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      Utility of NT-proBNP as a rule-out test for left ventricular dysfunction in very old people with limiting dyspnoea: the Newcastle 85+ Study

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          Abstract

          Background

          Guidelines advocate using B-type natriuretic peptides in the diagnostic work-up of suspected heart failure (HF). Their main role is to limit echocardiography rates by ruling out HF/LV dysfunction where peptide level is low. Recommended rule-out cut points vary between guidelines. The utility of B-type natriuretic peptides in the very old (85+) requires further investigation, with optimal cut points yet to be established. We examined NT-proBNP's utility, alone and in combination with history of myocardial infarction (MI), as a rule-out test for LV dysfunction in very old people with limiting dyspnoea.

          Methods

          Design: Cross-sectional analysis.

          Setting: Population-based sample; North-East England.

          Participants: 155 people (aged 87-89) with limiting dyspnoea.

          Measures: Dyspnoea assessed by questionnaire. Domiciliary echocardiography performed; LV systolic/diastolic function graded. NT-proBNP measured (Roche Diagnostics). Receiver operating characteristic analyses examined NT-proBNP's diagnostic accuracy for LV dysfunction.

          Results

          AUC for LVEF less than or equal to 50% was poor (0.58, 95% CI 0.49-0.65), but good for LVEF less than or equal to 40% (0.80, 95% CI 0.73-0.86). At ESC cut point (125ng/l), few cases of systolic dysfunction were missed (NPV 94-100%, depending on severity), but echocardiography (88%) and false positive rates (56-81 per 100 screened) were high. At NICE cut point (400ng/l), echocardiography (51%) and false positive rates (33-45) were lower; exclusionary performance was good for LVEF less than or equal to 40% (1 case missed per 100 screened, 15% of cases; NPV 97%), but poor for LVEF less than or equal to 50% (16 cases missed per 100 screened, 45% of cases; NPV 68%). Incorporating isolated moderate/severe diastolic dysfunction into target condition increased the proportion of cases missed (lower NPV), whilst improving case detection. Incorporating MI history as an additional referral prompt slightly reduced the number of cases missed at expense of higher echocardiography and false positive rates.

          Conclusions

          High echocardiography rates and poor exclusionary performance for mild degrees of systolic dysfunction and for diastolic dysfunction limit NT-proBNP's utility as a rule-out test for LV dysfunction in very old people with limiting dyspnoea. Incorporating MI history as an additional echocardiography prompt yields no overall benefit compared to using NT-proBNP level alone.

          Electronic supplementary material

          The online version of this article (doi:10.1186/1471-2261-14-128) contains supplementary material, which is available to authorized users.

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          Most cited references27

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          Natural history of asymptomatic left ventricular systolic dysfunction in the community.

          Information is limited regarding the rates of progression to congestive heart failure (CHF) and death in individuals with asymptomatic left ventricular systolic dysfunction (ALVD). We sought to characterize the natural history of ALVD, by studying unselected individuals with this condition in the community. We studied 4257 participants (1860 men) from the Framingham Study who underwent routine echocardiography. The prevalence of ALVD (visually estimated ejection fraction [EF] 50%, n=4128) and ALVD (n=129) were 0.7 and 5.8 per 100 person-years, respectively. After adjustment for cardiovascular disease risk factors, ALVD was associated with a hazards ratio (HR) for CHF of 4.7 (95% CI 2.7 to 8.1), compared with individuals without ALVD. An elevated risk of CHF after ALVD was observed even in individuals without prior myocardial infarction or valvular disease, with an adjusted HR of 6.5 (CI 3.1 to 13.5). Mild ALVD (EF 40% to 50%, n=78) and moderate-to-severe ALVD (EF <40%, n=51) were associated with adjusted HRs for CHF of 3.3 (CI 1.7 to 6.6) and 7.8 (CI 3.9 to 15.6), respectively. ALVD was also associated with an increased mortality risk (adjusted HR 1.6, CI 1.1 to 2.4). The median survival of ALVD subjects was 7.1 years. Individuals with ALVD in the community are at high risk of CHF and death, even when only mild impairment of EF is present. Additional studies are needed to define optimal therapy for mild ALVD.
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            Systematic review and individual patient data meta-analysis of diagnosis of heart failure, with modelling of implications of different diagnostic strategies in primary care.

