, strokes, or infarcts were observed. Patients received, on average, 36.2 +/- 1.2 mg of diazoxide and 37.3 +/- 1.9 mg of placebo (P = .6). Diazoxide added to cardioplegia prevented mitochondrial swelling (8899 +/- 474 vs 9273 +/- 688 pixels before and after the procedure, respectively; P = .6) compared with that seen in the placebo group (8474 +/- 163 vs 11,357 +/- 759 pixels, P = .004). No oxygen debt was observed in the diazoxide group. Glucose consumption and lactic acid production returned to preischemic values faster in the diazoxide group. The following hemodynamic parameters differed between the diazoxide and placebo groups, respectively, in the postoperative period: cardiac index, 3.0 +/- 0.09 versus 2.6 +/- 0.09 L . min(-1) . m(-2) (P = .002); left cardiac work index, 2.81 +/- 0.07 versus 2.31 +/- 0.07 kg/m(2) (P < .001); oxygen delivery index, 420 +/- 14 versus 377 +/- 13 mL . min(-1) . m(-2) (P = .03); and oxygen extraction ratio, 29.3% +/- 1.1% versus 32.6% +/- 1.1% (P = .02). Postoperative myocardial enzyme levels did not differ, but N-terminal prohormone brain natriuretic peptide levels were lower in the diazoxide group (120 +/- 27 vs 192 +/- 29 pg/mL, P = .04). Supplementing blood cardioplegia with diazoxide is safe and improves myocardial protection during cardiac surgery, possibly through its influence on the mitochondria.

Atorvastatin Therapy Is Associated with Reduced Levels of N‐terminal Prohormone Brain Natriuretic Peptide and Improved Cardiac Function in Patients with Heart Failure

Statins have been suggested to improve cardiac function, but the evidence underlying beneficial effects of statins in heart failure (HF) is insufficient. We analyzed plasma N-terminal prohormone brain natriuretic peptide (NT-proBNP) levels and cardiac function in patients with HF of various etiologies, and who were treated with or without statins. Statin treatment is associated with improved cardiac function in HF. The study cohort consisted of 139 consecutive male patients receiving atorvastatin (n = 44), simvastatin (n = 29), pravastatin (n = 19), or no statin (n = 47). The NT-proBNP levels were measured using electroluminescence immunoassay. Left ventricular end-diastolic diameter (LVEDD), fractional shortening (FS), and ejection fraction (EF) were determined by echocardiography. Patients receiving atorvastatin presented with reduced NT-proBNP levels (1,552 +/- 3,416 versus 3,771 +/- 6,763 pg/mL; p < 0.01), and improved values of LVEDD (65.2 +/- 8.9 versus 70.7 +/- 10.9 mm; p < 0.05) and EF (33.2 +/- 12.6 versus 28.2 +/- 9.6%; p < 0.05). By contrast, plasma NT-proBNP and cardiac parameters in patients treated with statins other than atorvastatin did not significantly differ from control. Atorvastatin treatment was equally effective in patients with ischemic and nonischemic HF. Atorvastatin treatment is associated with improved cardiac function in HF, and may represent an additional option for patients with this disease.

Relation of Physical Activity, Cardiac Function, Exercise Capacity, and Quality of Life in Patients With a Systemic Right Ventricle

Exercise is recommended in patients with left ventricular failure. Although right ventricular failure is common in patients with a systemic right ventricle (RV), no data are available on the effect of physical activity in these patients. The aim of this study was to evaluate the relation of physical activity and cardiac function, exercise capacity, and quality of life in patients with a systemic RV. Forty-seven patients (64% men, mean age 35 years, range 21 to 69) with a systemic RV (31 with an atrially switched transposition of the great arteries and 16 with a congenitally corrected transposition of the great arteries) were included. Cardiac function was assessed by cardiovascular magnetic resonance or computed tomography, exercise tests, and serum N-terminal prohormone brain natriuretic peptide (NT-pro-BNP) levels. Habitual physical activity was assessed using the Short Questionnaire to Assess Health-Enhancing Physical Activity (SQUASH) and quality of life using the Medical Outcomes Study Short Form 36-Item Health Survey. Mean systemic right ventricular ejection fraction was impaired (36.8 +/- 7.8%), as was maximal exercise capacity (78.5 +/- 23.9% of predicted). NT-pro-BNP level was increased (median 269 ng/L, range 34 to 4,476). Mean SQUASH score was 6,808 +/- 3,241, indicating a decreased level of habitual physical activity. Although patients' scores on mental quality-of-life domains were comparable to the general population, scores on most physical quality-of-life domains were significantly lower. SQUASH scores were found to be a significant predictor for exercise capacity (p <0.01) and physical quality of life (p <0.001). However, we found no relation between SQUASH scores and right ventricular ejection fraction or NT-pro-BNP. In conclusion, physical activity in patients with a systemic RV is positively associated with exercise capacity and quality of life, irrespective of cardiac performance.