Ejection Systolic Murmur Diagnosis

Pathologic Causes

• Aortic stenosis is the most common pathologic cause, producing a crescendo-decrescendo murmur best heard at the right upper sternal border that radiates to the carotids, as suggested by the American College of Cardiology 1
• The American College of Cardiology recommends that a soft or absent A2, reversed splitting of S2, delayed carotid upstroke, and humming quality to the murmur strongly suggest aortic stenosis 1, 2
• Pulmonic stenosis produces a similar murmur at the left upper sternal border, with an ejection sound heard only during expiration, according to the American College of Cardiology 1
• An early aortic systolic ejection sound heard during both inspiration and expiration suggests a bicuspid aortic valve, as noted by the American College of Cardiology 1, 2
• Subvalvular aortic stenosis and supravalvular aortic stenosis can produce similar murmurs, with intensity depending on blood flow velocity across the narrowed area, as reported by the American College of Cardiology 1, 3
• 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, according to the American College of Cardiology 1, 2
• Ventricular septal defects with pulmonary hypertension may produce an early-to-midsystolic murmur when end-systolic pressure equalization eliminates the shunt, as suggested by the American College of Cardiology 1, 3
• Functional mitral regurgitation and less commonly tricuspid regurgitation can produce midsystolic murmurs, as noted by the American College of Cardiology 1, 3

Innocent (Functional) Murmurs

• Pregnancy, thyrotoxicosis, anemia, and arteriovenous fistula all increase cardiac output, producing innocent midsystolic murmurs across normal semilunar valves, according to the American College of Cardiology 1, 3
• These murmurs result from increased flow rate rather than structural abnormality, as reported by the American College of Cardiology 1
• Ejection into a dilated vessel beyond the valve or increased sound transmission through a thin chest wall can produce innocent murmurs, as suggested by the American College of Cardiology 1, 3
• Most innocent murmurs in children and young adults originate from aortic or pulmonic outflow tracts, according to the American College of Cardiology 1, 3

Diagnostic Approach

• The American College of Cardiology recommends that echocardiography is mandatory for any grade ≥3 midsystolic murmur, as it cannot reliably distinguish benign from pathologic aortic stenosis 2

Evaluation of Ejection Systolic Murmurs

Initial Clinical Assessment

• The American College of Cardiology recommends that in asymptomatic patients with a grade 1-2 ejection systolic murmur and an otherwise normal cardiac examination, extensive workup is not necessary; however, echocardiography should be performed for any grade ≥3 murmur, any diastolic component, or when clinical features suggest pathology 4, 5
• Ejection systolic murmurs are characterized by a crescendo-decrescendo pattern, starting after S1 when ventricular pressure opens the semilunar valve, peaking mid-systole, and ending before S2, which distinguishes them from holosystolic murmurs 6, 7, 8
• The Valsalva maneuver can help differentiate causes of murmurs, with most murmurs decreasing, but hypertrophic cardiomyopathy increasing (65% sensitivity, 96% specificity) 4
• Standing from squatting can also help differentiate causes, with hypertrophic cardiomyopathy and mitral valve prolapse increasing (95% sensitivity, 84% specificity for HCM) 9
• Handgrip exercise can increase mitral regurgitation and ventricular septal defect (68% sensitivity, 92% specificity), while aortic stenosis decreases 5

Indications for Echocardiography

• Echocardiography is mandatory for all diastolic murmurs, as they virtually always represent pathology 6, 10
• The American College of Cardiology recommends echocardiography for grade ≥3 midsystolic murmurs, as they cannot reliably distinguish benign from pathologic aortic stenosis by examination alone 4, 8
• Echocardiography is also indicated for all holosystolic or late systolic murmurs, as they indicate regurgitant lesions requiring evaluation 4, 5
• Any systolic murmur with symptoms, including heart failure, syncope, myocardial ischemia, or signs of endocarditis, requires echocardiography 5, 9

Characteristics of Innocent Murmurs

• Innocent murmurs are characterized by a grade 1-2 intensity at the left sternal border, a systolic ejection pattern, normal S2 intensity and physiologic splitting, and no other abnormal cardiac sounds 5, 9
• These murmurs do not require imaging in asymptomatic patients and are especially common in high-output states, including pregnancy, thyrotoxicosis, anemia, and arteriovenous fistula 7, 10

Systolic Murmur Diagnosis

Holosystolic Murmurs

• The American College of Cardiology notes that holosystolic murmurs persist throughout systole from S1 to S2, indicating flow between chambers with widely different pressures 11, 12
• Mitral regurgitation is characterized by a high-pitched, blowing murmur best heard at the apex, radiating to the axilla, according to the American Heart Association 11
• Tricuspid regurgitation is best heard at the left lower sternal border, increases with inspiration, as noted by the American College of Cardiology 11
• Ventricular septal defect is associated with a harsh murmur at the left lower sternal border, though large VSDs with pulmonary hypertension may produce only early systolic murmurs, as reported by the American College of Cardiology 11, 12

Midsystolic Murmurs

• The American College of Cardiology recommends that echocardiography is mandatory for any grade ≥3 midsystolic murmur, as physical examination cannot reliably distinguish benign from pathologic aortic stenosis 13
• Aortic stenosis is the most common pathologic cause of midsystolic murmurs, heard at the right upper sternal border with radiation to carotids, according to the American College of Cardiology 12
• Pulmonic stenosis is similar to aortic stenosis, with a murmur at the left upper sternal border, and an ejection sound heard only during expiration, as noted by the American College of Cardiology 12
• Hypertrophic cardiomyopathy is associated with a murmur at the 4th left intercostal space that paradoxically increases with Valsalva and standing from squatting, as reported by the American College of Cardiology 14

Diagnostic Maneuvers

• The American College of Cardiology notes that inspiration increases right-sided murmurs, with 100% sensitivity and 88% specificity for right-sided lesions 14
• Valsalva strain decreases most murmurs, except for hypertrophic cardiomyopathy and mitral valve prolapse, which increase, as reported by the American College of Cardiology 14
• Standing diminishes most murmurs, except for hypertrophic cardiomyopathy and mitral valve prolapse, which increase, according to the American College of Cardiology 14

Echocardiography Indications

• The American College of Cardiology recommends immediate echocardiography for any diastolic component, grade ≥3 systolic murmur, or symptoms such as syncope, angina, or heart failure 11, 13, 14
• Echocardiography is also indicated for abnormal ECG or chest X-ray, or clinical suspicion of endocarditis, as noted by the American College of Cardiology 14