Elevated N-terminal Pro-brain Natriuretic Peptide Research Articles

Association Between Serum NT-proBNP and Gray Matter Atrophy Patterns in an Older Japanese Population: The Hisayama Study.

Several population-based studies have reported that higher serum N-terminal pro-brain natriuretic peptide (NT-proBNP) levels are associated with brain morphological changes. However, no population-based studies have examined the relationship between serum NT-proBNP and various regional brain volumes in detail. We here analyzed the brain MRI data of 1201 community-dwelling Japanese aged ≥65 years. Regional gray matter volumes (GMV) and intracranial volume (ICV) were estimated by applying voxel-based morphometry (VBM) methods. The associations of serum NT-proBNP with regional GMV/ICV were examined by analysis of covariance. The regional gray matter atrophy patterns associated with elevated serum NT-proBNP levels were investigated using VBM without a priori regions of interest. The multivariable-adjusted means of the frontal, temporal, hippocampal, parahippocampal, and entorhinal GMV/ICV decreased significantly with elevated serum NT-proBNP levels (all p for trend and q values of false discovery rate correction < .05). In VBM, elevated serum NT-proBNP levels were correlated with atrophy of the bilateral hippocampi, bilateral amygdalas, bilateral parahippocampal gyri, bilateral entorhinal areas, bilateral fusiform gyri, left middle temporal gyrus, left inferior temporal gyrus, right central operculum, right posterior orbital gyrus, bilateral middle frontal gyri, anterior cingulate gyrus and bilateral medial frontal cortices. In a sensitivity analysis excluding 254 participants with mild cognitive impairment or dementia, serum NT-proBNP levels were correlated with atrophy of the bilateral hippocampi, bilateral amygdalas, bilateral parahippocampal gyri, bilateral fusiform gyri, and left middle frontal gyrus. Our data suggest that elevated serum NT-proBNP levels are associated with gray matter atrophy in brain regions that play an important role in cognitive function.

Association of N-terminal Pro-Brain natriuretic peptide with survival among US cancer survivors.

N-terminal pro-brain natriuretic peptide (NT-proBNP) is a cardiac biomarker associated with the risk of heart failure and death in the general population but has not been explored in cancer survivors. Using a US nationally representative sample of adults ≥20 years from the National Health and Nutrition Examination Survey from 1999 to 2004, this study compared NT-proBNP levels between non-cancer adults (n = 12574) and cancer survivors (n = 787) and examined the association of NT-proBNP with all-cause and cause-specific mortality among cancer survivors. Cancer survivors had higher NT-proBNP levels than non-cancer adults (median: 125.4 [IQR, 52.4 to 286.0] vs 43.2 [IQR, 20.3-95.0]). In particular, survivors of breast, prostate, and colorectal cancers had higher NT-proBNP levels than non-cancer adults (multivariable-adjusted P<.05). 471 survivors died (cancer: 141; cardiac disease: 95) during a median follow-up of 13.4 years (9,393 person-years). Among cancer survivors, higher NT-proBNP levels were statistically associated with increased risks of all-cause (HR, 1.31 [95% CI, 1.18-1.46]) and cardiac (HR, 1.55 [95% CI, 1.21-2.00) mortality but not with death due to cancer (HR, 1.10 [95% CI, 0.92-1.32]). Higher NT-proBNP levels were associated with elevated overall mortality in survivors of prostate (HR, 1.45 [95% CI, 1.17-1.79]) and colorectal (HR, 1.78 [95% 1.12-2.85]) cancers (P-interaction = 0.169). Non-linear dose-response relationships were observed between NT-proBNP and mortality, with statistically significant relationships emerging above 125 pg/ml. Cancer survivors had higher NT-proBNP than non-cancer adults, and elevated NT-proBNP levels were associated with higher risks of all-cause and cardiac mortality in cancer survivors.

Cardiological parameters predict mortality and cardiotoxicity in oncological patients.

