Myocardial relaxation and left ventricular diastolic function
Diastolic function is determined by the efficiency of myocardial relaxation. The degree and velocity of relaxation are the key parameters. Ideally, relaxation should proceed rapidly and the ventricle should expand substantially. This requires that the myocardium has high compliance, a term used to describe myocardial elasticity. The greater the compliance, the more rapid and pronounced the relaxation (i.e the stretching of myocardial fibers). The opposite is also true; the stiffer the myocardium, the slower and less pronounced the relaxation.
Left ventricular compliance
Multiple factors affect ventricular compliance. These factors include age, afterload, myocardial synchronization and intracellular processes (e.g intracellular calcium signaling, the sodium–potassium pump, mitochondrial function, actin-myosin interactions, etc.).
Afterload
Afterload is the resistance that the left ventricle must overcome to eject blood into the aorta. Afterload affects myocardial muscle fibers during systole and diastole. Afterload is a function of the following three variables:
- Aortic resistance (pressure).
- Left ventricular volume.
- Ventricular wall thickness (myocardial thickness).
The left ventricle must generate sufficient contractile force to overcome the pressure in the aorta. The greater the pressure in the aorta, the greater the load on individual muscle fibers. Also, the load on individual fibers is positively correlated with left ventricular volume, meaning that load on the muscle fibers increases as ventricular volume increases. However, there is an inverse relationship between wall thickness and load, such that greater wall thickness reduces the load on muscle fibers.
The exact mathematical relationship between aortic pressure, ventricular volume, and wall thickness is rather complicated and not within the scope of this discussion. The bottom line, however, is of direct clinical relevance and states that increased afterload results in a slower relaxation. Any condition leading to increased afterload will, therefore, lead to impaired diastolic function.
Increased afterload causes impaired diastolic function.
Myocardial synchronization
Myocardial synchronization refers to the sequence of activation of the ventricular myocardium. The ventricles should be depolarized (activated) by impulses spreading through the left and right bundle branch, which branches out into the Purkinje network (refer to Cardiac Electrophysiology: The Action Potential). Impulse conduction through the Purkinje network is rapid and coordinated, enabling synchronization of left and right ventricular contraction. Rapid impulse conduction is crucial; slow spread of the impulse results in temporal dissociation of cellular activation, and thus desynchronization of contraction. Importantly, the desynchronization of myocardial activation results in disturbed ventricular relaxation.
Desynchronization of myocardial activation causes impaired ventricular relaxation.
Impaired relaxation causes increased diastolic pressure in the left ventricle.
Disturbance in ventricular relaxation results in the disruption of pressure conditions in the left ventricle. Ventricular pressure should drop rapidly and substantially during diastole, but if relaxation is impaired, the drop in pressure will be slower and less pronounced. This ultimately leads to increased diastolic pressure in the left ventricle.
Impaired relaxation results in increased ventricular diastolic pressure.
Myocardial stiffness
Myocardial stiffness is inversely related to compliance; the stiffer the myocardium, the lower the compliance. Stiffness is determined by several factors, e.g ventricular geometry (a large ventricle yields greater afterload and consequently increasing diastolic pressure), sarcomere structure, the composition of extracellular matrix (extracellular fibrosis reduces compliance), pericardial status, etc.
Diastolic Dysfunction and Diastolic Heart Failure
Heart failure with preserved ejection fraction (HFPEF)
Diastolic heart failure accounts for approximately half of all cases of heart failure. The condition is characterized by diastolic dysfunction and normal systolic function. Ejection fraction–which is a measure of systolic function–should be 50% or higher. Diastolic heart failure is also referred to as heart failure with preserved ejection fraction (HFPEF). Echocardiography is the preferred modality for diagnosing diastolic dysfunction and heart failure.