            To assess the accuracy in diagnosing heart failure of clinical features and potential primary care investigations, and to perform a decision analysis to test the impact of plausible diagnostic strategies on costs and diagnostic yield in the UK health-care setting. MEDLINE and CINAHL were searched from inception to 7 July 2006. 'Grey literature' databases and conference proceedings were searched and authors of relevant studies contacted for data that could not be extracted from the published papers. A systematic review of the clinical evidence was carried out according to standard methods. Individual patient data (IPD) analysis was performed on nine studies, and a logistic regression model to predict heart failure was developed on one of the data sets and validated on the other data sets. Cost-effectiveness modelling was based on a decision tree that compared different plausible investigation strategies. Dyspnoea was the only symptom or sign with high sensitivity (89%), but it had poor specificity (51%). Clinical features with relatively high specificity included history of myocardial infarction (89%), orthopnoea (89%), oedema (72%), elevated jugular venous pressure (70%), cardiomegaly (85%), added heart sounds (99%), lung crepitations (81%) and hepatomegaly (97%). However, the sensitivity of these features was low, ranging from 11% (added heart sounds) to 53% (oedema). Electrocardiography (ECG), B-type natriuretic peptides (BNP) and N-terminal pro-B-type natriuretic peptides (NT-proBNP) all had high sensitivities (89%, 93% and 93% respectively). Chest X-ray was moderately specific (76-83%) but insensitive (67-68%). BNP was more accurate than ECG, with a relative diagnostic odds ratio of ECG/BNP of 0.32 (95% CI 0.12-0.87). There was no difference between the diagnostic accuracy of BNP and NT-proBNP. A model based upon simple clinical features and BNP derived from one data set was found to have good validity when applied to other data sets. A model substituting ECG for BNP was less predictive. From this a simple clinical rule was developed: in a patient presenting with symptoms such as breathlessness in whom heart failure is suspected, refer directly to echocardiography if the patient has a history of myocardial infarction or basal crepitations or is a male with ankle oedema; otherwise, carry out a BNP test and refer for echocardiography depending on the results of the test. On the basis of the cost-effectiveness analysis carried out, such a decision rule is likely to be considered cost-effective to the NHS in terms of cost per additional case detected. The cost-effectiveness analysis further suggested that, if likely benefit to the patient in terms of improved life expectancy is taken into account, the optimum strategy would be to refer all patients with symptoms suggestive of heart failure directly for echocardiography. The analysis suggests the need for important changes to the NICE recommendations. First, BNP (or NT-proBNP) should be recommended over ECG and, second, some patients should be referred straight for echocardiography without undergoing any preliminary investigation. Future work should include evaluation of the clinical rule described above in clinical practice.
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              Trends in comorbidity, disability, and polypharmacy in heart failure.

              Comorbidity, disability, and polypharmacy commonly complicate the care of patients with heart failure. These factors can change biological response to therapy, reduce patient ability to adhere to recommendations, and alter patient preference for treatment and outcome. Yet, a comprehensive understanding of the complexity of patients with heart failure is lacking. Our objective was to assess trends in demographics, comorbidity, physical function, and medication use in a nationally representative, community-based heart failure population. Using data from the National Health and Nutrition Examination Survey, we analyzed trends across 3 survey periods (1988-1994, 1999-2002, 2003-2008). We identified 1395 participants with self-reported heart failure (n=581 in 1988-1994, n=280 in 1999-2002, n=534 in 2003-2008). The proportion of patients with heart failure who were ≥80 years old increased from 13.3% in 1988-1994 to 22.4% in 2003-2008 (P <.01). The proportion of patients with heart failure who had 5 or more comorbid chronic conditions increased from 42.1% to 58.0% (P <.01). The mean number of prescription medications increased from 4.1 to 6.4 prescriptions (P <.01). The prevalence of disability did not increase but was substantial across all years. The phenotype of patients with heart failure changed substantially over the last 2 decades. Most notably, more recent patients have a higher percentage of very old individuals, and the number of comorbidities and medications increased markedly. Functional disability is prevalent, although it has not changed. These changes suggest a need for new research and practice strategies that accommodate the increasing complexity of this population. Copyright © 2011 Elsevier Inc. All rights reserved.
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                Author and article information

                Contributors
                joanna.collerton@ncl.ac.uk
                andrew.kingston@ncl.ac.uk
                drfyousaf@gmail.com
                karen.davies@ncl.ac.uk
                antoinette.kenny@nuth.nhs.uk
                dermot.neely@nuth.nhs.uk
                carmen.martin-ruiz@ncl.ac.uk
                guy.macgowan@ncl.ac.uk
                a.l.robinson@ncl.ac.uk
                tom.kirkwood@ncl.ac.uk
                bernard.keavney@manchester.ac.uk
                Journal
                BMC Cardiovasc Disord
                BMC Cardiovasc Disord
                BMC Cardiovascular Disorders
                BioMed Central (London )
                1471-2261
                26 September 2014
                26 September 2014
                2014
                : 14
                : 1
                : 128
                Affiliations
                [ ]Institute for Ageing and Health, Newcastle University, Newcastle upon Tyne, UK
                [ ]Department of Cardiology, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK
                [ ]Department of Clinical Biochemistry, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK
                [ ]Institute of Genetic Medicine, Newcastle University, Newcastle upon Tyne, UK
                [ ]Institute of Health and Society, Newcastle University, Newcastle upon Tyne, UK
                [ ]Institute of Cardiovascular Sciences, The University of Manchester, Manchester, UK
                Article
                774
                10.1186/1471-2261-14-128
                4189162
                25257704
                5e052f88-4249-432c-9a63-8437c339d19b
                © Collerton et al.; licensee BioMed Central Ltd. 2014

                This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                History
                : 17 June 2014
                : 18 September 2014
                Categories
                Research Article
                Custom metadata
                © The Author(s) 2014

                Cardiovascular Medicine
                systolic dysfunction,diastolic dysfunction,natriuretic peptides,sensitivity and specificity,aged, 80 and over

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