Table 1|.

Determinants of functional capacity: effects of age and disease

Physiological system	Physiological effects	Age-related effects*	Heart failure-related effects
Central
Cardiovascular	• ↑ Cardiac output • ↑ Heart rate • ↑ Stroke volume	• ↓ Peak cardiac output • ↓ Diastolic performance • ↓ Chronotropic reserve	↓↓ Cardiac output (rest and peak) owing to added pathophysiological impairments of systole and/or diastole, and added reduction in chronotropic reserve
	Enhanced ventricular–vascular coupling	Diminished ventricular–vascular coupling • Ventricular: ↑ collagen, fibrosis, cardiac amyloid, and lipofuscin; ↑ myocardial stiffness and spherical remodelling • Vascular: ↑ intimal–medial thickness with ↓ nitric oxide and ↑ angiotensin II, with ↓ vasodilatory capacity	↑↑ Vascular stiffness owing to disease neurohormonal effects (↑ angiotensin II, ↓ nitric oxide, ↑ noradrenaline), as well as physiological vasoconstriction to maintain haemodynamics as cardiac output falls
Respiratory	↑ Inspiratory muscle pressure	Changes in thoracic cavity and elasticity of chest impair peak ventilation	Diaphragmatic weakening owing to intrinsic myocyte changes that further limit peak ventilation and increase energy needed to supply oxygen, and ↑ ergoreflex signalling with induced breathlessness
Pulmonary	Alveoli–pulmonary air gas exchange	↓ Alveoli, especially in context of lifelong tobacco exposure and/or air pollution	↑ Interstitial oedema, and impaired alveolar gas diffusion
		↑ Pulmonary pressures owing to typical left heart stiffening	↑↑ Pulmonary pressures continue owing to left heart failure, and often exacerbated by mitral regurgitation, atrial fibrillation, and/or aortic stenosis
Peripheral
Skeletal muscle	↑ Aerobic type I fibres to achieve muscle endurance	Atrophy of type II glycolytic fibres	↓ Percent and ↑ atrophy of type I oxidative fibres
	↑ Mitochondrial energetics, cellular metabolism, and gene expression to support physical capacity	↓ Mitochondrial function	↓↓ Mitochondrial volume density and oxidative enzyme activity owing to both deconditioning and direct effects of disease
	↑ Local redirection to augment microvascular perfusion	↓ Local perfusion (deconditioning often determinant)	• ↓↓ Local perfusion • ↓ Capillary density • ↓ Muscle oxygen diffusive conductance • Abnormal metaboreflex: ↑ muscle sympathetic nerve activity and ↓ muscle blood flow leading to ↑ substrate level phosphorylation and ↑ anaerobic glycolysis, such that fatigue occurs earlier and oxygen-uptake kinetics are slowed
	Endothelial responses	↓ Endothelial responses (owing to deconditioning)	↓↓ Endothelial-dependent vasodilatation
	Force generation	↓ Force generation (owing to deconditioning)	↓ Force generation

^*Variable, depending on habitual exercise, genetic constitution, and/or other idiosyncratic factors.