Increased Brain Natriuretic Peptide Levels Research Articles

Association of Cardiac MRI-derived Aortic Stiffness with Early Stages and Progression of Heart Failure with Preserved Ejection Fraction.

Purpose To investigate if aortic stiffening as detected with cardiac MRI is an early phenomenon in the development and progression of heart failure with preserved ejection fraction (HFpEF). Materials and Methods Both clinical and preclinical studies were performed. The clinical study was a secondary analysis of the prospective HFpEF stress trial (August 2017 through September 2019) and included 48 participants (median age, 69 years [range, 65-73 years]; 33 female, 15 male) with noncardiac dyspnea (NCD, n = 21), overt HFpEF at rest (pulmonary capillary wedge pressure [PCWP] ≥ 15 mm Hg, n = 14), and masked HFpEF at rest diagnosed during exercise stress (PCWP ≥ 25 mm Hg, n = 13) according to right heart catheterization. Additionally, all participants underwent echocardiography and cardiac MRI at rest and during exercise stress. Aortic pulse wave velocity (PWV) was calculated. The mechanistic preclinical study characterized cardiac function and structure in transgenic mice with induced arterial stiffness (Runx2-smTg mice). Statistical analyses comprised nonparametric and parametric comparisons, Spearman correlations, and logistic regression models. Results Participants with HFpEF showed increased PWV (NCD vs masked HFpEF: 7.0 m/sec [IQR: 5.0-9.5 m/sec] vs 10.0 m/sec [IQR: 8.0-13.4 m/sec], P = .005; NCD vs overt HFpEF: 7.0 m/sec [IQR: 5.0-9.5 m/sec] vs 11.0 m/sec [IQR: 7.5-12.0 m/sec], P = .01). Increased PWV correlated with higher PCWP (P = .006), left atrial and left ventricular long-axis strain (all P < .02), and N-terminal pro-brain natriuretic peptide levels (P < .001). Participants with overt HFpEF had higher levels of myocardial fibrosis, as demonstrated by increased native T1 times (1199 msec [IQR: 1169-1228 msec] vs 1234 msec [IQR: 1208-1255 msec], P = .009). Aortic stiffness was independently associated with HFpEF on multivariable analyses (odds ratio, 1.31; P = .049). Runx2-smTG mice exhibited an "HFpEF" phenotype compared with wild-type controls, with preserved left ventricular fractional shortening but an early and late diastolic mitral annulus velocity less than 1 (mean, 0.67 ± 0.39 [standard error of the mean] vs 1.45 ± 0.47; P = .004), increased myocardial collagen deposition (mean, 11% ± 1 vs 2% ± 1; P < .001), and increased brain natriuretic peptide levels (mean, 171 pg/mL ± 23 vs 101 pg/mL ± 10; P < .001). Conclusion This study provides translational evidence that increased arterial stiffness might be associated with development and progression of HFpEF and may facilitate its early detection. Keywords: MR Functional Imaging, MR Imaging, Animal Studies, Cardiac, Aorta, Heart ClinicalTrials.gov identifier NCT03260621 Supplemental material is available for this article. © RSNA, 2024.

BNP protects against diabetic cardiomyopathy by promoting Opa1-mediated mitochondrial fusion via activating the PKG-STAT3 pathway

Brain natriuretic peptide (BNP) belongs to the family of natriuretic peptides, which are responsible for a wide range of actions. Diabetic cardiomyopathy (DCM) is often associated with increased BNP levels. This present research intends to explore the role of BNP in the development of DCM and the underlying mechanisms. Diabetes was induced in mice using streptozotocin (STZ). Primary neonatal cardiomyocytes were treated with high glucose. It was found that the levels of plasma BNP started to increase at 8 weeks after diabetes, which preceded the development of DCM. Addition of exogenous BNP promoted Opa1-mediated mitochondrial fusion, inhibited mitochondrial oxidative stress, preserved mitochondrial respiratory capacity and prevented the development of DCM, while knockdown of endogenous BNP exacerbated mitochondrial dysfunction and accelerated DCM. Opa1 knockdown attenuated the aforementioned protective action of BNP both in vivo and in vitro. BNP-induced mitochondrial fusion requires the activation of STAT3, which facilitated Opa1 transcription by binding to its promoter regions. PKG, a crucial signaling biomolecule in the BNP signaling pathway, interacted with STAT3 and induced its activation. Knockdown of NPRA (the receptor of BNP) or PKG blunted the promoting effect of BNP on STAT3 phosphorylation and Opa1-mediated mitochondrial fusion. The results of this study demonstrate for the first time that there is a rise in BNP during the early stages of DCM as a compensatory protection mechanism. BNP is a novel mitochondrial fusion activator in protecting against hyperglycemia-induced mitochondrial oxidative injury and DCM through the activation of NPRA-PKG-STAT3-Opa1 signaling pathway.