Oncological patients suspected at risk for cardiotoxicity are recommended to undergo intensified cardiological surveillance. We investigated the value of cardiac biomarkers and patient-related risk factors [age, cardiovascular risk factors (CVRFs), and cardiac function] for the prediction of all-cause mortality (ACM) and the development of cardiotoxicity. Between January 2016 and December 2020, patients with oncological diseases admitted to the Cardio-Oncology Unit at the Heidelberg University Hospital were included. They were evaluated by medical history, physical examination, 12-lead electrocardiogram, 2D echocardiography, and cardiac biomarkers [high-sensitivity cardiac troponin T (hs-cTnT) and N-terminal pro-brain natriuretic peptide (NT-proBNP)]. The primary endpoint was defined as ACM and the secondary endpoint was defined as cardiotoxicity, as defined by the European Society of Cardiology. Of the 1971 patients enrolled, the primary endpoint was reached by 490 patients (25.7%) with a median of 363.5 [interquartile range (IQR) 121.8, 522.5] days after presentation. Hs-cTnT of ≥ 7ng/L [odds ratio (OR) 1.82, P<0.001] and NT-proBNP (OR 1.98, P<0.001) were independent predictors of ACM, while reduced left ventricular ejection fraction was not associated with increased ACM (P=0.85). The secondary endpoint was reached by 182 patients (9.2%) with a median of 793.5 [IQR 411.2, 1165.0] days. Patients with multiple CVRFs (defined as high risk, n=886) had an increased risk of cardiotoxicity (n=100/886, 11.3%; hazard ratio 1.57, P=0.004). They showed elevated baseline values of hs-cTnT (OR 1.60, P=0.006) and NT-proBNP (OR 4.00, P<0.001) and had an increased risk of ACM (OR 1.43, P=0.031). In cancer patients, CVRF accumulation predicts cardiotoxicity whereas elevated hs-cTnT or NT-proBNP levels are associated with ACM. Accordingly, less intensive surveillance protocols may be warranted in patients with low cardiac biomarker levels and absence of CVRFs.

Abstract 17187: The Relationship Between N-Terminal Pro-Brain Natriuretic Peptide Levels and Poor Outcomes in Covid-19 Patients

Introduction: N-terminal pro-brain natriuretic peptide (NT-proBNP) is a biomarker reflecting increased cardiac stress. It is a key variable in assessing patients with various pathologies. However, assessment of NT-proBNP as a variable in the prognostication of poor outcomes in COVID-19 patients is lacking. In addition, COVID-19 has brought its own variables and sequelae along with overlapping pathologies in a variety of systems. Hypothesis: With the systemic impact that COVID-19 can have, NT-proBNP represents a variable that will aid in identifying patients at higher risk of poor outcomes. We aim to assess the utility of NT-proBNP to help predict the incidence of major adverse cardiovascular events (MACE) and mortality in patients hospitalized with COVID-19. Methods: Using a multi-center observational database, we analyzed 1,692 hospitalized COVID-19 PCR-positive patients at Methodist Health System from March to July 2020. We examined NT-proBNP levels, in-hospital death or hospice referral rates, and incidence of MACE in the cohort. MACE was defined as congestive heart failure (CHF) exacerbation, pericardial effusion, cardiac tamponade, myocarditis, pericarditis, myocardial infarction (MI), stroke, pulmonary embolism/deep vein thrombosis, or shock. The incidence of mortality and MACE were compared between patients with and without elevated NT-proBNP levels. Elevated NT-proBNP levels were those &gt;900 pg/mL. A chi-square ( X 2 ) and odds ratio (OR) test were used to analyze observed variables. Results: Of the 1,692 hospitalized patients, 576 patients (34.0%) arrived with elevated NT-proBNP levels. Patients with elevated NT-proBNP had a higher incidence of mortality (OR=3.2559, 95% CI=2.522-5.203, p&lt;0.0001) and MACE (OR=6.564, 95% CI=5.255-8.199, p&lt;0.0001) compared to patients with NT-proBNP levels &lt;900 pg/mL. Additionally, the elevated NT-proBNP patients had a higher incidence of CHF exacerbation, MI, and shock compared to patients with NT-proBNP levels &lt;900 pg/mL. Conclusions: NT-proBNP levels can be a vital tool in recognizing COVID-19 patients who are at higher risk of poor outcomes. The use of NT-proBNP can further aid in prognostication in patients presenting to the hospital with COVID-19.

Changes of myocardial dysfunction and injury biomarkers over chemotherapy for multiple myeloma: difficulties in laboratory data interpretation

