Cardiac B-type Natriuretic Peptide Research Articles

Evaluation and comparison of biomarkers in decompensated heart failure in a tertiary care center

Objective. This research delves into decompensated heart failure (DHF), aiming to comprehensively evaluate and compare biomarkers within a tertiary care center. Recognizing DHF's clinical challenges and high morbidity and mortality rates, the study seeks to enhance understanding and shed light on underlying mechanisms, particularly the role of biomarkers. Methodology. Utilizing a retrospective cohort design, the study spans electronic health records from 2010 to 2022. Ethical considerations, including IRB approval and informed consent, are paramount. Biomarkers such as cardiac troponins, B-type natriuretic peptide (BNP), and C-reactive protein (CRP) undergo rigorous assessment via advanced laboratory techniques. Statistical analyses, encompassing t-tests and ANOVA, provide a robust foundation for discerning patterns and correlations. This study includes 200 patients diagnosed with DHF (experimental group) and 200 control patients without DHF (control group). Results. Baseline characteristics highlight subtle differences between DHF patients (experimental group) and controls. Biomarker analysis reveals statistically significant elevations in cardiac troponins, BNP, and CRP in DHF cases compared to controls. The mean levels in survivors and non-survivors underscore the potential prognostic value of these biomarkers. ANOVA results suggest no significant differences in age, gender distribution, and BMI between the groups, reinforcing the robustness of the findings. Conclusion. This study significantly contributes to DHF management insights, emphasizing the diagnostic and prognostic potential of biomarkers. The observed disparities in biomarker levels, coupled with consistent baseline characteristics, provide valuable insights for clinical considerations and future research in DHF management. The nuanced interpretation of results not only expands knowledge of DHF but also offers actionable insights for clinicians dealing with this complex condition. The study's comprehensive approach, combining clinical, demographic, and biomarker data, lays a strong foundation for future investigations and interventions in DHF.

Morphometric, Developmental, and Anti-Inflammatory Effects of Transamniotic Stem Cell Therapy (TRASCET) on the Fetal Heart and Lungs in a Model of Intrauterine Growth Restriction.

Transamniotic stem cell therapy (TRASCET) with mesenchymal stem cells (MSCs) can attenuate placental inflammation and minimize intrauterine growth restriction (IUGR). We sought to determine whether MSC-based TRASCET could mitigate fetal cardiopulmonary effects of IUGR. Pregnant Sprague-Dawley dams were exposed to alternating 12-h hypoxia (10.5% O2) cycles in the last fourth of gestation. Their fetuses (n = 155) were divided into 4 groups. One group remained untreated (n = 42), while three groups received volume-matched intra-amniotic injections of either saline (sham; n = 34), or of syngeneic amniotic fluid-derived MSCs, either in their native state (TRASCET; n = 36) or "primed" by exposure to interferon-gamma and interleukin-1beta before administration in vivo (TRASCET-primed; n = 43). Normal fetuses served as additional controls (n = 30). Multiple morphometric and biochemical analyses were performed at term for select markers of cardiopulmonary development and inflammation previously shown to be affected by IUGR. Among survivors (75%; 117/155), fetal heart-to-body weight ratio was increased in both the sham and untreated groups (P < 0.001 for both) but normalized in the TRASCET and TRASCET-primed groups (P = 0.275, 0.069, respectively). Cardiac b-type natriuretic peptide levels were increased in all hypoxia groups compared with normal (P < 0.001), but significantly decreased from sham and untreated in both TRASCET groups (P < 0.0001-0.005). Heart tumor necrosis factor-alpha levels were significantly elevated in sham and TRASCET groups (P = 0.009, 0.002), but normalized in the untreated and TRASCET-primed groups (P = 0.256, 0.456). Lung transforming growth factor-beta levels were significantly increased in both sham and untreated groups (P < 0.001, 0.003), but normalized in both TRASCET groups (P = 0.567, 0.303). Similarly, lung endothelin-1 levels were elevated in sham and untreated groups (P < 0.001 for both), but normalized in both TRASCET groups (P = 0.367, 0.928). We conclude that TRASCET with MSCs decreases markers of fetal cardiac strain, insufficiency, and inflammation, as well as of pulmonary fibrosis and hypertension in the rodent model of IUGR.

Effects of phosphodiesterase V inhibition alone and in combination with BNP on cardiovascular and renal response to volume load in human preclinical diastolic dysfunction.

Preclinical diastolic dysfunction (PDD) results in impaired cardiorenal response to volume load (VL) which may contribute to the progression to clinical heart failure with preserved ejection fraction (HFpEF). The objective was to evaluate if phosphodiesterase V inhibition (PDEVI) alone or combination PDEVI plus B‐type natriuretic peptide (BNP) administration will correct the impaired cardiorenal response to VL in PDD. A randomized double‐blinded placebo‐controlled cross‐over study was conducted in 20 subjects with PDD, defined as left ventricular ejection fraction (LVEF) >50% with moderate or severe diastolic dysfunction by Doppler echocardiography and without HF diagnosis or symptoms. Effects of PDEVI with oral tadalafil alone and tadalafil plus subcutaneous (SC) BNP, administered prior to acute volume loading, were assessed. Tadalafil alone did not result in improvement in cardiac response to VL, as measured by LVEF, LV end diastolic volume, left atrial volume (LAV), or right ventricular systolic pressure (RVSP). Tadalafil plus SC BNP resulted in improved cardiac response to VL, with increased LVEF (4.1 vs. 1.8%, p = 0.08) and heart rate (4.3 vs. 1.6 bpm, p = 0.08), and reductions in both LAV (−4.3 ± 10.4 vs. 2.8 ± 6.6 ml, p = 0.03) and RVSP (−4.0 ± 3.0 vs. 2.1 ± 6.0 mmHg, p < 0.01) versus tadalafil alone. Plasma and urinary cyclic guanosine monophosphate (cGMP) excretion levels were higher (11.3 ± 12.3 vs. 1.7 ± 3.8 pmol/ml, 1851.0 ± 1386.4 vs. 173.4 ± 517.9 pmol/min, p < 0.01) with tadalafil plus SC BNP versus tadalafil alone. There was no improvement in renal response as measured by GFR, renal plasma flow, sodium excretion, and urine flow with tadalafil plus SC BNP compared to tadalafil alone. In subjects with PDD, tadalafil alone resulted in no improvement in cardiac adaptation, while tadalafil and SC BNP resulted in enhanced cardiac adaptation to VL.Trial RegistrationClinicalTrials.gov NCT01544998.

Catheter ablation for non-paroxysmal atrial fibrillation accompanied by heart failure with preserved ejection fraction: feasibility and benefits in functions and B-type natriuretic peptide.

We aimed to examine the benefits of catheter ablation in patients with non-paroxysmal atrial fibrillation (AF) accompanied by heart failure (HF) with preserved ejection fraction (HFpEF), in comparison with the benefits in patients with AF accompanied by HF with reduced ejection fraction (HFrEF) or patients with no HF. From 1173 consecutive patients undergoing catheter ablation, 502 with non-paroxysmal AF were divided into three groups: no history of HF [plasma B-type natriuretic peptide (BNP) <100 pg/mL and no HF hospitalization; n = 125], HFpEF [left ventricular (LV) EF ≥50%; n = 293], and HF with midrange EF (HFmrEF) + HFrEF (LVEF <50%; n = 84) groups. The endpoints were AF recurrence at 1 year, changes in symptomatic and image-based functional status, and changes in BNP levels from baseline to 1 year. In the HFpEF group, AF recurred in 48 patients (16.4%) and 278 patients (94.8%) had sinus rhythm at 1 year; these values were comparable with those in the other groups. Significant improvement was observed in the left atrial diameter, LVEF, and New York Heart Association functional class in the HFpEF and HFmrEF + HFrEF groups. The BNP level significantly decreased irrespective of the index rate control status, and freedom from AF recurrence was an independent predictor of HF remission, defined as BNP <100 pg/mL at 1 year, in the HFpEF group. Catheter ablation is highly feasible for restoring sinus rhythm in non-paroxysmal AF with coexisting HFpEF, thereby improving cardiac function and BNP levels. Catheter ablation for AF may be an optional management strategy.

Astaxanthin suppresses lipopolysaccharide‑induced myocardial injury by regulating MAPK and PI3K/AKT/mTOR/GSK3β signaling.

Cardiac dysfunction is a significant manifestation of sepsis and it is associated with the prognosis of the disease. Astaxanthin (ATX) has been discovered to serve a variety of pharmacological effects, including anti-inflammatory, antioxidant and antiapoptotic properties. The present study aimed to investigate the role and mechanisms of ATX in sepsis-induced myocardial injury. Male C57BL/6 mice were divided into three groups (15 mice per group): Control group, lipopolysaccharide (LPS) group and LPS + ATX group. The cardiac dysfunction model was induced through an intraperitoneal injection of LPS (10 mg/kg) and ATX (40 mg/kg) was administered to the LPS + ATX group by intraperitoneal injection 30 min following the administration of LPS. All animals were sacrificed after 24 h. Inflammatory cytokine levels in the serum were detected using ELISAs, and cardiac B-type natriuretic peptide (BNP) levels were analyzed using western blot analysis and reverse transcription-quantitative PCR. Furthermore, the extent of myocardial injury was evaluated using pathological analysis, and cardiomyocyte apoptosis was analyzed using a TUNEL assay, in addition to determining the expression levels of Bcl-2 and Bax. The expression levels of proteins involved in the mitogen activated protein kinase (MAPK) and PI3K/AKT signaling pathways were also analyzed using western blot analysis. ATX significantly suppressed the LPS-induced increased production of TNF-α and IL-6 and suppressed the protein expression levels of BNP, Bax and Bcl-2 to normal levels. ATX also prevented the histopathological changes to the myocardial tissue and reduced the extent of necrosis. Furthermore, the treatment with ATX suppressed the LPS-activated MAPK and PI3K/AKT signaling. ATX additionally exerted a protective effect on cardiac dysfunction caused by sepsis by inhibiting MAPK and PI3K/AKT signaling.

B-type natriuretic peptide is upregulated by c-Jun N-terminal kinase and contributes to septic hypotension.

B-type natriuretic peptide (BNP) is secreted by ventricular cardiomyocytes in response to various types of cardiac stress and has been used as a heart failure marker. In septic patients, increased BNP suggests poor prognosis; however, no causal link has been established. Among various effects, BNP decreases systemic vascular resistance and increases natriuresis that leads to lower blood pressure. We previously observed that JNK inhibition corrects cardiac dysfunction and suppresses cardiac BNP mRNA in endotoxemia. In this study, we investigated the transcriptional mechanism that regulates BNP expression and the involvement of plasma BNP in causing septic hypotension. Our in vitro and in vivo findings confirmed that activation of JNK signaling increases BNP expression in sepsis via direct binding of c-Jun in activating protein–1 (AP-1) regulatory elements of the Nppb promoter. Accordingly, genetic ablation of BNP, as well as treatment with a potentially novel neutralizing anti-BNP monoclonal antibody (19B3) or suppression of its expression via administration of JNK inhibitor SP600125 improved cardiac output, stabilized blood pressure, and improved survival in mice with polymicrobial sepsis. Therefore, inhibition of JNK signaling or BNP in sepsis appears to stabilize blood pressure and improve survival.

High-sensitivity troponin I and B-type natriuretic peptide biomarkers for prediction of cardiovascular events in patients with coronary artery disease with and without diabetes mellitus

BackgroundHigh-sensitivity troponin I (hs-Tnl) and B-type natriuretic peptide (BNP) are promising prognostic markers for coronary artery disease (CAD). This prospective cohort study investigated whether a combination of these cardiac biomarkers with conventional risk factors would add incremental value for the prediction of secondary major adverse cardiovascular events (MACEs) in patients with CAD, with and without type 2 diabetes mellitus (T2DM).MethodsBaseline plasma level of hs-Tnl and BNP was measured in 2275 Chinese patients with stable CAD. Patients were monitored for new-onset of MACE over a median of 51 months. Cox proportional hazard model and area under the receiver operating characteristic curve (AUC) were used to assess the association of cardiac biomarkers with MACE and their predictive values in relationship with or without T2DM.ResultsDuring the follow up period 402 (18%) patients experienced a new-onset MACE with hs-Tnl and BNP level significantly higher than in those without MACE. In multivariable analyses, patients with elevated hs-Tnl (hazard ratio, 1.75 [95% CI 1.41–2.17]; P < 0.001) and BNP (hazard ratio, 1.42 [95% CI 1.15–1.75]; P = 0.001) were significantly associated with an increased risk of MACE after adjustment for variables of a risk factor model of age, sex, T2DM and hypertension. The risk factor model had an AUC of 0.64 for MACE prediction. The AUC significantly increased to 0.68 by the addition of hs-Tnl to the risk factor model. Subgroup analyses showed that hs-Tnl and BNP remained significant predictors of MACE in both patients with and without T2DM in multivariable models with higher risk of MACE evident in those without T2DM. Among patients without T2DM, addition of each biomarker yielded greater predictive accuracy than in T2DM patients, with AUC further increased to 0.75 when a combination of hs-Tnl and BNP was added to the risk factor model (age, sex and hypertension).ConclusionsElevated hs-Tnl and BNP level are independent predictors of new-onset MACE in CAD patients, irrespective of diabetes status. Among CAD patients without T2DM, a combination of cardiac biomarkers hs-Tnl and BNP yield the greatest predictive value beyond conventional risk factors.

