What is the differential diagnosis of a systolic heart murmur? What is the most likely diagnosis in your patient?

Systolic heart murmurs are common in practice and often benign (unlike diastolic murmurs, which are usually associated with some form of pathology). In young adults, although systolic murmurs are heard in 5 to 52% of patients, the echocardiogram is normal in 86 to 100% (this number is even higher in pregnant women referred for systolic murmurs), suggesting that echocardiograms are overutilized in this population. The subject of murmurs is further complicated by the fact that general internists are quite weak at identifying the cause of murmurs. In a 1997 JAMA study of 314 internal medicine and family practice residents, only 20% were able to correctly identify abnormal heart sounds from recordings. In another paper in JAMA (from the Rational Clinical Exam series) the precision of examining a grade 2 or louder murmur in the clinical setting is poor, with a kappa statistic of only 0.30 (this includes cardiologists).

Before discussing the heart murmurs that are caused by valvular and structural heart disease, it is worth noting that blood viscosity and velocity are also factors in producing a murmur. Don’t forget to think about noncardiac causes (such as anemia and thyrotoxicosis) when you hear abnormal systolic heart sounds. It’s also worth noting that a thorough history is the first and most important step in assessing a murmur. A systolic murmur in a 26-year-old female with anemia and heavy menstrual periods has different implications than one in a 46-year-old male with active intravenous (IV) drug use, fevers, and weight loss.

In general, pathologic murmurs are produced from the following valvular and structural abnormalities: aortic stenosis, mitral regurgitation (including due to mitral valve prolapse [MVP]), and tricuspid regurgitation and hypertrophic cardiomyopathy (HCM). Aortic stenosis (AS) is most likely to occur in older patients with calcification of the aortic valve but can also occur in younger patients with bicuspid aortic valves. It is loudest over the aortic valve area, located over the second intercostal space just to the right of the sternum. It can radiate to the right carotid artery and is not associated with a click. Your patient’s clinical history and murmur do not fit with AS. Tricuspid regurgitation (TR) occurs most often as a result of pulmonary pathology; however, it can rarely occur as a primary valvular problem (as when it occurs in Ebstein’s anomaly). TR is loudest over the tricuspid valve area, located over the left lower sternal border and is not associated with a click. Again, your patient’s clinical history and murmur do not fit. HCM is a heterogeneous condition of concern in a young patient as it can potentially be fatal. The vast majority of patients, though, are either asymptomatic or have nonspecific symptoms like your patient. The condition is caused most commonly by an inherited mutation in the heart muscle. The systolic murmur of HCM, especially when there is subaortic hypertrophy, is a harsh crescendo-decrescendo murmur that is best heard over the apex, located at the 5th or 6th intercostal space in the midclavicular line. It radiates to the left lower sternal border and is not associated with a click. Often a strong apical impulse can be palpated as well, signifying a hypertrophied left ventricle. Mitral regurgitation (MR), when it occurs as a result of MVP, is also a late systolic murmur heard loudest over the apex, occurring after a midsystolic click. The click is a distinct sound that happens as a result of the chordae tendinae suddenly tensing after the mitral valve prolapses into the left atrium.

Your patient has a distinct midsystolic click that none of the other valvular conditions have. In that same Rational Clinical Exam series article from JAMA, this systolic click with or without a murmur is sufficient to make a diagnosis of MVP. As we shall see soon, the rest of your patient’s clinical picture is consistent with MVP as well.