Table 2.

Comorbidities, causes and cellular, structural and functional remodelling of the heart in HFrEF and HFpEF patients

Co-morbidities and causes	Vascular changes	Cellular changes in the heart	Structural remodelling	Cardiac dysfunction
HFrEF
Hypertension Hypercholesteraemia Diabetes Obesity	Coronary artery disease and ischaemia	Cell death Reduced cardiomyocyte contractility Altered metabolism Altered extracellular matrix Fibrosis Altered beta-adrenergic receptor pathway	Eccentric remodelling (dilated, thin-walled ventricle)	Reduced end-systolic pressure-volume relation Reduced response to exercise Neurohumoral activation
Cardiotoxic agents Viral myocarditis Peripartum cardiomyopathy Genetic defects
HFpEF
Multiple comorbidities: hypertension, obesity, diabetes mellitus, coronary artery disease, sleep apnoea, and lung disease	Proposed: Systemic inflammation-mediated endothelial dysfunction	Stiff cardiomyocytes, i.e. high titin-based passive force Altered extracellular matrix Fibrosis Disturbed nitric oxide signalling	Concentric remodelling (thick-walled ventricle) Atrial dilation	Large patient heterogeneity Abnormal heart compliance and relaxation Elevated left ventricular filling pressure