The influence of atrial fibrillation on the prognostic value of brain natriuretic peptide (BNP) in risk assesment of paroxysmal ventricular tachycardia

Introduction. Brain natriuretic peptide (BNP) as marker of higher left ventricular myocardial mechanical stress has a strong prognostic value in patients with heart failure (HF). Elevated BNP levels are associated with the of malignant ventricular arrhythmias. Atrial fibrillation (AF) is known to futher elevate BNP levels and this can influence on BNP prognostic value. The aim of the study was to assess the predictive value of BNP in risk assessment of paroxysmal ventricular tachycardia (PVT) in patients with HF and AF. Materials and methods. Totally, 92 patients with sustained or persistent AF, HF with left ventricular ejection fraction &lt; 50 %. All patients underwent transthoratic echocardiography; 24-hour ECG monitoring to assess the ventricular arrhythmia burden. BNP determination by enzyme immunoassay in venous blood serum. Results. Patients with HF, AF and PVTcompared with patients with HF and AF without PVT have higher levels of BNP (298,8 [149; 500,6] pg/ml versus 152 [145,7; 335,4] pg/ml, р = 0,02). There is a significant positive correlation between the level of BNP and the amount of PVT per 24 hours (r = 0,26; р &lt; 0,05). Increased BNP levels are associated with an increased risk of VPT, OR = 3,71 [95 % CI 1,2 to 13,1]. Discussion. BNP is a novel biomarker to improve risk stratification of sudden cardiac death not only for patients in sinus rhythm but for patients with AF. Conclusions. BNP has a predictive value in risk assessment of PVT in patients with HF and AF.

Prognostic value of brain natriuretic peptide in COVID-19 with or without acute heart failure

Abstract Background Although Brain Natriuretic Peptide (BNP) provides strong prognostic information of an unfavorable outcome in patients with acute heart failure (AHF), there is little information of its relevance as a biomarker for outcomes in COVID-19 and its complications Purpose To evaluate the association of increased BNP levels with complications and in-hospital mortality in a cohort of hospitalized COVID-19 patients. Methods The study included COVID-19 patients with data on BNP levels included in the ISACS COVID-19 registry. The population was categorized according to the presence of peak BNP levels ≥100 pg/mL during hospitalization. Primary outcomes included in-hospital mortality, AHF or acute respiratory failure (ARF, defined as PiO2/FiO2&amp;lt;300 mmHg or need for mechanical ventilation). Calculations were conducted using age and sex-adjusted multivariable logistic regression analyses. Results were also stratified according to presence or absence of cardiovascular disease (CVD) history. Differences between subgroups were verified for statistical significance using test for interaction. Results Of the 1152 patients included in the study, 615 (53.4%) had elevated BNP levels. These subjects were older (69.9±13.8 vs 59.1±16.8, p-value&amp;lt;0.001), had higher rates of cardiovascular risk factors (82.9% vs 57.7%, p-value&amp;lt;0.001) and presented more frequently with a prior history of CVD (either ischemic heart disease, cerebrovascular disease, venous thromboembolism, atrial fibrillation or a history of revascularization) (50.1% vs 27.5%, p-value&amp;lt;0.001). No sex differences were observed. When considering outcomes, BNP levels ≥100 pg/mL were associated with increased rates of in-hospital mortality (32.9% vs 4.9%, p-value&amp;lt;0.001), even after adjustment for demographic characteristics (OR: 7.35; 95% CI: 4.75–11.40; p-value&amp;lt;0.001). High BNP levels were also strongly associated with an increased risk of AHF (OR 19.9; 95% CI 8.6–45.9; p-value&amp;lt;0.001), a correlation that persisted both in patients with and without a prior CVD history (p for interaction=0.29). Of note, patients with elevated BNP also had a higher likelihood of developing ARF (OR 2.7; 95% CI 2.1–3.6; p-value&amp;lt;0.001), even in absence of AHF (OR 3.00; 95% CI 2.20–4.1; p-value&amp;lt;0.001). Conclusions In COVID-19, blood BNP level not only appears to be predictor of in-hospital mortality and AHF but was also independently associated with an increased risk of ARF. This finding supports the routine use of BNP in all patients admitted to hospital for COVID-19, regardless of a prior history of CVD. Funding Acknowledgement Type of funding sources: None.

Pooled Analysis of Central Venous Pressure and Brain Natriuretic Peptide Levels in Patients With Extubation Failure

