The multidimensional value of natriuretic peptides in heart failure, integrating laboratory and clinical aspects.

Natriuretic peptides (NP) play an essential role in heart failure (HF) regulation, and their measurement has improved diagnostic and prognostic accuracy. Clinical symptoms and objective measurements, such as NP levels, should be included in the HF definition to render it more reliable and consistent among observers, hospitals, and healthcare systems. BNP and NT-proBNP are reasonable surrogates for cardiac disease, and their measurement is critical to early diagnosis and risk stratification of HF patients. NPs should be measured in all patients presenting with dyspnea or other symptoms suggestive of HF to facilitate early diagnosis and risk stratification. Both BNP and NT-proBNP are currently used for guided HF management and display comparable diagnostic and prognostic accuracy. Standardized cutoffs for each NP assay are essential for data comparison. The value of NP testing is recognized at various levels, including patient empowerment and education, analytical and operational issues, clinical HF management, and cost-effectiveness.

Type 2 Myocardial Infarction: Evolving Approaches to Diagnosis and Risk-Stratification.

BACKGROUND: Type 2 myocardial infarction (T2MI) is frequently encountered in clinical practice and associated with adverse outcomes. CONTENT: T2MI occurs most frequently due to noncoronary etiologies that alter myocardial oxygen supply and/or demand. The diagnosis of T2MI is often confused with acute nonischemic myocardial injury, in part because of difficulties in delineating the nature of symptoms and misunderstandings about disease categorization. The use of objective features of myocardial ischemia using electrocardiographic (ECG) or imaging abnormalities may facilitate more precise T2MI diagnosis. High-sensitivity cardiac troponin (hs-cTn) assays allow rapid MI diagnosis and risk stratification, yet neither maximum nor delta values facilitate differentiation of T2MI from T1MI. Several investigational biomarkers have been evaluated for T2MI, but none have robust data. There is interest in evaluating risk profiles among patients with T2MI. Clinically, the magnitude of maximum and delta cTn values as well as the presence and magnitude of ischemia on ECG or imaging is used to indicate disease severity. Scoring systems such as GRACE, TIMI, and TARRACO have been evaluated, but all have limited to modest performance, with substantial variation in time intervals used for risk-assessment and endpoints used. SUMMARY: The diagnosis of T2MI requires biomarker evidence of acute myocardial injury and clear clinical evidence of acute myocardial ischemia without atherothrombosis. T2MIs are most often caused by noncoronary etiologies that alter myocardial oxygen supply and/or demand. They are increasingly encountered in clinical practice and associated with poor short- and long-term outcomes. Clinicians require novel biomarker or imaging approaches to facilitate diagnosis and risk-stratification.

[Biomarkers in cardio-oncology patients]. / Biomarker bei onkokardiologischen Patienten.

In recent decades, major advances in the treatment of malignant diseases have significantly improved long-term survival. However, this has increased the spectrum of side effects of these treatment methods, particularly for the cardiovascular system. Cardiotoxicity can be acute and chronic, including hypertension, heart failure, arrhythmias, acute myocardial infarction, venous thromboembolism, stroke, and valvular heart disease. While the occurrence of cardiotoxicity is known for many older cancer therapies, it needs to be largely evaluated for newer forms of therapy. Diagnosing possible cardiotoxic side effects is essential for optimal treatment, but remains a challenge. Troponin and the natriuretic peptides play an essential role as cardiac biomarkers in the diagnosis of conventional heart diseases. However, they also appear to play an important role in the detection of cardiotoxicity, as well as in the treatment of cardio-oncology patients. Elevated troponin or B-type natriuretic peptide (BNP)/N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels are associated with increased overall mortality and were associated with the development of heart failure in selected cohorts. Troponin can also be used to identify myocarditis associated with immune checkpoint inhibitor therapy. This overview summarizes the current knowledge about biomarkers for the detection of cardiotoxicity due to tumor therapy. Possible clinical recommendations for the detection of cardiotoxic effects using biomarkers are also outlined.

Incidence and determinants of high-sensitivity troponin and natriuretic peptides elevation at admission in hospitalized COVID-19 pneumonia patients.

