What are the potential causes and next steps in evaluating an ejection systolic murmur in a patient?

Differential Diagnosis of Ejection Systolic Murmurs

An ejection systolic murmur requires systematic evaluation based on its characteristics, associated findings, and grade, with echocardiography mandatory for any grade ≥3 murmur, any diastolic component, or concerning clinical features. 1

Pathologic Causes

Valvular Obstruction

• Aortic stenosis is the most common pathologic cause, producing a crescendo-decrescendo murmur best heard at the right upper sternal border (2nd right intercostal space) that radiates to the carotids 2, 3
• A soft or absent A2, reversed splitting of S2, delayed carotid upstroke, and humming quality to the murmur strongly suggest aortic stenosis 2
• Pulmonic stenosis produces a similar murmur at the left upper sternal border (2nd left intercostal space), with an ejection sound heard only during expiration 2, 3
• An early aortic systolic ejection sound heard during both inspiration and expiration suggests a bicuspid aortic valve 2

Subvalvular and Supravalvular Obstruction

• Hypertrophic cardiomyopathy causes dynamic left ventricular outflow tract obstruction, uniquely increasing with Valsalva maneuver (65% sensitivity, 96% specificity) and standing (95% sensitivity, 84% specificity) 1
• Subvalvular aortic stenosis and supravalvular aortic stenosis can produce similar murmurs, with intensity depending on blood flow velocity across the narrowed area 2

Structural Defects

• Atrial septal defect presents with a grade 2/6 midsystolic murmur at the pulmonic area and left sternal border, with fixed splitting of S2 during both inspiration and expiration 2
• Ventricular septal defects with pulmonary hypertension may produce an early-to-midsystolic murmur when end-systolic pressure equalization eliminates the shunt 2

Regurgitant Lesions

• Functional mitral regurgitation and less commonly tricuspid regurgitation can produce midsystolic murmurs 2

Innocent (Functional) Murmurs

Benign flow murmurs are characterized by grade 1-2 intensity at the left sternal border, normal S2 with physiologic splitting, and absence of other abnormal cardiac sounds. 1

High-Output States

• Pregnancy, thyrotoxicosis, anemia, and arteriovenous fistula all increase cardiac output, producing innocent midsystolic murmurs across normal semilunar valves 2, 1
• These murmurs result from increased flow rate rather than structural abnormality 2

Anatomic Variants

• Ejection into a dilated vessel beyond the valve or increased sound transmission through a thin chest wall can produce innocent murmurs 2
• Most innocent murmurs in children and young adults originate from aortic or pulmonic outflow tracts 2

Diagnostic Approach

Physical Examination Maneuvers

• Valsalva maneuver: Most murmurs decrease except hypertrophic cardiomyopathy, which increases 1, 3
• Standing from squatting: Hypertrophic cardiomyopathy and mitral valve prolapse increase 1, 3
• Handgrip exercise: Increases mitral regurgitation and ventricular septal defect (68% sensitivity, 92% specificity) while decreasing aortic stenosis 1
• Respiration: Right-sided murmurs increase with inspiration; left-sided murmurs increase with expiration 3

Indications for Echocardiography

Echocardiography is mandatory for: 1

• Any grade ≥3 midsystolic murmur (physical examination cannot reliably distinguish benign from pathologic aortic stenosis) 2, 1
• Any diastolic component (virtually always represents pathology) 1
• All holosystolic or late systolic murmurs 1
• Any systolic murmur with symptoms (heart failure, syncope, myocardial ischemia) or signs of endocarditis 1

When Echocardiography May Be Deferred

• Asymptomatic patients with grade 1-2 ejection systolic murmur, otherwise normal cardiac examination, and characteristics consistent with innocent murmur do not require extensive workup 1

Clinical Pitfalls

Physical examination has significant limitations: 4, 5

• Sensitivity for detecting intraventricular pressure gradients is only 18%, aortic regurgitation 21%, and combined aortic-mitral valve disease 55% 4
• Physical examination cannot reliably distinguish severe aortic stenosis from less severe stenosis, particularly with severely diminished left ventricular ejection fraction 4, 5
• In 35% of patients with organic heart disease, more than one abnormality is present, complicating clinical diagnosis 4
• Classic physical findings, despite proven value, are absent in many patients with significant cardiac lesions 5