Aim. To study the changes of the levels of cardiac biomarkers (N-terminal pro-brain natriuretic peptide (NT-proBNP) and high-sensitivity troponin I (hsTnI)) in patients with newly diagnosed multiple myeloma (MM) during programmatic treatment with bortezomib (VCd regimen).Material and methods. This prospective pilot study included patients with a newly diagnosed MM (n=30), who were scheduled for a cycle of chemotherapy including a proteasome inhibitor (bortezomib). All patients underwent standard laboratory (complete blood count, biochemical tests, serum protein electrophoresis), electrocardiography, echocardiography, as well as the level of specific laboratory markers of myocardial dysfunction (NT-proBNP) and injury (hsTnI) was determined immediately before treatment, after 3 and 6 cycles of chemotherapy.Results. The mean age was 63,8±10 years with a slight predominance of men (56,7%, n=17). The patients initially had an increased level of NT-proBNP (316 [75,9; 602,6] pg/mL) with its decrease to 144,0 [102,3; 294,0] pg/ml after 3 cycles and to 109,2 [59,9; 344,5] pg/ml after 6 cycles of chemotherapy. At the MM onset, the mean hsTnI values were 0,06 [0,03; 0,49] ng/mL, whereas after 3 and 6 chemotherapy cycles it accounted for 0,02 [0,01-0,68] and 0,65 [0,02; 1,51] ng/ml, respectively, with the normal range of less than 0,1 ng/ml. Despite this, no statistical significance has been obtained. There were no clinical and/or laboratory signs of heart failure, ischemia, or other non-cardiac causes of elevated NT-proBNP levels in this cohort. Multivariate regression analysis revealed the following significant factors influencing the initial hsTnI level: paraprotein, hemoglobin and erythrocyte sedimentation rate (ESR). The resulting regression model was characterized by a strong correlation (r=0,702, p&lt;0,001).Conclusion. MM and its pathogenetic features such as paraproteinemia may be challenging for NT-proBNP and hsTnI levels assessment in group of interest before treatment. An unreliable assessment of these markers before chemotherapy may lead to incorrect baseline cardiovascular risk stratification and make it difficult for a cardiologist/cardio-oncologist to choose proper management strategy.

Variations in NT-proBNP Levels in Pregnant Patients with and without SARS-CoV-2 Infection: Consequences for the Newborns.

NT-proBNP (N-terminal pro-brain natriuretic peptide) has a high negative predictive value for ruling out heart failure, a disorder linked with volume overload of the ventricles, and is used for diagnosis, prognosis, and risk stratification. Pregnancy causes in healthy women changes in physical and hemodynamic parameters and appears to be a risk factor for severe COVID-19 illness. The purpose of this study is to highlight the significance of monitoring NT-proBNP levels during pregnancy, particularly in patients who were infected with COVID-19 during pregnancy or were infected with the virus while giving birth. The findings of this comparative research indicate the importance of NT-proBNP in terms of foetal prognosis and birthweight. We collected blood samples to measure NT-proBNP concentrations from a cohort of 186 pregnant patients divided into two groups based on the presence of SARS-CoV-2 viral infection. Elevated NT-proBNP had an unfavourable implication on the newborn birth weight and Apgar score and expressed its influence on lower values. We consider that NT-proBNP testing in pregnant patients, especially those with COVID-19 infection, can be relevant and be used as a predictive marker to be taken into consideration when it comes to management, outcome, and treatment regarding pregnant patients and their newborns.

Clinical Implication of N-Terminal Pro-Brain Natriuretic Peptide Burden in Heart Failure With Reduced Ejection Fraction: From the GUIDE-IT

AimsThe aim of the study was to explore the prognostic implication of N-terminal pro-brain natriuretic peptide (NT-proBNP) burden on heart failure with reduced ejection fraction (HFrEF). MethodsWe performed a post-hoc analysis of the GUIDing Evidence Based Therapy Using Biomarker Intensified Treatment in Heart Failure (GUIDE-IT) trial. NT-proBNP burden was defined as the proportion of days with elevated NT-proBNP (≥1800 pg/ml) to the whole observation time. Cox proportional hazards regression model was used to evaluate the association with NT-proBNP burden and prognosis. ResultsA total of 815 patients with HFrEF were analyzed in our study. Patients were categorized into 4 groups according to the degree of NT-proBNP burden. In the multivariate cox analysis, NT-proBNP burden was significantly associated with all-cause mortality, cardiovascular (CV) mortality and HF hospitalization. Compared to patients without NT-proBNP burden, the risk for composite outcome increased by 210% (HR 3.10, 95% CI 1.72-5.58, p<0.001) in NT-proBNP burden 1 (mild) group, 432% (HR 5.32, 95% CI 2.93-9.67, p<0.001) in NT-proBNP burden 2 (moderate) group and over 12 times (HR 13.15, 95% CI 7.42-23.33, p<0.001) in NT-proBNP burden 3 (severe) group. Sensitivity analyses stratified by age and renal function yielded similar results. ConclusionsHigher NT-proBNP burden was associated with significant increase in risks of all-cause mortality, CV mortality, HF hospitalization and composite outcome. The results suggested that NT-proBNP burden could be an important predictor of the prognosis of patients with HFrEF.