BACKGROUND: Myocardial involvement in the course of coronavirus disease 2019 (COVID-19) pneumonia has been reported, though not fully characterized yet. The aim of the present study is to undertake a joint evaluation of hs-Troponin and natriuretic peptides (NP) in patients hospitalized for COVID-19 pneumonia. METHODS: In this multicenter observational study, we analyzed data from n = 111 patients. Cardiac biomarkers subgroups were identified according to values beyond reference range. RESULTS: Increased hs-Troponin and NP were found in 38 and 56% of the cases, respectively. As compared to those with normal cardiac biomarkers, these patients were older, had higher prevalence of cardiovascular diseases (CVD) and had more severe COVID-19 pneumonia by higher CRP and D-dimer and lower PaO2/FIO2. Two-dimensional echocardiography performed in a subset of patients (n = 24) showed significantly reduced left ventricular ejection fraction in patients with elevated NP (p = 0.02), whereas right ventricular systolic function (tricuspid annular plane systolic excursion) was significantly reduced both in patients with high hs-Troponin and NP (p = 0.022 and p = 0.03, respectively). Both hs-Troponin and NP were higher in patients with in-hospital mortality (p = 0.001 and p = 0.002, respectively). On multivariable analysis, independent associations were found of hs-Troponin with age, PaO2/FIO2 and D-dimer (B = 0.419, p = 0.001; B = - 0.212, p = 0.013; and B = 0.179, p = 0.037, respectively) and of NP with age and previous CVD (B = 0.480, p < 0.001; and B = 0.253, p = 0.001, respectively). CONCLUSIONS: Myocardial involvement at admission is common in COVID-19 pneumonia. Independent associations of hs-Troponin with markers of disease severity and of NP with underlying CVD might point toward existing different mechanisms leading to their elevation in this setting.

Natriuretic Peptides as a Prognostic Marker for Delirium in Cardiac Surgery-A Pilot Study.

Background and Objectives: Delirium is a common and major complication subsequent to cardiac surgery. Despite scientific efforts, there are no parameters which reliably predict postoperative delirium. In delirium pathology, natriuretic peptides (NPs) interfere with the blood-brain barrier and thus promote delirium. Therefore, we aimed to assess whether NPs may predict postoperative delirium and long-term outcomes. Materials and Methods: To evaluate the predictive value of NPs for delirium we retrospectively analyzed data from a prospective, randomized study for serum levels of atrial natriuretic peptide (ANP) and the precursor of C-type natriuretic peptide (NT-proCNP) in patients undergoing coronary artery bypass grafting (CABG) with or without cardiopulmonary bypass (off-pump coronary bypass grafting; OPCAB). Delirium was assessed by a validated chart-based method. Long-term outcomes were assessed 10 years after surgery by a telephone interview. Results: The overall incidence of delirium in the total cohort was 48% regardless of the surgical approach (CABG vs. OPCAB). Serum ANP levels >64.6 pg/mL predicted delirium with a sensitivity (95% confidence interval) of 100% (75.3-100) and specificity of 42.9% (17.7-71.1). Serum NT-proCNP levels >1.7 pg/mL predicted delirium with a sensitivity (95% confidence interval) of 92.3% (64.0-99.8) and specificity of 42.9% (17.7-71.1). Both NPs could not predict postoperative survival or long-term cognitive decline. Conclusions: We found a positive correlation between delirium and preoperative plasma levels of ANP and NT-proCNP. A well-powered and prospective study might identify NPs as biomarkers indicating the risk of delirium and postoperative cognitive decline in patients at risk for postoperative delirium.

The role of natriuretic peptide estimation in severe COVID-19.

Since its inception in Wuhan in December 2019, Coronavirus disease 2019 (COVID-19) has shattered the economies and health-care infrastructures worldwide. Even the best of health-care systems (United States, Italy) have been overwhelmed and collapsed because of this unprecedented pandemic. India is preparing itself for the onslaught of Coronavirus. After recording its first case on January 30th, 2020, the rise was slow until the last week of March. However, since then, the number of cases has increased exponentially, and as on April 14th, 2020, there have been more than 10,000 cases of coronavirus disease (COVID-19) in India, which has resulted in more than 350 deaths.

The Biomarkers for Acute Myocardial Infarction and Heart Failure.

The use of a large number of cardiovascular biomarkers, meant to complement the use of the electrocardiogram, echocardiography cardiac imaging, and clinical symptom assessment, has become a routine in clinical diagnosis, differential diagnosis, risk stratification, and prognosis and guides the management of patients with suspected cardiovascular diseases. There is a broad consensus that cardiac troponin and natriuretic peptides are the preferred biomarkers in clinical practice for the diagnosis of the acute coronary syndrome and heart failure, respectively, while the roles and possible clinical applications of several other potential biomarkers are still under study. This review mainly focuses on the recent studies of the roles and clinical applications of troponin and natriuretic peptides, which seem to be the best-validated markers in distinguishing and predicting the future cardiac events of patients with suspected cardiovascular diseases. Additionally, the review briefly discusses some of the large number of potential markers that may play a more prominent role in the future.