Purpose: Cardiac insufficiency has been considered to be a common cause of extubation failure. Some studies have shown that central venous pressure (CVP) and brain natriuretic peptide (BNP) are able to predict extubation outcomes. Therefore, we conducted a pooled analysis to evaluate the potential of CVP and BNP levels as predictors of extubation outcomes, using a cohort of critically ill patients who were on mechanical ventilation (MV). Methods: We searched three online electronic databases up to October 2021. All data were analyzed using Review Manager 5.4. For each study, the analysis was performed using standardized mean differences (SMD) with 95% confidence intervals (CI). Results: The pooled analysis of seven studies on CVP levels and extubation outcomes showed that elevated CVP levels were significantly associated with extubation failure (SMD:0.47, 95% CI: 0. 43–0.51, p < 0.00001). This association also appeared before extubation (SMD:0.47, 95% CI: 0. 43–0.51, p < 0.00001), but it did not appear after extubation (SMD: 0.63, 95% CI: −0.05–1.31, p=0.07). Similarly, pooled analysis of eight studies on BNP levels and extubation outcomes showed that increased BNP levels are closely related to extubation failure (SMD:0.68, 95% CI: 0.49–0.86, p < 0.00001). This relationship also occurs before (SMD: 0.57, 95% CI: 0.35–0.79, p < 0.00001) and after (SMD: 0.91, 95% CI: 0.59–1.23, p < 0.00001) extubation. Conclusions: This study showed that elevated CVP and BNP levels are associated with extubation failure in critically ill patients. However, BNP levels are more valuable than CVP levels in predicting extubation outcomes.

Pooled analysis of central venous pressure and brain natriuretic peptide levels in patients with extubation failure

Background: extubation failure is related to prolonged hospital stay, high mortality and care cost. In recent years, cardiovascular insufficiency has been considered as a common cause of failed extubation, and some studies have shown that central venous pressure (CVP) and brain natriuretic peptide (BNP) can predict the extubation outcome. Therefore, we conducted a pooled analysis to evaluate that the CVP and BNP levels in critically ill patients subjected to mechanical ventilation are predictors of extubation failure.&#x0D; Methods: Three online electronic databases such as web of science, EMBASE, and Cochrane Library are systematically searched up to October 2021. All data are analyzed using Review Manager 5.4. The pooled analysis results were performed depending on standardized mean differences (SMD) with 95 % confidence intervals (CI) of the CVP and BNP levels for each study.&#x0D; Results: A total of 13 studies with 47 561 participants were included in our study. Our results showed that elevated CVP levels were significantly associated with the risk of failed extubation (SMD: 0.54, 95 % CI: 0.07 to 1.02, P = 0.03). This association also appeared after extubation (SMD: 1.39, 95 % CI: 0.37 to 2.40, P = 0.008), but it did not appear before extubation (SMD: 0.04, 95 % CI: -0.50 to 0.59, P = 0.88). Similarly, Our results also showed that increased BNP levels is closely related to extubation failure (SMD: 0.72, 95 % CI: 0.48 to 0.96, P &lt; 0.00001). This relationship also occurs before (SMD: 0.60, 95 % CI: 0.29 to 0.90, P = 0.0001) and after (SMD: 0.92, 95 % CI: 0.54 to 1.30, P &lt; 0.00001) extubation.&#x0D; Conclusions: This study showed that elevated CVP and BNP levels are associated with risk of extubation failure in critically ill patients. Compared with CVP level, BNP level is a more sensitive and accurate predictor of extubation failure.

A randomized controlled trial of renin-angiotensin-aldosterone system inhibitor management in patients admitted in hospital with COVID-19

BackgroundRenin-angiotensin aldosterone system inhibitors (RAASi) are commonly used among patients hospitalized with a severe acute respiratory syndrome coronavirus 2 infection coronavirus disease 2019 (COVID-19). We evaluated whether continuation versus discontinuation of RAASi were associated with short term clinical or biochemical outcomes.MethodsThe RAAS-COVID-19 trial was a randomized, open label study in adult patients previously treated with RAASi who are hospitalized with COVID-19 (NCT04508985). Participants were randomized 1:1 to discontinue or continue RAASi. The primary outcome was a global rank score calculated from baseline to day 7 (or discharge) incorporating clinical events and biomarker changes. Global rank scores were compared between groups using the Wilcoxon test statistic and the negative binomial test (using incident rate ratio [IRR]) and the intention-to-treat principle.ResultsOverall, 46 participants were enrolled; 21 participants were randomized to discontinue RAASi and 25 to continue. Patients’ mean age was 71.5 years and 43.5% were female. Discontinuation of RAASi, versus continuation, resulted in a non-statistically different mean global rank score (discontinuation 6 [standard deviation [SD] 6.3] vs continuation 3.8 (SD 2.5); P = .60). The negative binomial analysis identified that discontinuation increased the risk of adverse outcomes (IRR 1.67 [95% CI 1.06-2.62]; P = .027); RAASi discontinuation increased brain natriuretic peptide levels (% change from baseline: +16.7% vs -27.5%; P = .024) and the incidence of acute heart failure (33% vs 4.2%, P = .016).ConclusionRAASi continuation in participants hospitalized with COVID-19 appears safe; discontinuation increased brain natriuretic peptide levels and may increase risk of acute heart failure; where possible, RAASi should be continued.

