Cardiac dysfunction in the very elderly : the relevance of natriuretic peptide testing in clinical practice
(2012)
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- (en) The introduction provides the rationale and aim for this thesis. First, the problem of a forthcoming “grey epidemic” is outlined. In coming decades, this will lead to a heavy burden of chronic diseases and high prevalence of multimorbidity in elderly of our western society. Attention is then focussed on the problem of heart failure in this ageing society. To date, little reliable data on the prevalence and incidence of heart failure are available for Belgium. Furthermore, there is no gold standard for the diagnosis of heart failure. Moreover, the diagnosis of chronic heart failure is often challenging, particularly in the elderly. This emphasises the need for a simple test to identify patients at risk. Natriuretic peptides have been suggested as the ‘ultimate’ biochemical test for heart failure. However, whether this is also true in complex geriatric subjects remains to discover. Therefore, this thesis sets out to unravel unsolved issues about the implementation of natriuretic peptides in routine clinical practice for the diagnosis of severe cardiac dysfunction in the oldest old. In Chapter 1 we investigated whether natriuretic peptides remained a specific marker of cardiac illness and were able to predict all cause and cause specific mortality in a population-based cohort of nonagenarians from the Leiden 85-plus Study. The median follow-up for the 274 90-year-old participants was 42.3 months. We found levels of NT-proBNP increased significantly with increasing numbers of cardiac diagnoses. High NT-proBNP levels were associated with overall mortality, cardiovascular mortality and non-cardiovascular mortality, both in participants with and without specific cardiac diagnoses. The latter meaning in participants without known cardiac morbidity elevated levels of NT-proBNP possibly reflect unknown cardiac morbidity or imminent heart failure. We concluded NT-proBNP remains a disease specific marker of cardiac illness in nonagenarians and can possibly be used as a predictor of mortality independent from the presence of known cardiac diagnoses. Chapter 2 presents a systematic review to evaluate the diagnostic accuracy of plasma natriuretic peptide measurement in elderly patients from the general population. Electronic searches of MEDLINE and EMBASE were performed. The quality of the selected studies was assessed with the modified QUADAS tool and the data extracted by two independent reviewers. Five studies with moderate quality were included. The extracted data could not be pooled. To conclude, limited evidence was found supporting the measurement of natriuretic peptides for diagnosis of cardiac dysfunction or heart failure in the elderly of 75 years and over in the general population. Furthermore, important questions about the implementation of plasma natriuretic peptide measurement in daily practice remain unresolved. Chapter 3 studies the relation between NT-proBNP and cardiac abnormalities and evaluates the use of NT-proBNP to exclude structural and functional cardiac abnormalities in a community-based sample of “well-functioning” nonagenarians. Therefore, a diagnostic cross-sectional study embedded within the Leiden 85-plus Study was performed in a convenience sample of 80 nonagenarians. Levels of NT-proBNP were related to a wide variety of echocardiographic abnormalities. A pre-specified cut-off level showed high negative predictive values (NPV) for left ventricular systolic dysfunction, left atrial enlargement, severe valvular heart disease and pulmonary hypertension. The test performance of NT-proBNP to exclude any echocardiographic abnormality showed a moderately high NPV. To conclude, NT-proBNP could be used to exclude echocardiographic abnormalities in well-functioning nonagenarians and might be used to indicate who needs to be referred for further cardiovascular examination. Chapter 4 describes the methodology of the BELFRAIL cohort study (BFC80+). The BFC80+ study is a prospective, observational, population-based cohort study of 567 subjects aged 80 years and older in three well-circumscribed areas of Belgium. The general aim of the BFC80+ study is to examine the dynamic interaction between health, frailty and disability in a multi-system approach focusing on cardiac dysfunction and chronic heart failure, lung function, sarcopenia, renal insufficiency and immunosenescence. Only three exclusion criteria were used: severe dementia, in palliative care and medical emergency. Two sampling methods for the recruitment of patients were used. Every study participant was invited to undergo four study visits. The general practitioner recorded background variables and medical history and performed a detailed anamnesis