Why is the diastolic phase of the cardiac cycle more energy-dependent?

Why Diastole is More Energy-Dependent Than Systole

Diastole is more energy-dependent than commonly appreciated because myocardial relaxation is an active, ATP-consuming process that requires energy to pump calcium back into the sarcoplasmic reticulum and extrude calcium from the cell, making it particularly vulnerable to conditions that impair energy production. 1

The Active Nature of Diastolic Relaxation

Contrary to the misconception that diastole is a passive phase, diastolic relaxation is fundamentally an energy-consuming process that involves several ATP-dependent mechanisms 1, 2:

• Calcium reuptake requires ATP to pump free myoplasmic calcium back into the sarcoplasmic reticulum, which is the primary mechanism controlling myocardial relaxation in mammals 1, 3
• Calcium extrusion from the cell involves the calcium-sodium exchange mechanism, which while not directly requiring ATP, necessitates subsequent sodium extrusion via sodium/potassium ATPase 1
• ATP-dependent calcium pumps also contribute to removing calcium that enters during the action potential plateau phase 1

Why Diastole is Particularly Vulnerable to Energy Depletion

Relaxation is intrinsically a much slower process than activation, making it more susceptible to energy deficits 1:

• When ATP production is limited, calcium remains bound to troponin during part or all of diastole, resulting in slower isovolumic relaxation and reduced myocardial distensibility 1, 4
• Changes in ATP concentration affect calcium efflux through allosteric effects, further impairing relaxation 1
• Impaired relaxation and reduced diastolic distensibility are almost universal in chronic congestive heart failure, where energy depletion is common 1

Clinical Manifestations of Energy-Dependent Diastolic Dysfunction

The energy dependence of diastole becomes clinically apparent in several conditions 1, 4:

• High-demand myocardial ischemia causes alterations in diastolic function due to inadequate energy production 1
• Acute ischemia specifically impairs diastolic function by slowing isovolumic relaxation (reduced peak negative dP/dt, increased time constant T), delaying left ventricular filling, and altering passive elastic properties 4
• Heart failure states are accompanied by energy depletion with alterations in mitochondrial density and enzymatic activity, reducing ATP production 1

Structural Factors Contributing to Energy Imbalance

Several anatomic and pathologic factors exacerbate the energy demands of diastole 1:

• Inadequate capillary network growth in hypertrophied myocardium limits oxygen and substrate delivery 1
• Impaired subendocardial perfusion due to increased diastolic wall stress and/or coronary artery disease creates an imbalance between energy production and utilization 1
• Myocardial fibrosis in conditions like aortic stenosis increases passive stiffness, requiring more energy for adequate relaxation 5

Important Clinical Caveats

Reduced myocardial relaxation is one of the earliest manifestations of myocardial dysfunction and occurs consistently in all forms of myocardial disease including hypertensive heart disease, myocardial ischemia, and hypertrophic cardiomyopathy 5:

• Patients with diastolic dysfunction cannot augment myocardial relaxation with exercise compared to normal subjects, achieving required cardiac output only at the expense of increased filling pressures 5
• Optimal therapy for heart failure should aim at improving diastolic function, not just systolic performance 1
• The energy dependence of diastole explains why diastolic dysfunction often precedes systolic dysfunction in many cardiac diseases 2