If a systolic murmur intensifies on exhalation, what does this indicate and what is the appropriate next step in evaluation and management?

Systolic Murmur Intensifying on Exhalation

A systolic murmur that increases with exhalation indicates a left-sided cardiac lesion, most commonly mitral regurgitation, aortic stenosis, or ventricular septal defect. 1

Physiologic Basis

Left-sided murmurs become louder during expiration because expiration decreases venous return to the right heart, which increases relative left-sided blood flow and augments left-sided murmur intensity. 1 This is the fundamental principle distinguishing left-sided from right-sided cardiac pathology at the bedside.

• Right-sided murmurs (tricuspid regurgitation, pulmonic stenosis) increase with inspiration due to increased venous return 1
• The respiratory variation has 100% sensitivity and 88% specificity for identifying right-sided murmurs when they augment with inspiration 2

Differential Diagnosis Algorithm

Step 1: Determine Murmur Timing and Location

• Holosystolic murmur at apex: Suggests mitral regurgitation 1
• Midsystolic murmur at right upper sternal border: Suggests aortic stenosis 1
• Holosystolic murmur at left lower sternal border: Suggests ventricular septal defect 1

Step 2: Perform Dynamic Maneuvers

Handgrip exercise (increases afterload):

• Increases intensity of mitral regurgitation and ventricular septal defect murmurs (68% sensitivity, 92% specificity) 1, 2
• Does not significantly change aortic stenosis murmur 1, 2

Valsalva maneuver:

• Decreases most murmurs including mitral regurgitation, aortic stenosis, and ventricular septal defect 1
• Exception: Hypertrophic cardiomyopathy murmur becomes much louder (65% sensitivity, 96% specificity) 1, 3, 2

Standing from squatting:

• Decreases most murmurs 1
• Exception: Hypertrophic cardiomyopathy and mitral valve prolapse murmurs increase (95% sensitivity, 84% specificity for HCM) 1, 3, 2

Step 3: Assess Associated Physical Findings

For suspected aortic stenosis:

• Delayed, diminished carotid upstroke (parvus et tardus) suggests severe disease (likelihood ratio 6.8) 1, 4
• Soft or absent A2 component of S2 indicates severe stenosis (likelihood ratio 12.7) 1, 5, 4
• Critical pitfall: Parvus et tardus may be absent in elderly patients despite severe stenosis 1

For suspected mitral regurgitation:

• Left ventricular dilatation on precordial palpation with bibasilar rales suggests severe chronic disease 1
• Murmur augmentation with transient arterial occlusion (bilateral arm cuff inflation to 20 mmHg above systolic pressure) has 78% sensitivity and 100% specificity 1, 2

For suspected ventricular septal defect:

• Responds similarly to mitral regurgitation with handgrip and arterial occlusion 1, 2
• May be early systolic only if defect is small or pulmonary hypertension is present 1

Appropriate Next Steps

Immediate Evaluation

Obtain transthoracic echocardiography in all patients with systolic murmurs that increase with expiration, as physical examination alone has significant limitations:

• Cannot reliably distinguish severe from moderate aortic stenosis 4, 6
• Misses combined valvular lesions in 45% of cases 6
• Sensitivity for detecting aortic regurgitation is only 21% 6

Echocardiography Should Assess:

• Valve anatomy and function (area, gradients, regurgitation severity) 5
• Left ventricular size, wall thickness, and ejection fraction 5
• Peak aortic velocity and calculated valve area for stenosis quantification 5
• Mitral valve morphology for associated disease 5

Additional Testing Based on Findings

If severe aortic stenosis confirmed (peak velocity ≥4.0 m/s or valve area ≤1.0 cm²):

• Annual echocardiography and clinical review 5
• Valve replacement indicated if symptomatic (dyspnea, angina, syncope) or ejection fraction <50% 5

If discrepancy between clinical and echocardiographic findings:

• Consider cardiac catheterization for precise gradient measurement 5
• Perform coronary angiography if ischemic symptoms present 5

Common Pitfalls to Avoid

• Do not rely on murmur intensity alone: Loudness correlates poorly with severity, especially in larger patients 7
• Do not assume single pathology: 35% of patients with organic murmurs have multiple cardiac lesions 6
• Do not dismiss soft murmurs: Grade 2/6 murmurs can represent severe disease, particularly with reduced cardiac output 1
• Do not skip echocardiography based on "benign" examination: Physical examination completely misses significant disease in some patients and has limited accuracy for combined lesions 4, 6