Physiology, Cardiovascular Murmurs

Development

Murmurs of the cardiac system develop due to alterations in blood flow or mechanical operation. Depending on the cause, auscultation findings in pitch, volume, and rhythm may change. The development of murmurs is highly dependent on the etiology and is not always associated with a pathologic process[2][3]; benign murmurs are common in children and during pregnancy[4].

Murmurs develop from a multitude of mechanisms. Typical cases include low blood viscosity from anemia, septal defects, failure of the ductus arteriosus to close in newborns, excessive hydrostatic pressure on cardiac valves causing valve failure, hypertrophic obstructive cardiomyopathy, and valvular specific pathologies. Regardless of underlying etiology, all involve the creation of disturbed blood flow, which produces a murmur[5].

Related Testing

Auscultation

Murmurs are identifiable through auscultation using a manual or electronically enhanced stethoscope[6][7][8]. Description of murmurs is made using the following criteria, explained below: location, quality, and timing[9].

Location

• Aortic valve: second intercostal space at the right sternal border.
• Pulmonary valve: second intercostal space at the left sternal border.
• Tricuspid valve: fourth intercostal space at the left sternal border.
• Mitral valve: fifth intercostal space at the left midclavicular line.
• Radiation: Murmurs may radiate, allowing auscultation at remote locations

Quality: Intensity

• Grade I: faint murmur, barely audible
• Grade II: soft murmur
• Grade III: easily audible but without a palpable thrill
• Grade IV: easily audible murmur with a palpable thrill
• Grade V: loud murmur, audible with stethoscope lightly touching the chest
• Grade VI: loudest murmur, audible with stethoscope not touching the chest

Quality: Pitch

• High or low frequency
• Other descriptive terms: blowing, harsh, musical, rumbling, squeaky

Quality: Profile

• Crescendo: a murmur which increases in intensity
• Decrescendo: a murmur that decreases in intensity
• Crescendo-decrescendo: a murmur that initially increases in intensity, peaks, and then decreases in intensity
• Plateau: static intensity

Timing

• Systolic: occurs at or after S1, finishing before or at S2
• Diastolic: occurs at or after S2, finishing before or at S1
• Can be described as early, mid, late
• Other murmurs: systolic murmurs can be holosystolic, throughout systole; continuous murmurs begin in systole and terminate after S2

Maneuvers

Most murmurs will increase or decrease in volume when the patient performs certain maneuvers. This dynamic quality of murmurs is used as a clinical tool during the patient's physical exam to aid in diagnosing a specific murmur[10][11][12]. Some examples of how maneuvers change the intensity of particular murmurs include:

• Handgrip: Increases afterload. Hand gripping increases the strength of aortic regurgitation, mitral regurgitation, and ventricular septal defect murmurs. It decreases the intensity of murmurs due to hypertrophic obstructive cardiomyopathy and mitral valve prolapse.
• Squatting: Increases preload. Squatting increases the intensity of aortic stenosis, mitral stenosis, aortic regurgitation, and mitral regurgitation. It decreases the strength of murmurs due to hypertrophic obstructive cardiomyopathy and mitral valve prolapse.
• Valsalva: Decreases preload. Valsalva increases the strength of murmurs due to hypertrophic obstructive cardiomyopathy and mitral valve prolapse. It decreases the intensity of aortic stenosis, mitral stenosis, aortic regurgitation, mitral regurgitation, and ventricular septal defects.
• Standing abruptly: Decreases preload and has the same effects as Valsalva. Sudden standing increases the intensity of murmurs in hypertrophic obstructive cardiomyopathy and mitral valve prolapse. It decreases the strength of aortic stenosis, mitral stenosis, aortic regurgitation, mitral regurgitation, and ventricular septal defects.
• Amyl nitrate: Decreases afterload. Amyl nitrate increases the intensity of aortic stenosis, hypertrophic obstructive cardiomyopathy, and mitral valve prolapse. It decreases the severity of aortic regurgitation, mitral regurgitation, and ventricular septal defects.