Abstract 9009: Management of Renin-Angiotensin-Aldosterone System Blockade in Patients Admitted in Hospital With Confirmed Coronavirus Disease (COVID-19) Infection: The McGill RAAS-COVID-19 Randomized Controlled Trial

Background: More data is needed on the cardiovascular impact of discontinuing versus continuing renin-angiotensin aldosterone system inhibitors (RAASi) among patients hospitalized with a severe acute respiratory syndrome coronavirus 2 infection (COVID-19). Methods: The McGill RAAS-COVID-19 trial was a randomized, open label trial in adult patients hospitalized with COVID-19, who were previously treated with RAASi (angiotensin converting enzyme inhibitors [ACEi]/angiotensin receptor blocker [ARB]) (NCT04508985; 10/2020-03/2021). Participants were randomized 1:1 to discontinue or continue RAASi. The primary outcome was a global rank score calculated from baseline to day 7 (or discharge) incorporating clinical events and biomarker changes. Global rank scores were compared between groups using the Wilcoxon test statistic and the negative binomial test (using incident rate ratio [IRR]). All analyses were conducted using the intention-to-treat principle. Results: Overall, 21 participants were randomized to discontinue RAASi and 25 to continue. Patients’ mean age was 71.5 years and 43.5% were female. Discontinuation of RAASi, versus continuation, resulted in a similar mean global rank score (discontinuation 6 [standard deviation [SD] 6.3] vs continuation 3.8 (SD 2.5); p= 0.60), but the negative binomial analysis identified that discontinuation increased the risk of adverse outcomes (IRR 1.7 [95% CI 1.1 to 2.6]; p=0.03). Particularly, RAASi discontinuation increased brain natriuretic peptide (BNP) levels (% change from baseline: +16.7% vs. -27.5%; p= 0.02) and increased the incidence of acute heart failure (33% vs. 4.2%, p=0.03). Conclusion: Discontinuation of RAASi increased BNP levels and risk of acute heart failure in participants hospitalized with COVID-19; where possible, RAASi should be continued.

Brain Natriuretic Peptide as a Marker of Adverse Neurological Outcomes Among Survivors of Cardiac Arrest

Neurological prognosis after cardiac arrest remains ill-defined. Plasma brain natriuretic peptide (BNP) may relate to poor neurological prognosis in brain-injury patients, though it has not been well studied in survivors of cardiac arrest. We performed a retrospective review and examined the association of BNP with mortality and neurological outcomes at discharge in a cohort of cardiac arrest survivors enrolled from January 2012 to December 2016 at the Wake Forest Baptist Hospital, in North Carolina. Cerebral performance category (CPC) and modified Rankin scales were calculated from the chart based on neurological evaluation performed at the time of discharge. The cohort was subdivided into quartiles based on their BNP levels after which multivariable adjusted logistic regression models were applied to assess for an association between BNP and poor neurological outcomes as defined by a CPC of 3 to 4 and a modified Rankin scale of 4 to 5. Of the 657 patients included in the study, 254 patients survived until discharge. Among these, poor neurological status was observed in 101 (39.8%) patients that had a CPC score of 3 to 4 and 97 patients (38.2%) that had a modified Rankin scale of 4 to 5. Mean BNP levels were higher in patients with poor neurological status compared to those with good neurological status at discharge (P = .03 for CPC 3-4 and P = .02 for modified Rankin score 4-5). BNP levels however, did not vary significantly between patients that survived and those that expired (P = .22). BNP did emerge as a significant discriminator between patients with severe neurological disability at discharge when compared to those without. The area under the curve for BNP predicting a modified Rankin score of 4 to 5 was 0.800 (95% confidence interval [CI] 0.756-0.844, P < .001) and for predicting CPC 3 to 4 was 0.797 (95% CI 0.756-0.838, P < .001). BNP was able to significantly improve the net reclassification index and integrated discriminatory increment (P < .05). BNP was not associated with long-term all-cause mortality (P > .05). In survivors of either inpatient or out-of-hospital cardiac arrest, increased BNP levels measured at the time of arrest predicted severe neurological disability at discharge. We did not observe an independent association between BNP levels and long-term all-cause mortality. BNP may be a useful biomarker for predicting adverse neurological outcomes in survivors of cardiac arrest.

Clinical implications of late-onset right ventricular failure after implantation of a continuous-flow left ventricular assist device as bridge to transplantation.

The development of late-onset right ventricular failure (LoRVF) that occurs months after a continuous-flow left ventricular assist device (LVAD) is implanted is a clinical problem that warrants investigation. Our goal was to study the incidence, clinical manifestations and prognosis of LoRVF in a population of patients who received an LVAD as bridge to transplantation. Data were analysed from 97 consecutive patients who received an LVAD as bridge to transplantation and underwent a right heart catheterization at least 3 months after receiving an LVAD implantation. LoRVF was defined if both haemodynamic criteria of a central venous pressure >16 mmHg and a cardiac index <2.3 l/min/m2 were present. Clinical and echocardiographic variables, hospitalizations for heart failure and survival were compared between patients with and without LoRVF. LoRVF was diagnosed in 13% of patients after a median time of 11 months. Patients with LoRVF presented preoperative worse right ventricular (RV) dilatation and severe tricuspid regurgitation. LORVF was also associated with postoperative RV dilatation, moderate to severe tricuspid regurgitation and lower tricuspid annular plane systolic excursion. LoRVF resulted in increased brain natriuretic peptide levels and the need for diuretics, lower haemoglobin levels and a higher rate of atrial fibrillation and gastrointestinal bleeding. The rate of hospitalizations for heart failure in patients with LoRVF was 46%, and 15% required an urgent transplantation due to refractory RV failure. LoRVF decreased global survival and survival free from hospitalizations for heart failure (P < 0.0001). LoRVF after the implantation of an LVAD as bridge to transplantation is associated with higher morbidity and lower survival. The results suggest that the routine use of a right heart catheterization and transthoracic echocardiography may contribute to an early diagnosis before further severe complications due to refractory RV failure might occur. AZ-2019-521 on 10 July 2019.

