What is the differential diagnosis for a systolic murmur in a patient?

Differential Diagnosis for Systolic Murmurs

Systolic murmurs are classified by timing into holosystolic, midsystolic (ejection), early systolic, and late systolic types, with each pattern pointing to specific valvular or structural cardiac pathology that requires systematic evaluation. 1

Holosystolic (Pansystolic) Murmurs

These murmurs persist throughout systole from S1 to S2, indicating flow between chambers with widely different pressures: 1, 2

• Mitral regurgitation: High-pitched, blowing murmur best heard at the apex, radiating to the axilla 1, 2
• Tricuspid regurgitation: Best heard at the left lower sternal border, increases with inspiration (Carvallo's sign) 1, 2, 3
• Ventricular septal defect: Harsh murmur at the left lower sternal border, though large VSDs with pulmonary hypertension may produce only early systolic murmurs due to pressure equalization 1, 2

Midsystolic (Ejection) Murmurs

These crescendo-decrescendo murmurs begin after S1 and end before S2, originating from outflow tract obstruction or increased flow: 1

Pathologic Causes:

• Aortic stenosis: Most common pathologic cause, heard at the right upper sternal border (2nd right intercostal space) with radiation to carotids 4, 5. Look for soft/absent A2, reversed S2 splitting, delayed carotid upstroke (parvus et tardus), and S4 if severe 1, 5. Echocardiography is mandatory for any grade ≥3 midsystolic murmur, as physical examination cannot reliably distinguish benign from pathologic aortic stenosis 1, 4, 6

• Pulmonic stenosis: Similar murmur at left upper sternal border (2nd left intercostal space), with ejection sound heard only during expiration 1, 4

• Hypertrophic cardiomyopathy: Murmur at 4th left intercostal space that paradoxically increases with Valsalva (65% sensitivity, 96% specificity) and standing from squatting (95% sensitivity, 84% specificity) 1, 3

• Atrial septal defect: Grade 2/6 murmur at pulmonic area with fixed splitting of S2 during both inspiration and expiration 1, 4

• Bicuspid aortic valve: Ejection sound heard during both inspiration and expiration suggests this diagnosis 1, 4

Innocent (Functional) Murmurs:

These result from increased flow across normal valves in high-output states: 1, 4

• Pregnancy, thyrotoxicosis, anemia, arteriovenous fistula: All produce midsystolic murmurs from elevated cardiac output 1, 4
• Characteristics: Grade 1-2 intensity, left sternal border location, normal S2 with physiologic splitting, no other abnormal cardiac sounds 4
• No imaging required in asymptomatic patients with these characteristics 4

Early Systolic Murmurs

These begin with S1 and end in midsystole: 1, 2

• Tricuspid regurgitation without pulmonary hypertension: Most common cause 1, 2
• Acute mitral regurgitation: Can present as early systolic murmur 1
• Large VSD with pulmonary hypertension or small muscular VSD: Shunting becomes insignificant at end-systole 1

Late Systolic Murmurs

These start well after ejection begins and end before or at S2: 1

• Mitral valve prolapse: Soft to moderately loud, high-pitched at apex, often preceded by midsystolic click 1, 2. Murmur lengthens and intensifies with standing 1, 2
• Functional mitral regurgitation: Due to apical tethering and malcoaptation from annular/ventricular changes 1

Critical Diagnostic Maneuvers

Use dynamic auscultation to differentiate causes: 1, 3

• Inspiration: Right-sided murmurs increase (100% sensitivity, 88% specificity for right-sided lesions) 1, 3
• Valsalva strain: Most murmurs decrease except HCM (increases) and MVP (lengthens) 1, 3
• Standing: Most murmurs diminish except HCM and MVP (increase) 1, 2, 3
• Handgrip: Increases MR and VSD murmurs (68% sensitivity, 92% specificity), decreases AS 1, 3
• Post-PVC beat: Murmurs from stenotic valves increase; regurgitant murmurs unchanged or decrease 1, 2

Immediate Echocardiography Indications

Order echocardiography for: 4, 6, 7

• Any diastolic component (virtually always pathologic) 1, 4
• Grade ≥3 systolic murmur 1, 4, 6
• Any holosystolic or late systolic murmur 4
• Symptoms (syncope, angina, heart failure) 1
• Abnormal ECG or chest X-ray 1
• Clinical suspicion of endocarditis 1

Common Pitfalls

• Aortic regurgitation commonly presents with systolic murmur: 86% of moderate AR cases had systolic murmurs in screening, while diastolic murmurs were rare (14%) 8
• Physical examination misses combined lesions: Sensitivity only 55% for combined aortic and mitral disease 6
• Parvus et tardus may be absent in elderly with severe AS due to vascular stiffening 1
• Severely reduced ejection fraction can mask severity of AS on examination 6