THE GROWTH HORMONE SECRETAGOGUE RECEPTOR, GHRELIN, AND BNP IN HUMAN HEART DISEASE WITH PRESERVED EJECTION FRACTION

Heart disease (HD) diagnosis is based on clinical features, imaging, and circulating biomarkers, notably B-type natriuretic peptide (BNP), the gold standard marker of heart failure. However, a cardiac-specific biomarker detecting contractile dysfunction at early stages is lacking. The growth hormone secretagogue receptor (GHSR) and its ligand ghrelin may be cardiac-specific biomarkers. We have characterized a fluorescent analog of ghrelin, Cy5-ghrelin (1-19) that detects changes in cardiac GHSR in situ in diabetic cardiomyopathy and heart failure. We are now using this tool to map changes in regional and cellular distribution of GHSR in HD. We obtained tissue from the left ventricle (LV) and right atrium (RA) from 10 cardiac surgery patients with preserved ejection fraction (pEF) and from 10 deceased donors with no history of HD. GHSR levels were measured by quantitative fluorescence microscopy using Cy5-ghrelin(1-19). Ghrelin and BNP were measured by immunofluorescence. High-resolution images were acquired using a Nikon A1R confocal microscope and fluorescence intensities were quantified using ImageJ FIJI's built-in algorithms (Shanbhag for GHSR or RenyiEntropy for ghrelin and BNP). Values of fluorescence intensities were compared based on individual algorithms and colocalization analysis was conducted with the NIS-Elements software. Data were analysed by t-test, one-way ANOVA, and Pearson correlation coefficient (PCC) with significance set at p < 0.05. There were significantly lower levels of GHSR in RA tissue samples from cardiac surgery patients (p=0.041) and no significant differences in ghrelin or BNP expression (Figure 1). There was strong colocalization of ghrelin and BNP in both healthy (PCC=0.935) and diseased (PCC=0.856) tissue samples. In healthy tissue, colocalization appeared as large, discretely defined punctate areas near the nucleus, whereas in the tissue from cardiac surgery patients, ghrelin and BNP signals were more diffuse and contained in smaller areas surrounding the nucleus (Figure 2, arrows). We have shown expression of GHSR, ghrelin and BNP in both healthy and diseased cardiac tissue with only GHSR significantly changing in HD. This may indicate GHSR expression is decreased in HD with pEF whereas BNP (elevated in end stage HF) and ghrelin are not changed. The strong correlation between ghrelin and BNP indicates that these markers may be stored in the same intracellular compartment near the nucleus where they are released upon cellular stress induced by HD. This is the first study showing colocalization between ghrelin and BNP in human cardiac tissue. We are currently stratifying these results based on sex, type of HD, and region of the heart.View Large Image Figure ViewerDownload Hi-res image Download (PPT)

Differential Regulation of ANP and BNP in Acute Decompensated Heart Failure: Deficiency of ANP

ObjectivesThis study investigated the differential regulation of circulating atrial natriuretic peptide (ANP) and B-type natriuretic peptide (BNP) in patients with acute decompensated heart failure (ADHF) and tested the hypothesis that a relative deficiency of ANP exists in a subgroup of patients with ADHF. BackgroundThe endocrine heart releases the cardiac hormones ANP and BNP, which play a key role in cardiovascular (CV), renal, and metabolic homeostasis. In heart failure (HF), both plasma ANP and BNP are increased as a compensatory homeostatic response to myocardial overload. MethodsANP and BNP concentrations were measured in a small group of patients with ADHF (n = 112). To support this study’s goal, a total of 129 healthy subjects were prospectively recruited to establish contemporary normal values for ANP and BNP. Plasma 3′,5′cyclic guanosine monophosphate (cGMP), ejection fraction (EF), and body mass index (BMI) were measured in these subjects. ResultsIn cases of ADHF, 74% of patients showed elevated ANP and BNP. Importantly, 26% of patients were characterized as having normal ANP (21% of this subgroup had normal ANP and elevated BNP). Cyclic GMP was lowest in the ADHF group with normal levels of ANP (p < 0.001), whereas BMI and EF were inversely related to ANP levels (p = 0.003). ConclusionsAmong a subgroup of patients hospitalized with ADHF, the presence of an ANP deficiency is consistent with a differential regulation of ANP and BNP and suggests the existence of a potentially compromised compensatory cardiac endocrine response. These findings have implications for the pathophysiology, diagnostics, and therapeutics of human HF.

