What are the four standard auscultatory areas for cardiac murmurs, how are murmurs classified by timing, quality, pitch, and location, and which murmur is most commonly heard in patients with Down syndrome?

Cardiac Murmur Locations, Classification, and Down Syndrome Association

Standard Auscultatory Areas

The four standard cardiac auscultation sites are the aortic area (right upper sternal border), pulmonic area (left upper sternal border), tricuspid area (left lower sternal border), and mitral area (apex). 1

Murmur Classification Framework

Timing Classification

• Systolic murmurs occur between S1 and S2 and are subdivided into holosystolic (pansystolic), midsystolic (ejection), early systolic, and late systolic types 1
• Holosystolic murmurs begin with S1 and continue throughout systole until S2, maintaining a plateau configuration, and are generated when blood flows between chambers with significant pressure differences throughout the entire systolic period 2, 3
• Midsystolic murmurs occur when blood is ejected across the aortic or pulmonic outflow tracts, typically with a crescendo-decrescendo configuration 2
• Diastolic murmurs occur between S2 and the next S1 and include early high-pitched, middiastolic, and presystolic types 1
• Continuous murmurs span both systole and diastole, resulting from continuous pressure gradients throughout both phases of the cardiac cycle 2

Intensity Grading

• Systolic murmurs are graded on a 1-to-6 scale based on intensity, with Grade 1 being very faint and Grade 6 being extremely loud 1
• Diastolic murmurs are typically graded on a 4-point scale, with Grade 1 being very faint and Grade 4 being very loud 1

Quality and Pitch

• Murmurs are classified by pitch as high-pitched, medium-pitched, or low-pitched 1
• Configuration describes the intensity pattern: crescendo (increasing), decrescendo (decreasing), crescendo-decrescendo (diamond-shaped, typical of ejection murmurs), or plateau (constant intensity, typical of holosystolic murmurs) 1

Location and Radiation

• The primary auscultation site should be documented (apex, left lower sternal border, left upper sternal border, or right upper sternal border) 1
• Radiation patterns are critical: mitral regurgitation murmurs typically radiate to the axilla, while aortic stenosis murmurs radiate to the carotids 3, 1

Specific Murmur Causes by Timing

Holosystolic (Pansystolic) Murmurs

• Mitral regurgitation produces a holosystolic murmur best heard at the apex radiating to the axilla, caused by backward flow from left ventricle to left atrium 2, 3
• Tricuspid regurgitation produces a holosystolic murmur loudest at the lower left sternal border that increases with inspiration, caused by backward flow from right ventricle to right atrium 2, 3
• Ventricular septal defects cause holosystolic murmurs due to abnormal communications between the left and right ventricles 2, 3

Midsystolic Murmurs

• Midsystolic murmurs are caused by increased flow velocity through normal valves, valvular stenosis, ejection into dilated vessels, or functional regurgitation 2
• These murmurs typically have a crescendo-decrescendo configuration and occur during ventricular ejection 2

Diastolic Murmurs

• Early high-pitched diastolic murmurs occur immediately after S2 and are caused by regurgitation through incompetent semilunar valves (aortic or pulmonic regurgitation) 2
• Middiastolic murmurs result from increased flow or obstruction across atrioventricular valves during the rapid filling phase of diastole 2

Clinical Significance and Red Flags

Diastolic murmurs virtually always represent pathological conditions and require further cardiac evaluation, regardless of intensity. 2, 1

• Most systolic heart murmurs do not signify cardiac disease, whereas diastolic murmurs almost always indicate pathology 2
• Holosystolic or late systolic murmurs at the apex or left sternal edge require echocardiography 1
• Midsystolic murmurs of grade 3 or greater intensity require echocardiography 1
• Pathologic murmurs include those with holosystolic or diastolic timing, grade 3 or higher intensity, harsh quality, maximal intensity at upper left sternal border, or increased intensity when standing 4

Down Syndrome and Associated Murmurs

Patients with Down syndrome most commonly have atrioventricular septal defects (endocardial cushion defects), which produce holosystolic murmurs best heard at the left lower sternal border. This is the most frequent congenital heart defect in Down syndrome, occurring in approximately 40-45% of affected individuals. The murmur results from the ventricular septal component of the defect, creating a holosystolic murmur due to left-to-right shunting between ventricles 2, 3.

Common Pitfalls

• Ventricular septal defects can present with varying murmur intensity depending on defect size—smaller defects often produce louder murmurs due to higher velocity flow through a restrictive orifice 2
• Right-sided murmurs (tricuspid regurgitation) increase with inspiration, while left-sided murmurs typically do not—this dynamic maneuver helps differentiate the source 3, 1
• In asymptomatic adults, grade 1-2 midsystolic murmurs at the left sternal border with normal S2 splitting and no other abnormalities are typically innocent and do not require workup 1