Pathophysiology
In the young, the left ventricle becomes more compliant with age and the third heart sound will disappear during young adulthood.

In the middle aged and older age, it is usually a sign of increased thickness in the ventricular wall.  The growing ventricle looses its ability to relax during diastole and increases resistance to the ventricular filling. It is therefore considered an important clinical sign of early heart disease.

In mitral regurgitation, the subsequent increased flow into the ventricle will contribute to an audible S3.

In constrictive pericarditis, the S3 is called a pericardial knock, as it occurs slightly earlier and is of higher pitch.

The fourth heart sound is usually seen in context with significant aortic stenosis, Dialted and Hypertrophic Cardiomyophaty (HCM), systemic hypertension and in coronary artery diseases. The sound is generated by forceful atrial contraction and a stiffening of the ventricular wall.