Imaging

Symptomatic patients presenting with new murmurs are always investigated with imaging. An echocardiogram is preferred to evaluate cardiac structure and function because of its practicality, sensitivity, and specificity for detecting valvular diseases. It also dynamically evaluates the heart, allowing for the diagnosis of disease otherwise unseen on nondynamic imaging. Echocardiography and a chest X-ray are recommended by several major organizations such as the American College of Cardiology, the American Heart Association, and the European Society of Cardiology as the first imaging studies to perform to evaluate symptomatic murmurs.

Several types of echocardiography are available. The least invasive is trans-thoracic echocardiography. Trans-thoracic echocardiography allows for the accurate diagnosis of valvular diseases, embolism, endocarditis, and aortic dissection. It is the simplest echocardiographic method, but in some patients, images may be obstructed by the rib cage or excess tissue in obese patients. For these patients, another more invasive technique, trans-esophageal echocardiography, may be appropriate. Trans-esophageal echocardiography eliminates image obstruction by visualizing the heart via a transducer introduced into the esophagus.

Finally, cardiac catheterization can be utilized for identifying pathologies. The catheter is used to measure pressure and flow in the heart, providing valuable information to the provider. This is the most invasive form of identification and thus is typically reserved if other modalities fail. 

Pathophysiology

Common Murmurs and the Cardiac Disease States

Murmurs have been closely linked to a multitude of diseases throughout the centuries. There are several common murmurs and cardiac disease states from which each specific murmur develops.

Aortic stenosis

Aortic stenosis is caused by narrowing the aortic valve and is the most common valvular pathology in the developed world. Typically, the stenosis arises from senile calcification or a congenital anomaly, such as a bicuspid aortic valve. Less commonly, rheumatic heart disease can affect the aortic valve. The characteristic crescendo-decrescendo systolic murmur is auscultated at the right upper sternal border and may radiate to the carotid arteries.

Aortic Regurgitation

Aortic regurgitation, also known as aortic insufficiency, is a decrescendo blowing diastolic murmur heard best at the left lower sternal border, heard when blood flows retrograde into the left ventricle. This is most commonly seen in aortic root dilation and as sequelae of aortic stenosis.

Innocent or Flow Murmur

This type of murmur is usually mid-systolic, caused by increased cardiac output. It is associated with no symptoms, typically seen in childhood and pregnancy, and resolves spontaneously. 

Pulmonary stenosis

Pulmonary stenosis is a systolic murmur best heard at the upper left sternal border and commonly associated with tetralogy of Fallot, carcinoid syndrome, congenital rubella syndrome, and Noonan syndrome.

Tricuspid stenosis

This diastolic murmur best heard at the lower left sternal border. Typical causes include infective endocarditis, seen in intravenous drug users, and carcinoid syndrome. Prolonged tricuspid stenosis may lead to right atrial enlargement and arrhythmias.

Tricuspid regurgitation

This type of murmur is systolic, auscultated at the lower left sternal border. It is also associated with intravenous drug users and carcinoid syndrome.

Mitral stenosis

Mitral stenosis is a diastolic murmur, best heard at the left 5th midclavicular line. It is associated with infective endocarditis and chronic rheumatic heart disease

Mitral regurgitation

Mitral regurgitation is a systolic murmur, best heard at the left 5th midclavicular line with possible radiation to the left axilla. It is commonly associated with infective endocarditis, rheumatic heart disease, congenital anomalies, and inferior wall myocardial infarctions.

Mitral valve prolapse

This murmur is auscultated as an early systolic click, with a potential last systolic murmur. Prolapse is associated with chronic diseases of the valves and congenital anomalies.

Pulmonic stenosis

Pulmonic stenosis is the main murmur auscultated in infants with Tetralogy of Fallot. It is described as a crescendo-decrescendo systolic ejection murmur heard loudest at the upper left sternal border. Onset is typically from congenital causes but may be seen in chronic rheumatic heart disease.

Austin Flint murmur

This type of murmur is a mid-diastolic rumbling murmur heard best over the apex. It is speculated to occur due to an aortic regurgitant jet causing the anterior mitral valve leaflet to close prematurely. Austin Flint murmurs may be mistaken for mitral stenosis.