Relationship of atrial fibrillation and N terminal pro brain natriuretic peptide in heart failure patients.

N terminal pro brain natriuretic peptide (NT-proBNP) plays an important role in the diagnosis and prognosis of heart failure (HF). The plasma level of NT-proBNP in atrial fibrillation (AF) patients was higher than of sinus rhythm patients. In HF, NT-proBNP levels are affected by the concomitant presence of AF, making it difficult to distinguish between HF and AF in patients with elevated NT-proBNP. Several other diseases, such as renal failure and pulmonary embolism, are known to further increase NT-proBNP levels in patients with concomitant HF. Therefore, NT-proBNP is a sensitive but non-specific marker for the detection of HF. AF is very important in this regard because among patients with HF regardless of ejection fraction, symptoms such as shortness of breath and atrial enlargement develop and can mimic HF. In the present study, we investigated whether the prognostic value of natriuretic peptides in HF holds true for patients with concomitant AF.

Causes of hypercapnic respiratory failure: a population-based case-control study

ObjectiveThere are no population-based data on the relative importance of specific causes of hypercapnic respiratory failure (HRF). We sought to quantify the associations between hospitalisation with HRF and potential antecedent causes including chronic obstructive pulmonary disease (COPD), obstructive sleep apnea, and congestive cardiac failure. We used data on the prevalence of these conditions to estimate the population attributable fraction for each cause.MethodsA case–control study was conducted among residents aged ≥ 40 years from the Liverpool local government area in Sydney, Australia. Cases were identified from hospital records based on PaCO2 > 45 mmHg. Controls were randomly selected from the study population using a cluster sampling design. We collected self-reported data on medication use and performed spirometry, limited-channel sleep studies, venous sampling for N-terminal pro-brain natriuretic peptide (NT-proBNP) levels, and sniff nasal inspiratory pressure (SNIP) measurements. Logistic regression analyses were performed using directed acyclic graphs to identify covariates.ResultsWe recruited 42 cases and 105 controls. HRF was strongly associated with post-bronchodilator airflow obstruction, elevated NT-proBNP levels, reduced SNIP measurements and self-reported opioid medication use. There were no differences in the apnoea-hypopnea index or oxygen desaturation index between groups. COPD had the highest population attributable fraction (42%, 95% confidence interval 18% to 59%).ConclusionsCOPD, congestive cardiac failure, and self-reported use of opioid medications, but not obstructive sleep apnea, are important causes of HRF among adults over 40 years old. No single cause accounts for the majority of cases based on the population attributable fraction.

BASELINE CARDIAC BIOMARKER ANALYSIS FROM THE BASEL POSTPARTUM HYPERTENSION REGISTRY

Objective: Postpartum hypertension (PPHT) is defined by elevated blood pressure measurements after birth of more than 140 mmHg systolic and more than 90 mmHg diastolic, that persist or develop directly after pregnancy and is associated with adverse cardiovascular and renal outcome. Aim of the current analysis was the evaluation of different prognostic cardiac and stress related biomarkers like cardiac troponin T (cTnT), N-terminal pro-Brain Natriuretic Peptide (NT-proBNP) and growth differentiation factor 15 (GDF-15) in the setting of PPHT. Design and method: Enrollment for the prospective observational Basel Postpartum Hypertension Registry began in June 2020 at the University Hospital Basel. Women with preexisting hypertension, hypertensive disorders of pregnancy (HDP), and de novo postpartum hypertension were enrolled and followed up in structured management program. Clinical history and lab values were collected out of the electronic health records. Additional blood samples were stored for further evaluation. The present analysis contains biomarker analysis of a subset of 58 out of 288 patients using blood samples taken within one week of giving birth. Serum samples were analyzed for detectable levels of cTnT, NT-proBNP and GDF-15 at the department for Laboratory Medicine at University Hospital Basel using electrochemiluminescence immunoassay Elecsys on the Cobas e 801 platform (Roche Diagnostics, Rotkreuz, Switzerland). Results: Mean age of the patients from whom we measured biomarkers at baseline was 34±4.7. Mean troponin was 8.5 ng/l ±2.2 with normal cuttoffs for this age group being 14ng/l and sex specific cutoffs at 9ng/l. NT-proBNP was 229.86ng/l ±80.4, with 125ng/l being the normal cut off in an acute disease setting. Mean GDF-15 was 1895.8ng/l ±323.5 with correlating normal values in healthy populations in the same age range being 564 ± 223 ng/l. Conclusions: This first biomarker analysis shows a trend of elevated NT-proBNP and GDF-15 which are associated with cardiovascular disease or stress. Cardiac troponin T was not elevated in most of the patients, but in a subset of 13 patients. Further analysis and long term outcome correlations remains to be established and may be part of the follow-up analyses of the Basel PPHT cohort.

Elevated NT-proBNP predicts unfavorable outcomes in patients with acute ischemic stroke after thrombolytic therapy

ObjectiveFew studies correlated n-terminal pro-brain natriuretic peptide (NT-proBNP) with early neurological deterioration (END) and prognosis of acute ischaemic stroke (AIS) patients with rt-PA intravenous thrombolysis. Therefore this study aimed to investigate the relationship between NT-proBNP and END, and prognosis after intravenous thrombolysis in patients with AIS.MethodsA total of 325 patients with AIS were enrolled. We performed the natural logarithm transformation on the NT-proBNP [ln(NT-proBNP)]. Univariate and multivariate logistic regression analyses were performed to assess the relationship between ln(NT-proBNP) and END, and prognosis and receiver operating characteristic (ROC) curves were used to show the sensitivity and specificity of NT-proBNP.ResultsAfter thrombolysis, among 325 patients with AIS, 43 patients (13.2%) developed END. In addition, three months follow-up showed a poor prognosis in 98 cases (30.2%) and a good prognosis in 227 cases (69.8%). Multivariate logistic regression analysis showed that ln(NT-proBNP) was an independent risk factor for END (OR = 1.450,95%CI:1.072 ~ 1.963, P = 0.016) and poor prognosis at three months follow-up (OR = 1.767, 95%CI: 1.347 ~ 2.317, P < 0.001) respectively. According to ROC curve analysis, ln(NT-proBNP) (AUC 0.735, 95%CI: 0.674 ~0.796, P < 0.001) had a good predictive value for poor prognosis, with a predictive value of 5.12 and sensitivity and specificity of 79.59% and 60.35% respectively. When combined with NIHSS to predict END(AUC 0.718, 95%CI: 0.631 ~ 0.805, P < 0.001) and poor prognosis(AUC 0.780, 95%CI: 0.724 ~ 0.836, P < 0.001), the predictive value of the model is further improved.ConclusionNT-proBNP is independently associated with END and poor prognosis in patients with AIS following intravenous thrombolysis and has a particular predictive value for END and poor prognosis.

N-terminal pro-brain natriuretic peptide is a prognostic marker for response to intensive chemotherapy, early death, and overall survival in acute myeloid leukemia.

Patient-related factors are of prognostic importance in acute myeloid leukemia (AML). Likewise, cardiac disorders may limit the tolerance of intensive therapy. Little is known about the prognostic value of N-terminal pro-brain natriuretic peptide (NT-proBNP). We analyzed NT-proBNP levels at diagnosis in 312 AML patients (median age: 61 years; range 17-89 years) treated with 3 + 7-based induction-chemotherapy and consolidation with up to four cycles of intermediate or high-dose ARA-C. NT-proBNP levels were elevated in 199 patients (63.8%), normal (0-125 pg/ml) in 113 (36.2%), and highly elevated (>2000 pg/ml) in 20 patients (6.4%). Median NT-proBNP levels differed significantly among patients with complete remission (153.3pg/ml), no remission (225.9pg/ml), or early death (735.5pg/ml) (p=.002). In multivariate analysis, NT-proBNP, age, and the 2009 European LeukemiaNet (ELN-2009) classification were independent predictors of outcome after induction chemotherapy. Overall survival (OS) differed significantly between patients with normal, moderately elevated, and highly elevated NT-proBNP (p < .001). These differences were observed in all patients and in patients <60 years but not in those ≥60 years. In multivariate analysis, NT-proBNP, age, and ELN-2009 remained independent prognostic variables for OS (p < .01). Together, NT-proBNP is an independent prognostic factor indicating the risk of induction failure, early death, and reduced OS in patients with AML.

The diagnostic value of n-terminal probrain natriuretic peptides to differentiate neonatal pneumoniae and transient tachypnea of the newborn.

