Pathophysiology of heart failure with preserved ejection fraction

Abstract

Heart failure (HF) is a clinical syndrome causing impaired cardiac performance at rest or during stress. Heart failure with preserved ejection fraction (HFpEF) is a growing health problem associated with high mortality and morbidity. It is a complex multifactorial systemic syndrome with risk factors and mechanisms developing into long term clinical manifestations. HFpEF accounts for half of all HF patients, and boasts similar re-hospitalization and mortality as HF with reduced ejection fraction (HFrEF). The current knowledge about the pathophysiology of HFpEF is growing with new research methodologies to understand its complexities. Examination of the determinants of cardiovascular performance during exercise in HFpEF may reveal novel pathophysiological mechanisms specific to HFpEF phenotype. The overall aim of the thesis is to improve the understanding of pathophysiology of HFpEF. This aim was achieved by following objectives: i) provide evidence for use of a novel-technological advance for evaluation of cardiac function at rest and during stress; ii) define differences in cardiac response to pharmacological and physiological stress between HFpEF, HFrEF and controls, iii) define cardiac adaptations to a novel, personalized, home-based physical activity intervention in HFpEF. The major findings of this thesis suggest: i) bioreactance and two-dimensional transthoracic echocardiography do not show acceptable levels of agreement for estimating cardiac output and cannot be used interchangeably due to disparity in results at rest and after pharmacological stress; ii) HF patients show reduced LV global longitudinal and left atrial reservoir strains, more pronounced in HFrEF than HFpEF at rest and exercise. Left atrial reservoir strain plays an important role responsible for exercise intolerance seen in HFpEF patients; iii) HFpEF and HFpEF patients exhibit different haemodynamic responses to dobutamine stress echocardiography and iv) Active-at-Home-HF intervention is acceptable, safe and feasible in HFpEF patients and helps in increasing daily physical activity levels and improving quality of life.