What are the common causes of a holosystolic murmur in a patient?

Holosystolic Murmur Causes

The three primary causes of holosystolic (pansystolic) murmurs are mitral regurgitation, tricuspid regurgitation, and ventricular septal defect—all representing pathological conditions that require echocardiographic evaluation. 1

Pathophysiological Mechanism

Holosystolic murmurs are generated when blood flows between two cardiac chambers that maintain widely different pressures throughout the entire systolic period, creating a characteristic plateau-shaped murmur that begins with S1 and extends through to S2. 2, 1 This distinguishes them from midsystolic ejection murmurs, which have a crescendo-decrescendo pattern. 2

Specific Causes and Clinical Features

Mitral Regurgitation

Mitral regurgitation is the most common cause of holosystolic murmurs in adults. 3 The murmur results from backward flow from the left ventricle to the left atrium throughout systole. 1

Key characteristics:

• Best heard at the cardiac apex with radiation to the axilla and left infrascapular area 1, 4
• Does not change intensity after ventricular premature beats (unlike stenotic valve murmurs) 2
• Increases with handgrip exercise and transient arterial occlusion 2
• Decreases with amyl nitrite inhalation 2

Common etiologies include:

• Mitral valve prolapse with leaflet malcoaptation 1
• Rheumatic heart disease affecting valve leaflets 1, 5
• Papillary muscle dysfunction or rupture 1
• Functional MR from left ventricular dilation and annular enlargement 1
• Infective endocarditis with leaflet destruction 1, 5
• Congenital mitral valve abnormalities 1

Tricuspid Regurgitation

Tricuspid regurgitation produces backward flow from the right ventricle to the right atrium. 1

Key characteristics:

• Best heard at the lower left sternal border (4th left parasternal border) 4, 6
• Increases with inspiration (Carvallo's sign)—the most reliable distinguishing feature from left-sided murmurs 4
• Does not change or diminishes after ventricular premature beats 2

Common etiologies include:

• Pulmonary hypertension causing right ventricular dilation 1
• Right ventricular failure with annular dilation 1
• Infective endocarditis (especially in injection drug users) 2, 1
• Rheumatic heart disease 1
• Carcinoid heart disease 1
• Traumatic papillary muscle rupture from blunt chest trauma 6

Ventricular Septal Defect

VSD creates a left-to-right shunt through an abnormal communication between ventricles. 1

Key characteristics:

• Best heard at the lower left sternal border 4
• Physical examination has 100% sensitivity for detecting VSD among organic causes of systolic murmurs 3
• Can be congenital or acquired (post-myocardial infarction, post-surgical) 1

Important caveat: In large VSDs with pulmonary hypertension, pressure equalization occurs at end-systole, eliminating the late systolic shunt and limiting the murmur to early-to-midsystole only. 2, 4 This represents an exception where VSD does not produce a true holosystolic murmur.

Diagnostic Approach

Echocardiography is the gold standard and should be performed in all patients with holosystolic murmurs, as these almost always indicate pathological conditions. 1, 4 Physical examination alone has significant limitations, particularly when multiple lesions coexist (present in 35% of patients with organic heart disease). 3

Dynamic Auscultation Maneuvers

Use these bedside maneuvers to differentiate causes before echocardiography:

• Respiration: Right-sided murmurs (tricuspid regurgitation) increase with inspiration; left-sided murmurs (mitral regurgitation) are louder during expiration 2, 4
• Handgrip exercise: Increases murmurs of MR and VSD by increasing afterload 2
• Standing: Most murmurs diminish, but MVP may lengthen and intensify 2
• Squatting: Most murmurs increase, but MVP murmurs soften 2
• Post-ventricular premature beat: Regurgitant murmurs (MR, TR, VSD) do not change or diminish, unlike stenotic valve murmurs which increase 2

Clinical Pitfalls

Avoid these common diagnostic errors:

• Missing combined valvular disease: In 35% of patients with organic murmurs, multiple abnormalities coexist, most commonly combined aortic and mitral valve disease. 3 Physical examination sensitivity drops to 55% for combined lesions. 3

• Misjudging severity in low ejection fraction: Aortic stenosis severity is frequently underestimated when left ventricular ejection fraction is severely diminished, as reduced stroke volume decreases murmur intensity. 3

• Confusing early systolic with holosystolic murmurs: Acute severe MR and TR without pulmonary hypertension may produce early systolic murmurs that end in midsystole rather than true holosystolic murmurs. 2, 4

• Overlooking MVP progression: MVP can present with either late systolic or pansystolic murmurs depending on severity; the presence of a holosystolic murmur indicates more severe regurgitation. 1

Red Flags Requiring Urgent Evaluation

Any holosystolic murmur accompanied by these findings mandates immediate echocardiography and cardiology consultation:

• Symptoms of heart failure, syncope, or angina 2
• Signs of endocarditis (fever, petechiae, Osler's nodes, Janeway lesions) 2, 5
• New murmur in the setting of chest trauma 6
• Grade 3 or higher intensity 7
• Abnormal S2 (fixed splitting suggests ASD; soft/absent A2 suggests severe AS) 2, 7