Early Predictors of Heart Failure Progression in Patients After Myocardial Infarction.

Aim To identify early predictors for progression of chronic heart failure (CHF) in patients with ST-segment elevation myocardial infarction (STEMI).Material and methods The study included 113 patients with STEMI aged 52 (95 % confidence interval, 36 to 65) years. 24-h ECG monitoring was performed with assessment of ventricular late potentials, QT dispersion, heart rhythm turbulence (HRT), and heart rhythm variability (HRV); XStrain 2D echocardiograpy with determination of volumetric parameters, myocardial strain characteristics and velocities; and measurement of brain natriuretic peptide (BNP) concentrations. The endpoint was CHF progression during 48 weeks of follow-up, which was observed in 26 (23 %) patients. Based on the outcome, two groups were isolated, with CHF progression (Prg) (26(23%)) and with a relatively stable CHF postinfarction course (Stb) (87 (77 %)).Results At 12 weeks following MI, the Prg group showed increases in left ventricular (LV) end-diastolic dimension (EDD) (р&lt;0.05) and end-diastolic and end-systolic volumes (EDV, ESV), (р&lt;0.01), and EDV and ESV indexes (EDVi and ESVi, р&lt;0.01). In this group, global longitudinal strain (GLS) was decreased at 24 weeks (р&lt;0.05) and global radial strain (GRS) was decreased at 48 weeks (р=0.0003). In the Prg group, values of strain parameters (GLS, global circular strain (GCS), and GRS) were lower at all times. At 7-9 days, 24 weeks, and 48 weeks, the proportion of patients with pathological HRT was higher in the Prg group (38, 27, and 19 % for the Prg group vs 14 % (р=0.006); 3,4 % (р=0.001), and 2.3 % (р=0.002) for the Stb group, respectively). Only in the Stb group, increases in HRV were observed (SDNNi by 13 % (р=0.001), rMSSD by 24 % (р=0.0002), TotP by 49 % (р=0.00002), VLfP by 23 % (р=0.003), LfP by 22 % (р=0.008), and HfP by 77 % (р=0.002). At 7-9 days of MI, the Stb group had greater values of SDANN (р=0.013) and HfP (р=0.01). CHF progression correlated with abnormal values of turbulence onset (TO), disturbed HRT, increased BNP levels and LV ESD, and low values of GLS, GCS, and GRS. Combined assessment of HRT, LV ESD, and GLS at 7-9 days after STEMI allows identifying patients with high risk for CHF progression in the next 48 weeks.Conclusion The markers for CHF progression after STEMI include abnormal TO values, disturbed HRT, increased BNP levels and LV ESD, and low values of GLS, GCS, and GRS. The multifactor logistic regression analysis revealed early predictors of CHF in the postinfarction period, including abnormal TO, increased LV ESD, and reduced GLS.

P776 Stress ecocardiography and speckle tracking analysis in patients with heart failure and preserved ejection fraction