The primary objective of the study was to determine the diagnostic value of serum N-terminal probrain natriuretic peptide (NT-proBNP) levels to differentiate neonatal pneumonia (NP) and transient tachypnea of the newborn (TTN). The secondary objective was to investigate the prognostic role of NT-proBNP levels in neonates with severe respiratory distress (RD). A prospective, observational, single-blinded study involving 58 late preterm and term newborns who were diagnosed with TTN or NP was conducted between June 2020 and June 2021 at a level-3 neonatal intensive care unit in Kırıkkale University Faculty of Medicine. TTN and NP groups were compared for serum NT-proBNP levels measured at the 1st and 24th hours of life. Optimal cut-off NT-proBNP value was determined by Youden index to predict the diagnosis of NP. Lung ultrasound was used to support the diagnosis of TTN and NP. In addition, lung ultrasound score (LUS) was used to determine severe RD. The median of NT-proBNP level was significantly higher at the 24th hour of life in the NP group than in the TTN group, respectively 7263.5 pg/mL (1643-35,000) and 3308 pg/mL (69-19,746), p = 0.004. At a cut-off value of 5515.5 pg/mL, NT-proBNP had a sensitivity of 75% and specificity of 73.8% to predict NP [AUC= 0.749 (95% CI: 0.602-0.895; p = 0.004)]. The study population was divided into two groups as high score group (n: 23, LUS ≥ 7) and low score group (n: 35, LUS < 7) according to the LUS at the 6th hour of life. NT-proBNP values at 24th hour of life were 6320 pg/mL (69-35,000) in high score group and 3500 pg/mL (570-15,948) in low score group, p = 0.044. Duration of oxygen support (p = 0.006), noninvasive ventilation (p = 0.008) and NICU stay (p = 0.004) were higher in high-score group. NT-proBNP values at 24th hour of life can be used as a relatively early predictor in the differentiation between NP and TTN in late preterm and term neonates. In addition, elevated NT-proBNP values are related to the higher LUS which reflects the severity of RD regardless of diagnosis.

The Heavy Heart: An Unusual Cause of Ventricular Tachycardia

A 17-year-old female presented to the emergency department with a one-hour history of abdominal pain, nausea, vomiting and weakness. Physical examination on admission revealed a heart rate of 106 beats per minute, blood pressure of 136/88 mmHg and a respiratory rate of 25 breaths per minute. Her medical history was unremarkable with no prior medical comorbidities or surgical history. She denied taking any prescribed or over the counter medications. The initial ECG showed ventricular tachycardia (VT) (Figure 1), with investigations revealing a normal troponin I level of <0.03ng/ml (reference range <0.3 ng/mL), elevated N-terminal pro-brain natriuretic peptide level of 439.2 ng/L (reference range <300 ng/L) and normal serum potassium level of 4.0 mmol/L (reference range 3.5-5.3 mmol/L). Over the next hours, the patient developed shallow respirations, with rapid worsening of muscle weakness involving all four limbs. An arterial blood gas obtained on room air revealed severe acidosis (pH, 7.178) and hypoxemia (PaO2, 65.8 mmHg). A repeated blood test conducted four hours after admission noted profound hypokalemia (serum potassium, 1.9 mmol/L).

Influence of Iron Deficiency on Clinical and Haemodynamic Parameters in Pulmonary Arterial Hypertension Cohorts.

Iron deficiency (Fedef) has been shown to be common in patients with group 1 or pulmonary arterial hypertension (PAH). Several studies have shown a negative impact of Fedef on clinical and haemodynamic parameters of the disease, but data from individual studies have not been strong enough to lead to incorporation of the finding of Fedef into prognostic or therapeutic algorithms. The goal of this meta-analysis was to combine data from available studies to better define any associations between Fedef and established variables of prognostic importance in PAH. A literature search identified nine studies with extractable data relevant to the study questions. The impact of Fedef upon the following parameters was evaluated: 6-minute walk distance (6MWD), WHO-functional class, N-terminal pro-brain natriuretic peptide (NT-proBNP) levels, echocardiography, and findings from right heart catheterisation (RHC). Pooled results were reported as mean difference or risk difference with 95% confidence intervals utilising a random effects modeling approach. Fedef in the PAH population was common (47% of cases) and was associated with cardiovascular dysfunction (lower tricuspid annular plane systolic excursion [TAPSE], elevated NT-proBNP, and lower mixed venous oxygen saturation) and with reduction in functional capacity (lower 6MWD and higher functional class). This meta-analysis strengthens the relationships between Fedef and several markers of poor outcome in PAH. Fedef in patients with PAH warrants further scrutiny and merits consideration as a cause of clinical deterioration. Even though causation and longitudinal relationships between Fedef and PAH could not be identified, effect of Fedef on factors that affect disease prognosis is noteworthy and worthy of more focussed studies.