Clinical Implications

Clinical Implications

\u03b2 Cell-specific deletion of guanylyl cyclase A, the receptor for atrial natriuretic peptide, accelerates obesity-induced glucose intolerance in mice

BackgroundThe cardiac hormones atrial (ANP) and B-type natriuretic peptides (BNP) moderate arterial blood pressure and improve energy metabolism as well as insulin sensitivity via their shared cGMP-producing guanylyl cyclase-A (GC-A) receptor. Obesity is associated with impaired NP/GC-A/cGMP signaling, which possibly contributes to the development of type 2 diabetes and its cardiometabolic complications. In vitro, synthetic ANP, via GC-A, stimulates glucose-dependent insulin release from cultured pancreatic islets and β-cell proliferation. However, the relevance for systemic glucose homeostasis in vivo is not known. To dissect whether the endogenous cardiac hormones modulate the secretory function and/or proliferation of β-cells under (patho)physiological conditions in vivo, here we generated a novel genetic mouse model with selective disruption of the GC-A receptor in β-cells.MethodsMice with a floxed GC-A gene were bred to Rip-CreTG mice, thereby deleting GC-A selectively in β-cells (β GC-A KO). Weight gain, glucose tolerance, insulin sensitivity, and glucose-stimulated insulin secretion were monitored in normal diet (ND)- and high-fat diet (HFD)-fed mice. β-cell size and number were measured by immunofluorescence-based islet morphometry.ResultsIn vitro, the insulinotropic and proliferative actions of ANP were abolished in islets isolated from β GC-A KO mice. Concordantly, in vivo, infusion of BNP mildly enhanced baseline plasma insulin levels and glucose-induced insulin secretion in control mice. This effect of exogenous BNP was abolished in β GC-A KO mice, corroborating the efficient inactivation of the GC-A receptor in β-cells. Despite this under physiological, ND conditions, fasted and fed insulin levels, glucose-induced insulin secretion, glucose tolerance and β-cell morphology were similar in β GC-A KO mice and control littermates. However, HFD-fed β GC-A KO animals had accelerated glucose intolerance and diminished adaptative β-cell proliferation.ConclusionsOur studies of β GC-A KO mice demonstrate that the cardiac hormones ANP and BNP do not modulate β-cell’s growth and secretory functions under physiological, normal dietary conditions. However, endogenous NP/GC-A signaling improves the initial adaptative response of β-cells to HFD-induced obesity. Impaired β-cell NP/GC-A signaling in obese individuals might contribute to the development of type 2 diabetes.

Multiplexed electrochemical detection of three cardiac biomarkers cTnI, cTnT and BNP using nanostructured ZnO-sensing platform.

Development of a label-free multiplexed point-of-care diagnostic device for a panel of cardiac biomarkers - cardiac troponin-T (cTnT), troponin-I (cTnI) and B-type natriuretic peptide (BNP). A nonfaradaic electrochemical immunoassay designed with anisotropic high surface area ZnO nanostructures grown using low-temperature hydrothermal methods was selectively immobilized with capture antibodies. Multiplexed detection in human serum using ZnO nanostructures based on complementary electrochemical measurement techniques - electrochemical impedance spectroscopy and Mott-Schottky. Linear signal response for detection of three biomarkers in human serum with dynamic range of 1pg/ml-100ng/ml and limit of detection at 1pg/ml and low signal response to background interferences was achieved. First demonstration of simultaneous detection of three cardiac biomarkers in clinically relevant range with sensor's analytical performance and linear response of detection showed potential utility in screening clinical samples for early diagnosis of acute myocardial infarction and chronic heart failure.