Abstract BACKGROUND Heart failure with preserved ejection fraction (HFpEF) is characterized by heart failure symptoms despite preserved LV systolic function together with at least one among left ventricle hypertrophy/left atrial enlargement plus diastolic dysfunction (DD) and increased brain natriuretic peptide levels. Rest echocardiography could still be normal despite patients experience HF symptoms. Speckle tracking analysis (STE) analyzes myocardial deformation and is able to identify subtle left ventricular dysfunction. PURPOSE to analyze the added value of stress echocardiography to improve diagnostic accuracy in patients with normal ejection fraction and unexplained dyspnoea by evaluating DD, lung B lines and STE. METHODS Main inclusion criteria were: suspected heart failure, EF &amp;gt; 40%, DD up to moderate at rest (E/e"&amp;lt;14), age &amp;lt; 85 and &amp;gt;18 years, satisfactory acoustic window. Exclusion criteria were: comorbidities limiting the prognosis, valvulopathy more than moderate, coronary artery disease, moderate to severe DD at rest (E/e"≥14; E/A≥2), pregnancy or lactation. Each patient underwent physical stress echo and STE by GE Vivid 7, (AFI). RESULTS After measuring diastolic function parameters variation with stress, HFpEF was diagnosed in 8 patients, who had baseline non-diagnostic echocardiogram (Table 1). In the remaining 20 patients a non-cardiac etiology of dyspnoea was diagnosed (NCD). EF did not significantly change from rest to stress either in HFpEF group (58 ± 6 vs 61 ± 8.7 p:0.62) or in DNC group (59 ± 8 vs 62.2 ± 7.4; p:0.26). GLS values tended to decrease in patients with HFpEF (-18.5 ± 2.2 at baseline vs -15.96 ± 6.67 at peak stress; p:0.33), and it was stable in DNC (-17.69 ± 1.15 at baseline vs - 18.04 ± 2.02 at peak stress; p:0.64). CONCLUSIONS Study of diastolic function during stress echocardiography is a useful diagnostic tool to reveal HFpEF in patients with dyspnea and unremarkable baseline echocardiogram. STE could offer useful adjunctive diagnostic information but further studies are needed to confirm its value. Table 1 HFpEF NCD p HFpEF NCD p GLS -18,5 ± 2,2 -17,6 ± 1,15 0,23 -15,96 ± 6,67 18,04 ± 2,02 0,26 E/A 0,8 ± 0,1 1 ± 0,7 0,55 1,67 ± 0,7 1,26 ± 0,6 0,07 E/e’ 10,1 ± 2,2 9,9 ± 3,7 0,4 16,4 ± 0,9 13,8 ± 5 0,16 PAP 25,6 ± 4,1 22,33 ± 0,55 0,57 49,8 ± 9,65 28,27 ± 4,35 0,001 LA 35,5 ± 8,5 23,44 ± 4,9 0,001 34,45 ± 4,88 27,32 ± 7,33 0,018 EF 58 ± 6 59 ± 8 0,6 61 ± 8,7 62,2 ± 7,4 0,7 Echocardiographic parameters at baseline and at peak stress in patients with HFpEF and with NCD

Reduced endothelial nitric oxide synthase activation contributes to cardiovascular injury during chronic kidney disease progression.

Major cardiovascular events are a common complication in patients with chronic kidney disease (CKD). Endothelial dysfunction can contribute to the cardiovascular injury observed in CKD. Here, we used a rat model of acute kidney injury to CKD transition to investigate heart alterations in the pathway activating endothelial nitric oxide synthase (eNOS) and its impact on the cardiac injury observed during CKD progression. Fifty male Wistar rats were subjected to sham surgery (n = 25) or bilateral renal ischemia-reperfusion (IR-CKD) for 45 min (n = 25). Rats were studied on a monthly basis up to 5 mo (n = 5). In another set of sham and IR-CKD rats, l-arginine was administered starting on the third month after renal ischemia. CKD development and cardiac alterations were monitored in all groups. CKD was characterized by a progressive increase in proteinuria and renal dysfunction that was evident after the fifth month of followup. Heart hypertrophy was observed starting on the fourth month after ischemia-reperfusion. There was a significant increase in brain natriuretic peptide levels. In the heart, IR-CKD rats had increased eNOS phosphorylation at threonine 495 and reduced eNOS-heat shock protein-90α interactions. l-Arginine administration prevented the heart alterations observed during CKD and increased eNOS coupling/dimerization and activation. In summary, CKD progression is accompanied by cardiac hypertrophy, fibrosis, oxidative stress, and increased brain natriuretic peptide levels. These alterations were associated with limited eNOS activation in the heart, which may result in reduced nitric oxide bioavailability and contribute to cardiac injury during CKD.

Comparison of Brain Natriuretic Peptide Levels to Simultaneously Obtained Right Heart Hemodynamics in Stable Outpatients with Pulmonary Arterial Hypertension.

Pulmonary arterial hypertension (PAH) is a progressive disease that requires validated biomarkers of disease severity. While PAH is defined hemodynamically by right heart catheterization (RHC), brain natriuretic peptide (BNP) is recommended by guidelines to assess disease status. Retrospectively collected data in 138 group 1 PAH patients were examined for the correlation of BNP levels to simultaneously obtained right heart catheterization (RHC). Patients were mostly Caucasian women, with functional class III symptoms, mean BNP of 406 ± 443 pg/mL, and an average right atrial pressure (RAP) of 9.9 ± 5.7 mm Hg and mean pulmonary artery pressure (mPAP) of 47.3 ± 14.7 mm Hg. Significant correlation was demonstrated between BNP and RAP (p = 0.021) and mPAP (p = 0.003). Additional correlation was seen with right heart size on echocardiography: right atrial (RAE; p = 0.04) and right ventricular enlargement (p = 0.03). An increased BNP level was an independent predictor of mortality (p < 0.0001), along with RAP (p = 0.039) and RAE (p = 0.018). Simultaneous collection of BNP at the time of RHC confirmed the correlation of BNP with right heart hemodynamics. The current results reinforce the use of BNP level as a continuous variable to assess disease severity in group 1 PAH.