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

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

Abstract 10334: Vital Exhaustion and Cardiac Biomarkers - The Atherosclerosis Risk in Communities Study

Introduction: Vital exhaustion (VE), defined as excessive fatigue and demoralization due to chronic stress, is a risk factor for cardiovascular disease (CVD), but the mechanism is unclear. We examined the association of VE with biomarkers of cardiac injury, neurohormonal stress and inflammation in the Atherosclerosis Risk in Communities (ARIC) study. Methods: Symptoms of VE were measured at ARIC visit 2 (1990-92, n= 11,588, mean age 57) using the Maastricht Vital Exhaustion Questionnaire (MVEQ). We analyzed the association of VE with cardiac biomarkers [High-sensitivity troponin T (Hs-TnT), N-terminal pro brain natriuretic peptide (NT-proBNP), and high-sensitivity C-reactive protein (Hs-CRP)] levels in adults without known CVD. Symptoms of VE (MVEQ scores) were categorized into quartiles. Elevated biomarker levels were defined as Hs-TnT ≥ 13 ng/L, NT-proBNP ≥ 125 pg/mL, and hs-CRP ≥ 2 mg/L. Logistic regression models adjusted for demographics and comorbidities were used to test for associations. The associations of VE (MVEQ score ≥16), elevated biomarkers, or both with incident CVD events after 6-year follow up was assessed by Cox proportional hazard regression. Results: Compared with the lowest quartile of VE (MVEQ ≤ 4), the highest quartile of VE (MVEQ 16-42), in adjusted models, was associated with elevated Hs-TnT, NT-proBNP, and hs-CRP [Odds Ratio (95% confidence interval) of 1.75 (1.34-2.29, p&lt;0.01), 1.40 (1.19-1.64, p&lt;0.01), and 1.14 (1.01-1.28, p&lt;0.01), respectively]. The highest quartile of VE was associated with increased risk of CVD events. The risk was increased further in the setting of both significant VE (MVEQ ≥16) and elevated biomarkers (Table). Conclusions: Symptoms of VE are associated with elevated Hs-TnT, NT-proBNP, and Hs-CRP independent of traditional CVD risk factors. The presence of VE and elevated cardiac biomarkers is associated with high risk of incident CVD events in adults without CVD.

Inflammation and echocardiographic ventricular function in patients with a systemic right ventricle and heart failure

Abstract Background Clinical deterioration is fast once heart failure (HF) develops in patients with a systemic right ventricle (sRV) [1]. Despite its established role in HF patients with a normal heart anatomy [2,3], little is known about the contribution of inflammation in sRV-HF patients. Aims To assess inflammation and echocardiography in sRV patients with or without HF and to relate inflammation to echocardiographic ventricular function. Methods In this cross-sectional prospective study, patients with a sRV due to Senning/Mustard repair or due to congenitally corrected transposition of the great arteries (ccTGA) were consecutively enrolled at the outpatient clinic of a single, tertiary care center. Echocardiography and venipuncture were performed on the same day. C-reactive protein (CRP), red cell distribution width (RDW), neutrophil-lymphocyte ratio (NLR), myeloperoxidase (MPO), myeloperoxidase and citrullinated histone H3-DNA complexes (MPO-DNA and H3Cit-DNA) and interleukin 10 were measured. Patients were stratified based on the presence or absence of HF, with HF defined as having signs and/or symptoms of HF requiring medical therapy plus one of the following: impaired ventricular function with elevated intracardiac pressures, elevated N-terminal pro-brain natriuretic peptide, and/or peak oxygen consumption in lowest quartile (according to published norms for TGA patients). Comparative statistics and univariate correlations were performed. Results Eighty-seven patients were included (mean age 39 years; 69% male; 25% ccTGA, 68% NYHA class I) from which one third (29/87) had HF. Most inflammatory markers were significantly higher in the HF group compared to non-HF: CRP (4.3 vs 2.21 mg/dL; P=0.016), RDW (13.6 vs 12.7 fL; P&amp;lt;0.001), NLR (3.6 vs 2.9; P=0.01), MPO (171 vs 139 ng/mL; P=0.03) and MPO-DNA (1.4 vs 1.2; P=0.04). When assessing systolic function, HF patients had: i) lower strain of the sRV free wall (10.9 vs 13.1%; P=0.008), ii) lower mitral annular plane systolic excursion (MAPSE) (1.7 vs 2.1 cm; P&amp;lt;0.001) and iii) lower strain rate (SR) of the subpulmonary LV (spLV) (1.0 vs 1.3 S-1; P=0.03). The spLV was also more hypertrophied (end-diastolic LV posterior wall 0.99 vs 0.79 cm; P=0.007) and more dilated (end-diastolic LV internal diameter 4.1 vs 3.3 cm; P=0.006) in HF. CRP and RDW showed the strongest correlations (Spearman correlation coefficient r&amp;gt;0.29) with LV and RV ventricular function. CRP correlated with lateral tricuspid annular systolic velocity (r=−0.313**), strain of the free wall (r=−0.317**) and global longitudinal strain (r=−0.292**) of the sRV. RDW correlated with MAPSE (r=−0.313**). **P&amp;lt;0.01. Conclusions sRV patients in HF have more systemic inflammation and lower RV free wall strain. With more remodeling and a lower MAPSE and SR of the spLV, the LV cannot be ignored when evaluating HF in sRV patients. Correlation between inflammation and ventricular systolic function, however, is limited. Funding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): ERA-CVD JTC2019 (Fonds Wetenschappelijk Onderzoek G0G1719N to K.M. and A.V.D.B); German Bundesministerium für Bildung und Forschung 01KL2001 to T.W.)

