Table 2

Comparison between HFrEF and HFpEF

Variable/ref	HFrEF	HFpEF
LVEF Ponikowski et al 67	<40%	≥50%
Risk factors Mentz et al 68 Metra and Teerlink69	Male gender Smoking Hypercholesterolaemia Hypertension Diabetes Obesity A familial history of heart failure A predisposition to cardiomyopathies Exposure to cardiotoxic agents	Age Female gender Hypertension Diabetes Obesity Renal dysfunction Chronic obstructive pulmonary disease Anaemia
Organ level Katz and Rolett70	Eccentric LV remodelling	Concentric LV remodelling
Cardiomyocyte level van Heerebeek et al 71	Long and thin cardiomyocyte Reduced myofibrillar density	Short and fat cardiomyocyte Collagen deposition
Molecular level Bers24 Studer et al 26 van Heerebeek et al 71 Hamdani et al 72 Tanaka et al 73 Mishra et al 74	Decreased SERCA2a activity Increased NCX activity Increased SR Ca²⁺ leak Titin shift to compliant N2BA isoform	Decreased SERCA2a activity Reduced NCX activity Increased SR Ca²⁺ leak Titin shift to stiff N2B isoform Titin hypophosphorylation
Pathophysiology Metra and Teerlink69 Paulus and Tschöpe 75 Ferrari et al 76	Neurohormonal activation	One hypothesis is myocardial microvascular inflammatory endothelial activation (remains highly debated)

HFpEF, heart failure with preserved ejection fraction; HFrEF, heart failure with reduced ejection fraction; LV, left ventricular; LVEF, left ventricular ejection fraction; NCX, Na⁺/Ca²⁺ exchange; SERCA2a, sarcoplasmic/endoplasmic reticulum calcium ATPase 2a; SR, sarcoplasmic reticulum.