Pregnancy and delivery outcomes from patients with repaired anomalous origin of the left coronary artery from the pulmonary artery.

We investigated the clinical courses before and during pregnancy and after delivery in patients with repaired anomalous origin of the left coronary artery from the pulmonary artery to determine the impact of the hemodynamic changes and cardiac function on the selection of the appropriate mode of delivery. Six patients who underwent coronary artery reimplantation delivered 10 infants. We scrutinized the patients' hemodynamic changes on echocardiographs and the plasma brain natriuretic peptide levels before and during pregnancy and after delivery, the perinatal outcomes and maternal and fetal events. All patients were asymptomatic and categorized as having New York Heart Association functional class I before pregnancy. In 8 of 10 pregnancies, vaginal deliveries were performed; two elective cesarean sections were performed because of symptomatic heart failure. The hemodynamic parameters were stable throughout pregnancy and postdelivery, and no maternal or fetal events occurred in the patients who underwent vaginal deliveries. One cesarean section patient developed significant heart failure during the late second and third trimesters, which was accompanied by hemodynamic changes, including increased brain natriuretic peptide levels, left ventricular diastolic dysfunction and worsening arrhythmias, and thrombosis and post-partum hemorrhage occurred postdelivery. The baby had intrauterine growth retardation and small for gestational age. None of the babies had congenital anomalies. Pregnancy was safe in most of the asymptomatic patients long after anomalous origin of the left coronary artery from the pulmonary artery was repaired. Symptomatic heart failure might occur during pregnancy in patients with persisting myocardial damage. Pregnancy and delivery should be carefully managed.

Brain Natriuretic Peptide Levels in Acute Inferior Myocardial Infarction.

BackgroundOur objective was to evaluate the relationship between initial serum brain natriuretic peptide (BNP) levels and right ventricular functions in inferior myocardial infarction (MI) with and without right ventricular involvement.MethodsThe study included 61 patients, who presented with acute inferior MI. Twenty-seven patients had right ventricular involvement. Blood samples for BNP were obtained from each patient on admission. Echocardiographic assessments were performed and recorded during the first 12 h. Right ventricular involvement was determined by electrocardiography, conventional and tissue Doppler echocardiography (TDI).ResultsIn inferior MI with right ventricular involvement, tricuspid annulus planimetric systolic excursion (TAPSE) and right ventricular fractional area change were lower, and left ventricular E/E’ ratio was higher. In the group with BNP levels above 400 pg/mL, left ventricular end-diastolic diameter and left ventricular end-systolic diameter were higher, and left ventricular ejection fraction and TAPSE, indicator of right ventricular systolic function, were lower. The elevated BNP levels were negatively correlated with RSm and TAPSE, while they were positively correlated with the E/E’ ratio. The systolic blood pressure and left ventricular end-diastolic diameter during admission were independent predictors of BNP levels.ConclusionsIn acute inferior MI, initially increased BNP levels may be valuable in predicting the right ventricle involvement. Higher rates of hypotension, right ventricular dysfunction and increased left ventricle diameters are observed in patients with BNP levels ≥ 400 pg/mL.

Correlations of plasma levels of brain natriuretic peptide and Meprin-α with the severity of coronary-artery stenosis

Objective To explore the relationship of the severity of coronary-artery stenosis with plasma levels of brain natriuretic peptide (BNP) and Meprin-α. Methods Totally 237 patients in our hospital were divided into control group (CON group), stable angina group (SA group) and acute coronary syndrome group (ACS group), according to coronary artery angiography. Patients with acute coronary syndrome were divided into 3 subgroups: unstable angina (UA) group, non-ST segment elevation myocardial infarction (NSTEMI) group and ST segment elevation myocardial infarction (STEMI) group. Patients with coronary artery disease (CAD) were divided into 3 subgroups: low-score, medium-score and high-score groups, according to coronary angiography and Syntax score. BNP and Meprin-α levels were determined in patients with coronary artery disease, and the degree of coronary artery stenosis was evaluated. The differences in above indexes were analyzed and compared among the three groups. Results Plasma levels of BNP and Meprin-α were higher in ACS group than in CON group 〔(233.16±78.22)ng/L vs. (33.48±13.71)ng/L, (26.89±6.45)nmol/L vs. (12.83±0.66)nmol/L, both P<0.05〕. Compared with UA group, plasma levels of BNP and Meprin-α were increased in NSTEMI and STEMI groups (all P<0.05). Compared with the control group, plasma levels of BNP and Meprin-α in the Syntax scores-divided subgroups were increased (all P< 0.05). The plasma levels of BNP and Meprin-α in CAD patients were significantly increased along with the increase of Syntax Score. Spearman correlation analysis showed that low density lipoprotein cholesterol, glucose, BNP and Meprin-α levels had positive correlations with the occurrence of coronary heart disease, while high density lipoprotein level was negatively correlated with the occurrence of coronary heart disease (all P<0.05). Conclusions BNP and Meprin-α levels in peripheral blood are significantly elevated in patients with coronary heart disease, and they are correlated with Syntax score. The risk of ACS is increased along with the increased BNP and Meprin-α levels. Key words: Coronary Stenosis; Natriuetic peptid, brain; Peptide hydrolases