Inverse Association Between Myocardial B-Type Natriuretic Peptide Release and Functional Capacity in Healthy Humans

B-type natriuretic peptide (BNP) has been found to be inversely related to peak oxygen consumption (peak VO2) in various patient populations. However, in these studies, circulating plasma BNP, i.e. the net effect of release and elimination, rather than cardiac BNP release has been measured. We assessed the relationship between the transcardiac BNP gradient [ΔBNPCS-A, i.e. the difference between BNP in coronary sinus (BNPCS) and arterial (BNPA) plasma] and peak VO2 in healthy subjects with a view to better understanding the regulation of cardiac BNP release in humans. We studied 10 asymptomatic subjects (age 64±11 years, two females) with preserved left ventricular function (left ventricular ejection fraction 62±5%, averaged early diastolic mitral annular velocity 9±3cm/s) and low BNP (BNP in venous plasma [BNPV] <100ng/l). Subjects underwent measurement of BNPA and BNPCS for the calculation of ΔBNPCS-A, maximal cardiopulmonary exercise testing, echocardiography and resting and submaximal exercise right heart catheterisation. The median (range) BNPV, BNPA, BNPCS, and ΔBNPCS-A were 62 (14, 82), 60 (13, 79), 110 (25, 157), and 44 (1, 103) ng/l. The median peak VO2 during cardiopulmonary exercise testing was 21.5 (18, 54) ml/min/kg. There was an inverse correlation between higher ΔBNPCS-A and lower peak VO2 (r=-0.84; p=0.002) and oxygen pulse (r=-0.64, p=0.049). There was a trend towards an inverse correlation between ΔBNPCS-A and the exercise arteriovenous oxygen content difference (r=-0.58; p=0.08). In healthy humans, there is an inverse association between myocardial BNP release and peak VO2, which may be due to cardiac and non-cardiac mechanisms.

Cardiac hypertrophy-related pathways in obesity.

Obesity is often associated with the development of cardiac hypertrophy but the hypertrophy-related pathways in obesity remain unknown. The purpose of this study was to evaluate cardiac hypertrophy-related markers, atrial natriuretic peptide (ANP), B-type natriuretic peptide (BNP), tumor necrosis factor-alpha (TNFα) and hypertrophy-related pathways, interleukin (IL)-6-STAT3, IL-6-MEK5-ERK5 and calcineurin-nuclear factor of activated T-cells (NFAT)3 in the excised hearts from obese rats. Twelve obese Zucker rats were studied at 5-6 months of age and twelve age-matched lean Zucker rats served as the control group. The cardiac characteristics, myocardial architecture, ANP, BNP, TNFα levels, IL-6, STAT3, p-STAT3, MEK5, ERK-5, p-ERK-5, calcineurin and NFAT3 in the left ventricle from the rats were measured by heart weight index, echocardiography, vertical cross section, histological analysis, reverse transcription polymerase chain reaction and western blotting. Compared with the lean control, the whole heart weight, the left ventricule weight, the ratio of the whole heart weight to tibia length, echocardiographic interventricular septum, left ventricular posterior wall thickness, myocardial morphological changes and systolic blood pressure were found to increase in the obese rats. The protein levels of ANP, BNP, TNFα, IL-6, STAT3, p-STAT3, MEK-5, ERK-5, p-ERK 5, calcineurin and NFAT3 were also significantly increased in the hearts of the obese rats. The results showed that the hypertrophy-related markers, ANP, BNP and TNFα, the hypertrophy-related pathways IL-6-STAT3 and IL-6-MEK5-ERK5, and the calcineurin-NFAT3 hypertrophy-related pathways were more active in obese Zucker rats, which may provide possible hypertrophic mechanisms for developing cardiac hypertrophy and pathological changes in obesity.

Cardiac biomarkers and risk assessment in patients undergoing major non-cardiac surgery: time to revise the guidelines?

Although the perioperative event rate has declined over the past 30 years, as a consequence of the developments in anesthesiology and surgical techniques, perioperative cardiovascular complications are still a significant clinical problem. At the end of the last century, a pooled analysis of several large studies found a 30-day incidence of cardiac events of 2.5% in unselected patients aged >40 years. The identification of myocardial injury after non-cardiac surgery is a problematic and tough challenge, since up to 50% of cardiac deaths actually occur in patients with no history of overt heart disease. Recently, among novel sensitive and specific cardiovascular risk markers, the European Society of Cardiology and European Society of Anesthesiology guidelines for preoperative cardiac risk assessment have recommended that preoperative brain natriuretic peptide (BNP) or N-terminal fragment of proBNP (NT-proBNP) measurement should be considered in high-risk patients undergoing non-cardiac surgery. However, several recent studies and meta-analyses, published in the last 5 years, strongly support the use of both assays of cardiac B-type natriuretic peptides and troponins, for risk stratification in patients undergoing non-cardiac surgery, in order to improve operative and postoperative outcome. Indeed, an increase in specific cardiac biomarkers, as it is the case for natriuretic peptides and troponins, always indicates that the heart is under a stress condition or even actually injured, respectively. In conclusion, the authors suggest that future guidelines on cardiovascular risk evaluation in patients undergoing major surgical procedures should take into account the following evidence.