A value proposition for natriuretic peptide measurement in the assessment of patients with suspected acute heart failure.

There is robust clinical trial evidence supporting the role of natriuretic peptides [NPs] in the assessment of patients presenting with suspected acute heart failure [AHF]. Despite the fact that clinical guidelines have for some time advocated NP measurement, the availability and uptake of NP testing in acute care services remains patchy and incomplete. The reasons for this are multifactorial but are underpinned by compartmentalised management and budget structures within complex healthcare delivery organisations. This paper outlines a value proposition for NP testing in the acute care setting which crosses the continuum of services and budgets. It articulates the expected benefits to each stakeholder in terms of efficiency of processes, clinical outcomes and cost effectiveness. It describes a pathway to implementation and suggests metrics that may be used to measure the effectiveness of introduction of NP testing. It is hoped that the value proposition will facilitate the uptake of NT testing fostering collaboration between laboratory, clinical, management and finance teams and by informing the development of business cases.

La congestión residual y la intuición clínica en la insuficiencia cardiaca descompensada / Residual congestion and clinical intuition in decompensated heart failure

Los síntomas congestivos son la clave para reconocer las descompensaciones de la insuficiencia cardiaca. Su tratamiento se basa en la reducción de la congestión hasta alcanzar una situación clínica que permita el alta del paciente para continuar el tratamiento ambulatoriamente. Lo importante, no obstante, no es el grado de congestión al ingreso, sino la que persiste después de un tratamiento diurético enérgico. A la persistencia de signos congestivos después de un tratamiento aparentemente correcto y eficaz, se le ha denominado «congestión residual» y se asocia con mal pronóstico. Las herramientas para su estimación son todavía rudimentarias, por lo que deben desarrollarse métodos que permitan una valoración más precisa

Congestive symptoms are the key to recognising decompensated heart failure, whose treatment is based on reducing the congestion until a clinical situation has been reached that allows the patient to be discharged to continue outpatient treatment. The important aspect is not the degree of congestion at admission but rather the congestion that persists after energetic diuretic therapy. The persistence of congestive signs following an apparently correct and effective therapy has been called residual congestion and is associated with a poor prognosis. The tools for determining this condition are still rudimentary. Methods therefore need to be developed that enable a more accurate assessment

Biomarkers in Atrial Fibrillation and Heart Failure.

Atrial fibrillation (AF) is the most common sustained arrhythmia encountered in clinical practice and an important contributor to cardiovascular morbidity and mortality. Although the exact mechanisms behind AF are not completely elucidated, the underlying pathophysiological changes have been well described. Predisposal factors for AF include the older age, the increased left atrial size, the decreased left atrial function, the presence of heart failure and left ventricular systolic dysfunction and the presence of coronary heart disease or pulmonary or mitral valve disease. In addition to these factors, emerging evidence demonstrate that myocardial strain, fibrosis and inflammation, are associated with AF as well as the pathogenesis of the arrhythmia. The natruretic peptide system including Atrial Natriuretic Peptide (ANP), Brain Natriuretic Peptide (BNP) and C-type Natriuretic Peptide (CNP) is indicative of the level of myocardial strain which may predispose to AF. As a result, the aforementioned peptides are increased in AF patients. The levels of myocardial fibrosis biomarkers, such as ST2 and Galectin-3, are elevated suggesting atrial structural abnormalities, while the increased levels of CRP and Interleukin-6 supplement the inflammatory profile of AF patients. Emerging data for the aforementioned biomarkers are discussed in the present review.

Biomarkers in Aortic Valve Stenosis and their Clinical Significance in Transcatheter Aortic Valve Implantation.

Aortic valve stenosis is one of the most common valvular heart disorders and the prevalence will rise as the population ages. Once symptomatic patients with aortic valve stenosis tend to fare worse with high mortality rates. Aortic valve replacement is indicated in these patients and besides the standard surgical replacement, a less invasive approach, transcatheter aortic valve implantation, has gained momentum and has showed promising and solid results in patients with high surgical risk. An important aspect of evaluating patients with aortic valve stenosis is the ability to choose the best possible candidate for the procedure. In addition, predicting the short and long-term clinical outcomes after the valve replacement could offer the treating physicians a better insight and provide information for optimal therapy. Biomarkers are biological parameters that can be objectively measured and evaluated as indicators of normal biological processes and are easily monitored. The aim of this review is to critically assess some of the most widely used biomarkers at present (natriuretic peptides, troponins, C-reactive protein) and provide an insight in novel biomarkers that are currently being investigated (galectin-3, growth differentiation factor-15, microRNAs) for possible diagnostic and prognostic use in aortic valve stenosis and transcatheter aortic valve implantation respectively.

