Heart Failure with Preserved Ejection Fraction (HEFPEF)
diagnosis (Paulus et al 2007)
Data sources
therapies
prevelance
50% of heart failure patients
normal systolic function, > 50% EF and LVEDVI < 97 mL/m^2
symptoms of congestive heart failure (ankle swelling, pulmonary oedema, fatigue, )
LVEDVI is end diastolic volume of left ventricle indexed by body surface area
diastolic dysfunction
invasive EDP > 16 mmHg or pulmonary capillary wedge pressure > 12 mmHg
non-invasive tissue doppler E/E' >15
prognosis Owan et al 2006
Research Questions
How are HEFPEF and HEFREF related?
Mechanics
Reduced LAX function and increased SAX function (Paulus et al 2007)
PV -Loop Phenomena
5 year survival < %40
diastolic stiffness
extracellular matrix
cardiomyocytes
echo
doppler fluid velocities
CMR
Pressure cathers
volume
volume
Can the diagnosis or part of the diagnosis of HEFPEF be automated?
Are there distinct phenotypes with different prognosis and/or traits?
ML 3 distinct phenotypes with differing level of risk (Shat et al 2015)
How can we predict risk or prognosis? #
risk factors
hypertension (Shah et al 2014
)
Poisson Regression, 39 372 patients, lower EF and 13 other predictors of mortality MAGGIC risk score
What can we learn from PV loops?
2/3 patients have abormally high collagen levels Borbely 2005
titin-isoform switching less stiff to more stiff Borlaug 2010
Lack of energy to power crossbridge detachment Borlaug 2010
Elevated End Systolic Elastance Borlaug 2010
diabetes
consequences
exercise intolerance
Lack of cardiac output increase in exercise due to slower heart rates (chronotopic incompetance) and smaller stroke volume Borlaug 2010
In contrast to HFrEF, clinical trials with pharmacological agents show limited success Borlaug 2010
High extracellular volume fraction (diffuse fibrosis) Webb 2018