Cord blood B-type natriuretic peptide levels in placental insufficiency: correlation with fetal Doppler and pH at birth

ObjectiveTo examine the correlation of cardiac B-type natriuretic peptide (BNP) concentrations in umbilical cord blood at birth with fetal Doppler parameters and pH at birth. Study designProspective cross-sectional study with the following inclusion criteria: women with a singleton pregnancy, placental insufficiency characterized by increased pulsatility index (PI) of the umbilical artery (UA), intact membranes, and absence of fetal abnormalities. The exclusion criteria kept out cases of newborns with postnatal diagnosis of abnormality and cases in which the blood analysis was not performed. The Doppler parameters used were the UA PI, middle cerebral artery (MCA) PI, cerebroplacental ratio (CPR), and ductus venosus (DV) PI for veins (PIV), all converted into zeta scores. Blood samples were obtained from the umbilical cord immediately after delivery to measure the pH of the UA and the BNP. ResultsThirty-two pregnancies with placental insufficiency were included, 21 (65%) with positive diastolic flow and 11 (35%) with absent or reversed end diastolic flow in the UA. The concentration of BNP correlated significantly with the UA PI z-score (rho=0.43, P=0.016), the CPR z-score (rho=−0.35, P=0.048), the DV PIV z-score (rho=0.61, P<0.001), pH at birth (rho=−0.39, P=0.031), and gestational age (rho=−0.51, P=0.003). In the multiple regression analysis, antenatal parameters were included; the DV PIV z-score (P=0.008) was found to be an independent parameter correlating with BNP at birth. Correlation between BNP and the DV PIV z-score was borne out by the regression equation Log[BNP]=2.34+0.13*DV (F=18.8, P<0.001). Correlation between BNP and pH at birth was confirmed by the regression equation Log[BNP]=21.36–2.62*pH (F=7.69, P=0.01). ConclusionThe results suggest that fetal cardiac dysfunction identified by BNP concentrations at birth correlated independently with changes in DV PIV and correlated negatively with pH values at birth.

Levels of B-type natriuretic peptide in chronic heart failure patients with and without diabetes mellitus

The current study aimed to observe the value of B-type natriuretic peptide (BNP) in chronic heart failure (CHF) patients with and without diabetes mellitus (DM). The study consisted of 559 CHF patients, including 276 patients with coronary heart disease, 234 with hypertensive heart disease and 49 with dilated cardiomyopathy. The subjects were divided into non-DM and DM groups which included 384 and 175 patients, respectively. Their New York Heart Association (NYHA) cardiac function degree and BNP levels were detected following admission. Other blood parameters, including fasting blood glucose and serum creatinine, were also collected. Left ventricular ejection fraction (LVEF) and the average thickness of the left ventricular wall (LVW) were detected by echocardiography. The total score of the heart failure (HF)-related parameters was evaluated for each patient according to age, hypertension, LVEF, LVW and NYHA degree. Additionally, BNP-score relation curves were constructed. The levels of BNP were significantly higher in the DM group compared with the non-DM group (1143.73±94.0 vs. 884.34±57.0 ng/l, P<0.05). Positive BNP-score relation curves were obtained for the DM and non-DM groups, but the curve of the DM group was notably steeper. As the patients with DM have significantly higher BNP levels at a similar HF score, DM history and fasting blood glucose should be taken into consideration when evaluating the value of BNP in HF.

Cardiac production of B-type natriuretic peptide is inversely related to the plasma level of free fatty acids in obese individuals - possible involvement of the insulin resistance -