Biomarkers Determining Prognosis of Atrial Fibrillation Ablation.

Catheter ablation for rhythm control is recommended in specific patient populations with paroxysmal, persistent, or long-standing persistent atrial fibrillation. Pulmonary vein isolation is the cornerstone of the ablative therapy for atrial fibrillation. However, relapse is still common since the single procedure efficacy of atrial fibrillation ablation was estimated to be 60-80% in paroxysmal and 50-70% in persistent atrial fibrillation. It is important to identify predictors of successful atrial fibrillation patients ablation. In the present review, we will assess the role of available biomarkers to predict responders of an initial atrial fibrillation catheter ablation. Emphasis has been given on the role of myocardial injury biomarkers, natriuretic peptides and traditional inflammatory markers. Novel inflammatory markers, oxidative stress biomarkers and microRNAs have also been examined as predictors of a successful atrial fibrillation procedure. Notably, the impact of procedural and short-term administration of steroids, as well as the role of colchicine on preventing atrial fibrillation recurrence after ablation is thoroughly presented.

Amniotic Fluid Natriuretic Peptide Levels in Fetuses With Congenital Heart Defects or Arrhythmias.

BACKGROUND: We have previously demonstrated that umbilical cord plasma natriuretic peptide (NP) levels reflect the severity of heart failure (HF) in fetuses with congenital heart defects (CHD). The aim of this study was to evaluate the significance of amniotic fluid (AF) NP levels in the assessment of HF in fetuses with CHD or arrhythmia. Methods and Results: This was a prospective observational study at a tertiary pediatric cardiac center. A total of 95 singletons with CHD or arrhythmia, and 96 controls from 2012 to 2015 were analyzed. AF concentrations of atrial NP (ANP), B-type NP (BNP) and N-terminal pro-B-type NP (NT-proBNP) at birth were compared with ultrasonographic assessment of fetal HF using the cardiovascular profile (CVP) score. Multivariate analysis showed that a CVP score ≤5 and preterm birth are independently associated with high AF NT-proBNP levels. AF NT-proBNP levels of fetuses with CHD or arrhythmia inversely correlated with CVP score (P for trend <0.01). In contrast, AF concentrations of ANP and BNP were extremely low, and it was difficult to assess the degree of fetal HF based on them. CONCLUSIONS: AF NT-proBNP concentrations increase in stepwise fashion with the severity of HF in fetuses with CHD or arrhythmia; it was the optimal NP for assessing the fetal HF.

Selección de lo mejor del año 2017 en insuficiencia cardiaca aguda y crónica / Selection of the best of 2017 in acute and chronic heart failure

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Selección de lo mejor del año 2017 en insuficiencia cardiaca del paciente anciano / Selection of the best of 2017 in heart failure in elderly patients

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Avaliação dos níveis plasmáticos do peptídeo natriurético NT-proBNP em cães da raça Poodle em diferentes estágios da doença valvar crônica mitral / Evaluation of plasma levels of NT-proBNP natriuretic peptide in Poodle dogs at different stages of chronic mitral valve disease

A doença valvar crônica mitral (DVCM) é comum em cães e pode não causar sintomas clínicos da insuficiência cardíaca (IC) durante anos. O peptídeo natriurético tipo B (BNP) é armazenado nos miócitos ventriculares e secretado para circulação com seu fragmento NT-proBNP, quando ocorre aumento. Este estudo avaliou os níveis plasmáticos do peptídeo natriurético NT-proBNP em cães da raça Poodle em diferentes estágios da DVCM, seguindo as diretrizes do American College of Veterinary Internal Medicine (ACVIM, 2009). Amostras de sangue foram coletadas para determinação do biomarcador NT-proBNP para comparação entre grupos. As medianas do NT-proBNP nos grupos estudados foram: 551pmol/L (controle), 302pmol/L (grupo B1), 1.033pmol/L (grupo B2), 954pmol/L (grupo C) e 5.541pmol/L (grupo D). Mediante o uso de um ponto de corte ideal de >709pmol/L, foi possível identificar os cães com aumento cardíaco verdadeiro daqueles sem aumento cardíaco, com sensibilidade de 75% e especificidade de 100%. O NT-proBNP aumentou de acordo com o avanço dos estágios da DVCM, sendo os estágios B2, C e D aqueles com valores mais elevados desse biomarcador. Para o estágio B2, a mensuração do NT-proBNP mostrou ser uma excelente ferramenta para diagnosticar precocemente o aumento cardíaco em cães da raça Poodle.(AU)

Chronic mitral valve disease (CMVD) is common in dogs, it may not cause clinical symptoms of heart failure (HF) for years. The type B natriuretic peptide (BNP) is stored in the ventricular myocytes and secreted for circulation with its NT-proBNP fragment, when an increase occurs. This study evaluated the plasma levels of the NT-proBNP natriuretic peptide in Poodles at different stages of CMVD, following the guidelines of the American College of Veterinary Internal Medicine (ACVIM, 2009). Blood samples were collected for determination of NT-proBNP biomarker for comparison between groups. This median NT-proBNP in the studied groups were: 551pmol/L (Control), 302pmol/L (Group B1), 1,033pmol/L (Group B2), 954pmol/L (Group C) and 5,541pmol/L (Group D). Using an ideal cutoff of > 709pmol/L it was possible to identify dogs with true heart enlargement of those without a cardiac increase with sensitivity of 75% and specificity of 100%. NT-proBNP increased according to the progress of the stages of CMVD, being that stages B2, C and D, with the highest values of the biomarker. To stage B2, the NT-proBNP measurement proved to be an excellent tool for early diagnosis of cardiac enlargement in Poodles.(AU)

Cardiac involvement in Fukuyama muscular dystrophy is less severe than in Duchenne muscular dystrophy.

BACKGROUND: One of the main complications in patients with muscular dystrophies is cardiac dysfunction. The literature on cardiac involvement in patients with Fukuyama congenital muscular dystrophy (FCMD) is limited. AIM: To compare cardiac involvement between patients with FCMD and Duchenne muscular dystrophy (DMD). METHODS: We compared cardiac involvement between 30 patients with FCMD and 181 patients with DMD using echocardiography and serum biomarkers. All patients were receiving regular checkups at Kobe University Hospital. We used single regression analysis to compare echocardiographic parameters, age, and serum biomarkers. RESULTS: Almost all clinical and echocardiographic parameters were lower in patients with FCMD than DMD. The brain natriuretic peptide concentration in patients with FCMD showed no correlation with age or left ventricular ejection fraction (r=0.231, p=0.22 and r=0.058, p=0.76, respectively). A log-rank test revealed that the risk of left ventricular systolic dysfunction was lower in patients with FCMD than DMD (p=0.046, hazard ratio=0.348). CONCLUSION: The clinical progression of cardiac dysfunction is significantly milder in patients with FCMD than DMD, while skeletal muscle involvement is significantly worse in patients with FCMD. These data suggest that the pathophysiological findings of FCMD can be explained by less severe cardiac dysfunction in FCMD than DMD.

Nuevas recomendaciones de las guías europeas de 2016 para el diagnóstico y tratamiento de la insuficiencia cardiaca / New recommendations of 2016 European Guidelines for the diagnosis and treatment of heart failure

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Natriuretic peptides: degradation, circulating forms, dosages and new therapeutic approaches.

Testing for natriuretic peptides (BNP, NT-proBNP or MR-proANP) is recommended by the European Society of Cardiology (ESC) since 2005 for the exclusion diagnosis of acute and chronic heart failure because of very high predictive values. Natriuretic peptides are produced by the heart in response to high transmural pressure and/or myocardial ischemia. These peptides circulate in blood of both healthy subjects and heart failure patients. Mass spectrometry methods allowed identifying a collection of circulating and degraded forms of BNP, NT-proBNP and proBNP. Glycosylated forms of NT-proBNP and proBNP have also been identified. Current immunoassays are lacking analytical specificity due to high cross-reactivities between circulating forms. Moreover, glycosylation has been found to interfere with the capacity of antibodies to bind correctly to analytes. These elements have been taken into account to propose strategies for the development of new standardized and improved immunoassays. More recently, the better understanding of the degradation pathways of natriuretic peptides allowed the raise of new therapeutic approaches for heart failure patients. All these elements are detailed in this review.

Changing concept in treatment of asymptomatic severe aortic stenosis and normal ejection fraction: time for biomarkers reappraisal.

The uncertainty of whether/how to treat asymptomatic patients with isolated severe aortic stenosis and normal left ventricular ejection fraction is one of the most topical in cardiovascular medicine. Recently, the AVATAR trial: first ever randomized trial in the setting of aortic stenosis has been started in an attempt to adequately address this 'burning issue'. In light of this fact it is important to identify biomarkers which might help in risk stratification of these patients, not only in the referring physician's office during a routine exam, but also for preoperative patients scheduled for surgical replacement/transcatheter aortic valve implantation. This report is focusing on novel laboratory parameters which might be helpful in this risk stratification.