“Physiologic” murmurs occur when there is increased ejection velocity across a normal valve creating turbulence. Causes of increased velocity include fever, anemia, pregnancy, hyperthyroidism, exercise, and conditions associated with a large stroke volume (e.g., aortic regurgitation, bradycardia, atrial septal defect [ASD]). Dilation of the aorta, as in hypertension or aging, may also produce a flow murmur by causing turbulent flow in the dilated segment.

“Innocent” murmurs occur in normal hearts under resting conditions. The origin of such murmurs is a subject of debate, with recent evidence pointing to the aortic root. Because there is no obstruction in the outflow tract, the murmur reflects the normal ejection pattern of blood from the ventricles and is early systolic and crescendo-decrescendo. Because chamber pressures are normal, there is normal splitting of heart sounds. Valves are normal; there are no adventitious sounds or other murmurs.

Early aortic and pulmonic valve disease may produce murmurs identical to physiologic ones, except that the former are often accompanied by an early systolic ejection click. In pulmonic stenosis, the murmur increases with inspiration, and the pulmonic component of the second sound is delayed as the disease progresses, widening the splitting of the second heart sound. With increasing stenosis, ejection murmurs usually become louder and more prolonged, with peak intensity occurring later in systole. In hemodynamically significant aortic stenosis, a sustained left ventricular heave develops, the carotid upstroke becomes delayed and lower in amplitude (the parvus et tardus pattern), and the second heart sound becomes softer and single as the aortic closing sound decreases.

Calcific aortic stenosis is the most common cause of aortic stenosis in the elderly. Onset is in the fourth decade if the underlying valve is bicuspid and in the sixth to eighth decades if the valve is an otherwise normal tricuspid one. Most patients present with symptoms of advanced disease (angina, heart failure, syncope) because the condition often goes unrecognized in the asymptomatic phase. Early diagnosis is often made difficult by the speed of disease progression and the deceptively subtle and atypical physical findings in elderly persons with hemodynamically significant disease. Valve calcification can progress rapidly, leading to hemodynamically significant outflow tract obstruction in as little as 1 to 2 years. Unlike other forms of aortic stenosis, the murmur at the base may reappear at the apex as a higher-pitched sound and simulate mitral regurgitation (Gallavardin’s phenomenon). In addition, the left ventricular lift associated with hemodynamically significant disease may be less prominent due to myocardial decompensation, and the carotid upstroke may be normal if the carotid artery is stiff due to age.

Aortic sclerosis, also referred to as aortic valve thickening, is a precursor of calcific aortic stenosis, with 1-year risk of progression reported to be in excess of 15%. It is prevalent in the elderly (found in 40% of persons >75 years of age) and characterized by thickening of the aortic valve leaflets without causing outflow obstruction. Nonetheless, the condition is associated with an increased risk of cardiovascular morbidity and mortality, believed related to its association with atherosclerotic risk factors; however, only concurrent calcification of the mitral valve annulus has proven to be predictive of progression to hemodynamically significant aortic stenosis (perhaps reflective of a generalized process).

Hypertrophic cardiomyopathy produces an ejection quality murmur by dynamically obstructing the left ventricular outflow tract. Myocardial fibrosis is a hallmark of the condition and an early manifestation. Displacement of the mitral valve may also occur dynamically and cause regurgitation. The ejection murmur is affected by the size of the left ventricular cavity and contractility. Maneuvers that decrease cavity size (e.g., Valsalva) increase obstruction and intensify the murmur. When there is marked obstruction, the murmur lasts through most of systole, and its peak is delayed beyond midsystole. Some patients are prone to tachyarrhythmias. The electrocardiogram (ECG) shows high voltage.

ASDs produce physiologic murmurs due to increased right ventricular stroke volume. However, unlike other physiologic murmurs, there is often wide and fixed splitting of the second sound due to left-to-right shunting of blood and a delay in right ventricular ejection.

Patients with physiologic or innocent murmurs are generally asymptomatic from a cardiac standpoint and usually have no previous history of heart disease. Patients with mild varieties of aortic or pulmonic stenosis hypertrophic cardiomyopathy or a small ASD may be asymptomatic as well. In patients with aortic stenosis, onset of symptoms (e.g., angina, dyspnea, postural light-headedness) is usually a late development indicating advanced disease (see Chapter 33).

Holosystolic regurgitant mitral murmurs usually occur with conditions that render the mitral valve incompetent throughout systole and include rheumatic mitral valve disease, bacterial endocarditis, severe cases of dilated cardiomyopathy, papillary muscle rupture, and endocardial fibrosis of the valve surface. The latter has been associated with prolonged, high-dose use of the diet-pill combination phentermine/fenfluramine (see Chapter 234). The purported mechanism of valve fibrosis is excessive serotonergic effects on valve endocardial metabolism leading to clinically significant incompetence of mitral, tricuspid, and aortic valves.

Tricuspid regurgitation due to valve injury or right ventricular dilation produces a murmur similar in quality and timing to that of mitral regurgitation but is heard best along the left sternal border rather than the apex and characteristically increasing with inspiration.

Another mechanism of holosystolic murmur is left-to-right shunting, as occurs with ventricular septal defect (VSD). The holosystolic murmur of VSD is heard best at the left sternal border as a consequence of turbulence from the left-to-right shunting of blood. With prolonged shunting and resultant increase in right ventricular pressure, the pressure gradient and degree of shunting may decline and with it the intensity of the murmur. It is differentiated from tricuspid regurgitation by maneuvers that increase afterload (see later discussion).

Late-systolic regurgitant murmurs result from valve incompetence that develops as systole progresses. Mid- to late-systolic murmurs are characteristic of the mitral regurgitation due to mitral valve prolapse (MVP) and papillary muscle dysfunction associated with ischemic heart disease.

MVP is the most common cause of an asymptomatic mitral regurgitant murmur in the outpatient setting. The condition is characterized by myxomatous degeneration of the valve leaflets and chordae due to abnormal glucosaminoglycan composition, making them weaker and more likely to stretch and prolapse. In the Framingham study, the prevalence was initially reported to be as high as 17% among young women and 4% among young men. Use of more-stringent echocardiographic criteria and avoidance of selection bias has refined and reduced the estimated prevalence to 2.4%, with little difference between young men and young women. Women tend to have less severe disease than men, with less posterior prolapse, less leaflet flail, and less frequent severe regurgitation. MVP, with its late-systolic murmur, is often preceded by a click as the redundant mitral valve leaflets prolapse into the atrium during late systole. Most patients with MVP have no other signs or symptoms of heart disease, although an important minority experience atypical chest pain, dysrhythmias, or dyspnea. In a few instances, particularly in older men, hemodynamically significant mitral regurgitation occurs. Asthenic builds in both men and women have been associated with MVP, as has small breast size in women. Nonspecific T-wave changes, particularly inferior lead T-wave inversion, have been described. Diagnosis is confirmed by finding definite prolapse of mitral valve leaflets in the parasternal long-axis view on two-dimensional (B-mode) ultrasound study.