B-type natriuretic peptide (BNP) is produced by the heart and its plasma level is increased with the severity of left ventricular (LV) dysfunction/hypertrophy. The normal heart preferentially utilizes fatty acids as energy substrates. Plasma BNP levels are reported to be lower in obese individuals. We examined the relationship between BNP production and plasma free fatty acids (FFA), homeostasis model assessment of insulin resistance (HOMA-IR), and LV dysfunction/ hypertrophy. We examined the plasma BNP levels and FFA at the aortic root (AO) and coronary sinus (CS) as well as hemodynamic parameters in 62 patients (38 men and 24 women, 62.5±11.7 yrs) who underwent cardiac catheterization. Log BNP (AO) had a significant positive correlation with log BNP (CS-AO) (r=0.877, P<0.001). Log BNP(CS-AO) had a significant negative correlation with BMI (r=-0.558, P<0.001), waist circumference (WC) (r=-0.574, P<0.001), log FFA(AO) (r=-0.643, P<0.001), log triglyceride (r=-0.431, P<0.001), and log HOMA-IR (r=-0.463, P<0.001) and a significant positive correlation with left ventricular mass index (LVMI) (r=0.403, P=0.001). The multivariable regression analyses including log HOMA-IR, LVMI, and age as an independent variable revealed that HOMA-IR and LVMI were significant predictors of log BNP (CS-AO) or BNP production (P=0.001 and 0.004, respectively). We conclude that plasma BNP levels are determined primarily by cardiac production and that insulin resistance is a significant predictor of cardiac BNP production independent of LV hypertrophy in obese individuals.

Long-term cardiac pro-B-type natriuretic peptide gene delivery prevents the development of hypertensive heart disease in spontaneously hypertensive rats.

Diastolic dysfunction associated with high blood pressure (BP) leads to cardiac remodeling and fibrosis and progression to congestive heart failure. B-type natriuretic peptide (BNP) has BP-lowering, antifibrotic, and antihypertrophic properties, which makes BNP an attractive agent for attenuating the adverse cardiac remodeling associated with hypertension. In the current study, we tested the effects of sustained cardiac proBNP gene delivery on BP, cardiac function, and remodeling in spontaneously hypertensive rats (SHR). We used the myocardium-tropic adeno-associated virus serotype 9 (AAV9) vector to achieve continuously enhanced cardiac rat proBNP expression. In SHR, a single systemic administration of AAV9 vector allowed long-term cardiac BNP overexpression, resulting in reductions in systolic and diastolic BP for 9 months after injection. Left ventricular (LV) thickness, LV end-systolic dimensions, and LV mass were reduced, whereas ejection fraction was significantly increased, in BNP-treated compared with untreated SHR. Circumferential systolic strain and strain rate of the early phase of diastole were improved in BNP-treated compared with untreated SHR. Noncardiac overexpression of BNP via AAV2 vector was not associated with changes in BP and plasma BNP in SHR. Furthermore, normal Wistar rats injected with AAV9 proBNP vector showed significantly reduced heart weights 4 weeks after injection without BP reduction. AAV9 vector facilitates sustained cardiac proBNP overexpression and improves LV function in hypertensive heart disease. Long-term proBNP delivery improved both systolic and diastolic function. The effects on cardiac structure and function occurred independently of BP-lowering effects in normal Wistar rats.

B-type natriuretic peptide at the early stage of univentricular circulation reflects inadequate adaptation to volume overload

BackgroundRecent studies showed that children with univentricular heart have elevated plasma B-type natriuretic peptide (BNP) levels prior to bidirectional cavopulmonary anastomosis (BDCPA). However, it remains to be established whether BNP levels reflect the degree of hemodynamic overload and relate to long-term outcome in univentricular circulation. MethodsFifty one consecutive children with functionally univentricular heart prior to BDCPA were studied. All patients underwent cardiac catheterization and BNP measurement. Ventricular end-systolic wall stress (ESWS) and end-diastolic wall stress (EDWS) were calculated from cardiac catheterization data. ResultsMedian age was 1.1years and 34% were female. Median BNP concentration was 90.4pg/ml. Patients with high BNP (≥100pg/ml) had higher pulmonary to systemic flow ratio (p=0.014), a greater end-diastolic volume (p=0.009), more severe atrioventricular valve regurgitation (p=0.02) and lower ventricular mass to end-diastolic volume ratio (p=0.006). BNP levels strongly related to EDWS (r=0.75, p<0.0001) and ESWS (r=0.63, p<0.0001). During median follow-up period of 3.2years, 15 patients died and one underwent heart transplantation for refractory heart failure. On multivariate Cox regression analysis, high BNP concentration was an independent predictor of death or transplantation (HR 3.05, CI: 1.06–8.83, p=0.04). ConclusionsHigh BNP concentration at the first palliative stage towards Fontan circulation reflects high wall stress due to high volume load and insufficient ventricular hypertrophy. Moreover, high BNP levels at this stage were independently related to long-term outcome. BNP may be used as a guide to identify patients with high workload due to inadequate adaptation to hemodynamic load, who are at high risk.