Prediction, Prevention and Treatment of Progressing Heart Failure and Coincident Cognitive Impairment

Projektplan - Bakgrund/Målsättning
It has been increasingly recognized that patients who are hospitalized for congestive heart failure (CHF) treatment show signs of cognitive impairment at discharge. About 25% of patients discharged after treatment for heart failure have persisting cognitive impairment, with executive functions, memory, speech and mental processing speed being impaired dominantly. In purpose to find the aetiology for impaired cognitive function the CHF population, several explanations have been proposed; including impaired cerebral vessel reactivity, scattered emboli and cerebral hypoperfusion. A reduction of cerebral perfusion has previously been described as a crucial part in the development of dementia, in the maintenance of quality of life and for the compliance to optimal medical treatment, which is the basis of all evidence–based heart failure treatment.
The major objective of this PhD project is to explore the presumed association between cerebral oxygenation and impaired cognitive function in patients diagnosed with CHF. Untreated or insufficiently treated heart failure and consecutive hypotension lead to cerebral hypoperfusion, which result in cognitive dysfunction. We postulate that there is a state of cardiac dementia that is related to heart failure and that can be prevented and treated.
The Harvest (HeARt and brain failure InVESTtigation Group – HARVEST) research project was first initiated at Heart Failure and Valvular clinic in Skåne University Hospital, Malmö. The purpose for this research project is to explore correlations between Heart Failure and Cognitive dysfunction. The study is approved by the ethical committee in Lund and ongoing (started April 2014)
A large cohort of patients with congestive heart failure (n=2000) will be established and prospectively followed by clinical re–examinations and also through well–validated Swedish national and local registers. Environmental, socioeconomic, and lifestyle factors will be characterized. Phenotypes will be analysed in detail by non–invasive imaging to assess heart function (echocardiographic examination (UCG), cognitive function (cognitive tests, cerebral circulation measurements by cerebral oximetry (cerebral tissue oxygen saturation = SctO2)), as well as hemodynamic response as measured by head–up tilt test (HUTT) combined with SctO2. These data, in combination with an extensive biomarker program and full–scale genomic and metabolomic studies, will give us the potential to reveal new mechanisms and potential therapeutic targets for the treatment of CHF and prevention of coincident cognitive impairment or dementia. Parameters that will be included at all visits are standardized medical history (including medication), clinical examination (e.g. blood pressure, waist circumference, weight, ECG), cognitive testing (MOCA, AQT, cube copying test, Trailmaking A and B, Stroop Test), blood samples according to the clinic's procedures. At baseline we will also collect blood sample collection (fasting) for genomic and metabolomic and biomarker analysis (n=2000) and conduct UCG as well as cerebral oximetry and HUTT (n=500).

Projektplan - Planerade avhandlingsdelar och tidplan
–Study 1
Near–infrared Spectroscopy to Assess Cerebral Perfusion during Head–up Tilt–table Test in adult Patients with syncope within the SYSTEMA Study
Objective: To prospectively explore how the cerebral oxygenation ( SctO2) correlates to hemodynamic parameters during Head–up Tilt –table Test in patients with a history of syncope of unknown origin. To investigate whether Near–infrared Spectroscopy is a feasible method of measurement for cerebral blood perfusion.
In Progress
–Study 2
Objective: To explore how patients diagnosed with CHF react hemodynamically during Head–up Tilt –table Test and to analyse how the cerebral oxygenation is affected. To study whether different grades of heart failure severity are associated to varied cerebral tissue oxygen saturation (SctO2%) levels.
In progress
–Study 3
Objective: To test how (at baseline examination) different cognitive functions (cognitive test results) correlates to SctO2 values and changes in blood pressure and other hemodynamic parameters during Head–up Tilt –table Test. To prospectively follow how the CHF–treatment program at the clinic affects the cognitive functions and cerebral blood flow (as measured by a set of cognitive tests and SctO2), hemodynamic response (as measured by Head–up Tilt –table Test).
–Study 4
Objective: To test for genetic variants metabolites and metabolomic patterns associations with cognitive dysfunction as measured by cognitive tests and cerebral oximetry during Head–up Tilt –table Test.
Timeframe: