Pathophysiology of Heart Murmurs
Fundamental Mechanism
Heart murmurs are generated by three primary mechanisms: high-velocity flow through normal or abnormal orifices, forward flow through a narrowed or irregular orifice into a dilated vessel or chamber, and backward or regurgitant flow through an incompetent valve. 1 The precise timing of onset and cessation depends on when a physiologically important pressure difference between two chambers occurs during the cardiac cycle. 1
Systolic Murmurs
Holosystolic (Pansystolic) Murmurs
These murmurs are generated when blood flows between chambers that maintain widely different pressures throughout the entire systolic period. 2 The pressure gradient and regurgitant jet begin early in contraction and persist until relaxation is nearly complete. 1
Specific pathophysiological mechanisms include:
Mitral regurgitation: Backward flow from left ventricle to left atrium caused by mitral valve prolapse with leaflet malcoaptation, rheumatic heart disease affecting valve leaflets, papillary muscle dysfunction or rupture, functional MR due to left ventricular dilation and annular enlargement, infective endocarditis with leaflet destruction, and congenital mitral valve abnormalities 3
Tricuspid regurgitation: Backward flow from right ventricle to right atrium caused by pulmonary hypertension causing right ventricular dilation, right ventricular failure with annular dilation, infective endocarditis, rheumatic heart disease, and carcinoid heart disease 3
Ventricular septal defects: Abnormal communications between left and right ventricles allowing left-to-right shunting due to the pressure difference, which can be congenital or acquired (including post-myocardial infarction) 3
Midsystolic (Systolic Ejection) Murmurs
These murmurs occur when blood is ejected across the aortic or pulmonic outflow tracts, typically with a crescendo-decrescendo configuration. 1 The murmurs start shortly after S1 when ventricular pressure rises sufficiently to open the semilunar valve, augment as ejection increases, and diminish as ejection declines. 1
Pathophysiological causes include:
Increased flow velocity through normal valves: Elevated cardiac output states such as pregnancy, thyrotoxicosis, anemia, and arteriovenous fistula 1
Valvular stenosis: Valvular, supravalvular, or subvalvular obstruction of either ventricle creates turbulent flow, with murmur intensity depending partly on blood flow velocity across the narrowed area 1
Ejection into dilated vessels: Flow into a dilated vessel beyond the valve or increased sound transmission through a thin chest wall 1
Functional regurgitation: Certain patients with functional mitral regurgitation or less frequently tricuspid regurgitation 1
Early Systolic Murmurs
These represent a subset of systolic murmurs with specific timing characteristics related to early pressure gradients. 1
Mid to Late Systolic Murmurs
These murmurs have delayed onset during systole, often associated with mitral valve prolapse where the pressure gradient develops later in systole. 1
Diastolic Murmurs
Diastolic murmurs virtually always represent pathological conditions and require further cardiac evaluation. 1
Early High-Pitched Diastolic Murmurs
These occur immediately after S2 and are caused by regurgitation through incompetent semilunar valves (aortic or pulmonic regurgitation) when diastolic pressure in the great vessel exceeds ventricular pressure. 1
Middiastolic Murmurs
These result from increased flow or obstruction across atrioventricular valves during the rapid filling phase of diastole, such as mitral stenosis or increased flow across a normal mitral valve. 1
Presystolic Murmurs
These occur during atrial contraction and represent accentuation of flow across stenotic atrioventricular valves during active atrial emptying. 1
Continuous Murmurs
Most continuous murmurs represent pathological conditions requiring further evaluation, with exceptions being venous hums and mammary souffles which are innocent. 1 These murmurs result from continuous pressure gradients throughout both systole and diastole, such as patent ductus arteriosus where aortic pressure exceeds pulmonary artery pressure throughout the cardiac cycle. 1
Clinical Significance and Pitfalls
Most systolic heart murmurs do not signify cardiac disease and many are related to physiological increases in blood flow velocity, whereas diastolic murmurs almost always indicate pathology. 1 A common pitfall is that innocent murmurs in children and young adults are typically midsystolic and originate from aortic or pulmonic outflow tracts, but echocardiography is often necessary to separate a prominent benign midsystolic murmur (grade 3) from one due to valvular stenosis. 1
Red flags indicating pathologic murmurs include holosystolic or diastolic timing, grade 3 or higher intensity, harsh quality, abnormal S2, maximal intensity at upper left sternal border, systolic click, or increased intensity when standing. 4