and clinical examination. The clinical research assistant performed an extensive examination including performance testing, questionnaires and technical examinations. Echocardiography was performed at home by a cardiologist. A blood sample was collected in the morning. Follow-up reporting of hard outcome measures including mortality, hospitalization and morbidity was organized. A second data collection is planned after 18 months. The wide variety of dimensions investigated in the BFC80+ will enable us not only to investigate in depth the relationship between the different physiological systems but also to initiate new research questions based on this unique database of community-dwelling elderly. In Chapter 5 we sought to describe the prevalence of cardiac dysfunction in the very elderly and to investigate the correlation between echocardiographic abnormalities and indicators of poor functioning. This study was a cross-sectional analysis within the BFC80+ study. Severe cardiac dysfunction was found to be very prevalent and was defined as systolic dysfunction, valvular heart disease or isolated severe diastolic dysfunction. Severe cardiac dysfunction, and more specifically aortic stenosis, showed to be an independent identifier of poor performance, a low LAPAQ (LASA Physical Activity Questionnaire) score and a high GDS-15 (Geriatric Depression Scale) score. Classic indicators of systolic and diastolic dysfunction, however, were not able to identify participants with poor functioning. This study shows the very elderly represent a very heterogeneous group of subjects with a high prevalence of comorbidities, among whom poor functioning might be triggered by multiple causes. We concluded these findings should encourage clinicians not to be blinded by a disease-oriented approach but rather to focus on functional repercussions of cardiac dysfunction and comorbidities in the very elderly. In Chapter 6 we further investigated the hypothesis that natriuretic peptides could be used to identify ‘pancardiac’ damage. Furthermore, the impact of confounders on the association between natriuretic peptide levels and cardiac dysfunction was explored. This study was a diagnostic cross-sectional study embedded within the BFC80+ study. Circulating levels of natriuretic peptides were independently related to several functional and structural echocardiographic parameters, such as aortic stenosis, left atrial volume, left ventricular diameter, E/A, E’ and deceleration time. Adjusting for identified confounders did not improve the diagnostic accuracy of the natriuretic peptides for severe cardiac dysfunction, except in subjects with chronic atrial fibrillation (CAF) or pacemaker (PM). However, stratifying for individual confounders showed that different cut-off values could be used to optimise the diagnostic characteristics of natriuretic peptides. In Chapter 7 a cross-sectional, “intention to diagnose”, analysis within the BFC80+ study was conducted to determine the added diagnostic value of natriuretic peptides and electrocardiograms beyond previous medical history, anamnesis, physical examination and routine laboratory tests for patients with severe cardiac dysfunction. Two analytical tools were used: logistic regression analysis and Classification and Regression Trees (CART) analysis. In patients without CAF or PM, there was only little added value in implementing natriuretic peptides or electrocardiograms for diagnosing severe cardiac dysfunction in daily practice. However, a higher number of participants were correctly classified by integrating natriuretic peptides and electrocardiograms in the diagnostic process. In participants with CAF or PM, the clinical model showed very high accuracy and no added value of natriuretic peptides was found. In the general discussion the main findings that sorted from this thesis are combined and interpreted. First, the framework in which context these results should be interpreted is discussed. The forthcoming grey epidemic and therefore booming of multimorbidity in an ageing society, necessitates a paradigm shift from a disease-oriented approach to more horizontal, comprehensive care. In this regard, the target condition of this thesis was studied within a multi-dimensional approach. The discussion further focusses on the relevance of identifying severe cardiac dysfunction and the use of natriuretic peptides to reach this goal. Furthermore, the implementation of natriuretic peptides in routine clinical practice for the case-finding of severe cardiac dysfunction is discussed. Finally, future research topics within the BFC80+ study are described.
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Citations
Vaes, B. (2012). Cardiac dysfunction in the very elderly : the relevance of natriuretic peptide testing in clinical practice. https://hdl.handle.net/2078.5/156580