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The third heart sound, or S3, is indicative of volume overload and is often associated with heart failure. This sound occurs during the rapid filling phase of the ventricles, typically shortly after S2. It reflects the increased fluid volume and pressure within the heart and can suggest that the left ventricle is not effectively managing the volume, often seen in conditions such as congestive heart failure.

In contrast, S1 marks the closure of the atrioventricular valves at the beginning of systole and does not specifically relate to volume overload. S2 is connected to the closure of the semilunar valves and indicates the end of systole, while S4 is associated with atrial contraction and typically indicates reduced ventricular compliance, often seen in conditions such as hypertrophy rather than volume overload. Thus, the third heart sound provides the strongest indication of the heart's struggle to accommodate increased volume, making it a key finding in the assessment of heart failure.