Prevalence and Clinical Determinants of Left Atrial Appendage Thrombus in Patients With Atrial Fibrillation Before Pulmonary Vein Isolation

The CHADS2 score is considered a reliable predictor of stroke/thromboembolism risk in patients with atrial fibrillation (AF). However, thromboembolism can occasionally occur even in patients with AF with low CHADS2 score (CHADS2 score= 0 or 1). To investigate the incidence and predictors of left atrial appendage (LAA) thrombus (LAAT) formation in patients with AF, we studied consecutive 543 Japanese patients with AF who underwent transesophageal echocardiography before pulmonary vein isolation from 2008 to 2012. All patients were treated with anticoagulation therapy with warfarin, and their clinical and echocardiographic characteristics were evaluated. LAATs were observed in 35 (6.4%) of 543 patients, and the prevalence was clearly correlated with the patient's CHADS2 scores. Of 338 patients with low CHADS2 score, LAATs were observed in 7 patients (2.1%). By multivariate analysis, increased left atrial volume (≥50ml), decreased ejection fraction (<56%), and increased brain natriuretic peptide level (>75 pg/ml) were significantly associated with increased prevalence of LAATs, even in patients with low CHADS2 score. Accordingly, we proposed a new scoring system to predict LAAT (left atrial volume ≥50ml: score 2; ejection fraction <56%: score 1; brain natriuretic peptide >75 pg/ml: score 1). Patients with a score ≥2 have a greater risk of LAAT, whereas all patients with score ≤1 have no LAATs. Our scoring system is useful for evaluation of the risk of LAAT in patients with AF even with low CHADS2 score.

The Impact of Obstructive Sleep Apnea Syndrome on Nocturnal Urine Production in Older Men With Nocturia

To investigate the impact of obstructive sleep apnea syndrome (OSAS) on night-time secretion of brain natriuretic peptide (BNP) and antidiuretic hormone (ADH) in older men with nocturia accompanied by nocturnal polyuria. One hundred six men with nocturia aged ≥ 60 years underwent full-night polysomnography to determine whether they had OSAS. Blood count, standard chemistry panel, BNP, urinary ADH, urinary creatinine (u-Cre), and urinary osmolarity were measured at 6:00 AM, and a frequency volume chart was recorded on the same day that polysomnography was performed. We evaluated 83 patients after excluding 18 with mild OSAS and 5 with nocturnal polyuria index <0.35. Participants with OSAS had higher apnea-hypopnea index (P < .0001) than those without OSAS. Body mass index and systolic blood pressure were higher in OSAS patients than those in the control group. BNP was higher in the OSAS patients than in the control patients (48.6 ± 41.4 vs 30.7 ± 31.5; P = .0006). On urinalysis, OSAS patients showed higher urinary sodium and u-Cre secretion than controls (24.7 ± 11.3 vs 16.2 ± 5.1; P <.0001). Urine osmolarity was also higher in OSAS patients than in the control patients (616 ± 172 vs 516 ± 174; P = .0285). There was no significant difference in urinary ADH and u-Cre (6.7 ± 10.4 vs 6.8 ± 7.8; P = .3617) between the 2 groups. Our results indicated that older men with nocturnal polyuria and OSAS did not compensate their fluid imbalance presented with decreased secretion of ADH but increased BNP level.

Gender Differences in Clinical Characteristics, Treatment and Long-Term Outcome in Patients With Stage C/D Heart Failure in Japan

The gender differences in patients with chronic heart failure (CHF) remain to be fully elucidated in the Japanese population. We examined gender differences in clinical characteristics, treatment and long-term outcome in 4,736 consecutive CHF patients in stage C/D (mean age, 69 years) out of 10,219 patients registered in the CHF Registry, named CHART-2 Study (NCT 00418041). Compared with male patients (68%, n=3,234), female patients (32%, n=1,502) were 3.8 years older and had lower prevalence of ischemic heart disease, diabetes, smoking, myocardial infarction and cancer. At baseline, women had higher prevalence of preserved left ventricular function but had higher NYHA functional class and increased brain natriuretic peptide level. In women, aspirin, β-blockers and statins were less frequently used and diuretics were more frequently used. Crude mortality rate was similar between the genders during the median 3.1-year follow-up (52.4/1,000 and 47.3/1,000 person-years for women and men, respectively, P=0.225). On multivariate Cox regression analysis, women had a reduced risk of mortality (adjusted HR, 0.791; 95% CI: 0.640-0.979, P=0.031). Substantial gender differences exist in stage C/D CHF patients in real-world practice in Japan. Although female CHF patients had better survival than male patients after adjustment for baseline differences, crude mortality rate was similar between the genders, possibly reflecting relatively severer clinical manifestations in women.