Predicting Death in Chronic Heart Failure: Electrocardiographic, Autonomic and Neuroendocrine Risk Assessment

Morley-Davies, Adrian J (2000) Predicting Death in Chronic Heart Failure: Electrocardiographic, Autonomic and Neuroendocrine Risk Assessment. PhD thesis, University of Glasgow.

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Chronic heart failure is a common condition with an adverse prognosis. Despite optimal treatment, ambulant patients with mild symptoms have an annual mortality of more than 15%. Clinical, exercise, echocardiographic and haemodynamic variables are known to carry prognostic information, but accurate identification of those most likely to die remains difficult. This work assessed abnormalities of ventricular activation and repolarisation respectively using the signal-averaged electrocardiogram and interlead QT interval variability of the standard 12-lead electrocardiogram. Disordered autonomic function is common in cardiac failure. This was assessed by 24 hour heart rate variability and baroreflex sensitivity. Plasma noradrenaline and plasma atrial and brain natriuretic peptide levels were used to assess neuroendocrine activation, a hallmark of chronic heart failure. These measures were determined prospectively and compared with known prognostic variables in a chronic heart failure population. Original Hypotheses 1. Sudden cardiac death in patients with heart failure is caused predominantly by malignant ventricular arrhythmias. These may be predicted by non-invasive markers of the arrhythmogenic substrate i.e. signal-averaged ECG, QT dispersion; triggers i.e. non-sustained ventricular tacycardia, and autonomic modulators i.e. heart rate variability and baroreflex sensitivity. This assessment will provide additional independent prognostic information on mortality risk in patients with chronic heart failure. 2. Markers of neuroendocrine activation and autonomic dysfunction would predict progression of chronic heart failure, and all-cause and progressive heart failure death. Discussion Chronic heart failure is a common, growing and major public health care burden. Identifying high-risk patients suitable for aggressive intervention, optimisation of treatment and prevention of death is of great importance. Despite extensive study by many investigators, identification of those patients who are most likely to deteriorate and die remains difficult. In this well-characterised cohort of patients with chronic heart failure, neuroendocrine activation assessed by plasma BNP or plasma Noradrenaline predicted cardiovascular death. This information was additive to and independent of other powerful prognostic variables including NYHA class, age, left ventricular ejection fraction, peak VO2 and presence/absence of bundle branch block. However, plasma BNP may be measured from a simple venous blood sample, and has been proven to be stable at room temperature over 72 hours. It is inexpensive, and requires no specialised equipment at the bedside. Direct assay kits are now available which both simplify and lessen the cost of its measurement. This has implication for its more widespread use. Interestingly, a positive SAECG, the presence of non-sustained ventricular tachycardia and depressed baroreflex sensitivity all identified a patient cohort at high risk of sudden death. Linking this data with the prognostic importance of depressed baroreflex sensitivity in the study cohort with recent data on "electrical storms" in patients with implantable cardioverter-defibrillators, it suggests that these markers might be used to identify patients who would benefit from these devices. (Abstract shortened by ProQuest.).

Item Type: Thesis (PhD)
Qualification Level: Doctoral
Additional Information: Adviser: S M Cobbe
Keywords: Medicine
Date of Award: 2000
Depositing User: Enlighten Team
Unique ID: glathesis:2000-74908
Copyright: Copyright of this thesis is held by the author.
Date Deposited: 13 Nov 2019 15:58
Last Modified: 13 Nov 2019 15:58

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