Prognostic factors associated with left ventricular non-compaction: A PRISMA-compliant meta-analysis.

Background:Left ventricular non-compaction (LVNC) is a rare disease with a poor prognosis. Efforts to improve prognosis are limited by the quality and scope of the available evidence on prognostic factors.Methods:Pubmed, Embase, China National Knowledge Infrastructure, Cochrane Library, Wanfang, and Baidu Scholar were searched and all relevant studies that examined factors related to LVNC prognosis, published before January 2021, were retrieved. Study quality evaluation and data extraction were independently completed by two authors. Statistical analyses were performed using STATA 15.0 software.Results:A total of 20 cohort studies were included in this study, with a total of 1910 patients. The results of the meta-analysis are as follows: New York Heart Function Association (NYHA) class III/IV (hazard ratio [HR] = 3.93, 95% confidence interval [CI]: 1.66–9.29), (NT-proBNP) increased (HR = 1.98, 95% CI: 1.10–3.58), left ventricular ejection fraction (LVEF) decreased (HR = 1.04, 95% CI: 1.03–1.06), left ventricular end-diastolic diameter (LVEDD) increased (HR = 1.03, 95% CI: 1.01–1.06) was an independent poor prognostic factor, and body mass index (HR = 0.80, 95% CI: 0.64–0.98) was an independent protective factor. Creatinine (CR) level (HR = 1.09, 95% CI: 0.95–1.25) and late gadolinium-enhanced (LGE) imaging (HR = 3.1, 95% CI: 0.85–11.31) has no statistical significance in the prognosis of LVNC.Conclusion:In LVNC patients, NYHA class III/IV, elevated N-terminal pro-brain natriuretic peptide (NT-proBNP) levels, decreased LVEF, and increased LVEDD may lead to poor prognosis, and increased body mass index may improve the prognosis of LVNC. Further clinical research with large sample sizes and long-term follow-ups should be conducted.PROSPERO Registration Number:42020152706

EP News: Clinical

Parkash et al (Circulation 2022;145:1693, PMID 35313733) conducted a multicenter, open-label trial randomizing patients with paroxysmal (>4 episodes in 6 months) or persistent (duration <3 years) AF, New York Heart Association class II-III heart failure (HF), and elevated N-terminal pro-brain natriuretic peptide (NT-proBNP) to ablation-based rhythm control or rate control. The primary outcome was a composite of all-cause mortality and all HF events. Secondary outcomes included left ventricular ejection fraction (LVEF), 6-minute walk test, and NT-proBNP. Overall, 411 patients were randomized to ablation (n = 214) or rate control (n = 197). The primary outcome occurred in 50 patients (23.4%) in the ablation group and 64 patients (32.5%) in the rate control group (hazard ratio 0.71; P = .066). LVEF increased in the ablation group (10.1% ± 1.2% vs 3.8% ± 1.2%; P = .017); 6-minute walk distance improved (44.9 ± 9.1 m vs 27.5 ± 9.7 m; P = .025) and NT-proBNP decreased (−77.1% vs −39.2%; P < .0001). Adverse events were observed in 50% of patients in both groups. The authors conclude that there was no statistical difference in all-cause mortality or HF events with ablation-based rhythm control vs rate control. There was a nonsignificant trend for improved outcomes with ablation-based rhythm control over rate control.