Atrial septal defect

This congenital defect is located between the left and right atria, which allows blood to flow freely. Typical auscultation reveals a loud and wide fixed split S2 at the upper left sternal border. More substantial atrial septal defects are quieter, while small ones are louder and have a harsh quality, due to less turbulence through a larger, unrestricted conduit.

Ventricular septal defect

This murmur is holosystolic, best heard at the apex. Like atrial septum defects, smaller holes typically present with louder and harder murmurs.

Hypertrophic obstructive cardiomyopathy

Hypertrophic obstructive cardiomyopathy is an inherited myocardial disease in which the myocardium undergoes hypertrophic changes. These changes cause a systolic ejection murmur due to the mitral valve hitting the thickened septal wall during systole. The murmur is heard best between the apex and the left sternal border. It becomes louder with any maneuver that decreases preload or afterload, such as Valsalva or abrupt standing. This effect occurs because the lower ventricular blood volume from reduced preload or afterload allows for a closer approximation of the mitral valve to the hypertrophied septal wall, causing more turbulent blood flow.

Patent ductus arteriosus

This distinct machine-like murmur is heard continuously at the left upper sternal border. Avoidance of NSAIDs is standard, due to potentially closing the life-sustaining conduit until assurance of proper cardiac function is established.

Turners syndrome

This inherited disease often presents with a murmur in young women, most commonly due to the presence of a bicuspid aortic valve or coarctation of the aorta. A bicuspid aortic valve will present as a systolic murmur best heard at the right second intercostal space. Coarctation of the aorta will present in both systole and diastole and is heard over the thoracic spine. The continuous harsh systolic component of the aorta's coarctation is due to turbulent blood flowing through the aorta's small diameter section. Its diastolic component is due to aortic regurgitation. Other causes of murmurs in these patients include hypoplastic left heart or aortic dissection.

Tetralogy of Fallot

The murmur in Tetralogy of Fallot will present in an infant and is usually due to pulmonic valve stenosis. Another possible source of murmur in these patients is from the ventricular septal defect. However, this is less likely because the ventricular septal defect is often large in Tetralogy of Fallot patients. Pulmonic valve stenosis is characterized as an early systolic click with a harsh systolic crescendo-decrescendo ejection murmur, best heard at the left upper sternal border. Unlike aortic stenosis, this murmur will not radiate to the carotids.

Carcinoid syndrome

Carcinoid syndrome causes thickening of the tricuspid and pulmonary valves, which leads to either stenosis or regurgitation murmurs from the valves. This thickening arises from high amounts of serotonin released from the carcinoid tumor after the tumor has metastasized to the liver.

Chronic rheumatic heart disease

Chronic rheumatic heart disease is a sequela of untreated streptococcal pharyngitis and acute rheumatic fever. Autoimmune driven destruction occurs as a result of molecular mimicry between streptococcal M protein and the cardiac tissue.

Infective endocarditis

Infective endocarditis is associated with bacterial vegetative growths, most commonly seen on the tricuspid valve. This can lead to tricuspid stenosis and tricuspid regurgitation.

Prosthetic Valve Leaks

Murmurs may develop from a leak in any of the prostheses available for the four cardiac valves.

Clinical Significance

When combined with an accurately identified murmur, a patient history can provide critical details that lead to diagnosis[13]. Intravenous drug use, a history of untreated streptococcal pharyngitis or scarlet fever, valve replacement history, and a family history of cardiovascular disease or genetic disease are important historical items to be aware of in a patient with a murmur[14].

In addition to patient history, obtaining a detailed cardiovascular physical examination is paramount in identifying a murmur and its associated disease[15]. Begin by auscultating the four cardiac listening posts to determine the cardiac murmur's location and allow for its characterization[16]. Murmurs are described using the thoracic cage position where they are auscultated, pitch, volume, and in which phase of the cardiac cycle they occur. Auscultating other locations such as the axilla and carotid arteries also help accurately diagnose the murmur. It should be performed on any patient with a suspicion of a murmur. More severe murmurs are associated with thrills, which are palpable vibrations. Murmurs are graded in intensity from 1 to 6 using the Levine grading scale.

Murmurs are critical physical examination findings in many patients. Many diseases have associated murmurs[9]. Fortunately, each murmur often has enough distinguishing qualities that, when combined with patient history, allows the physician to create a concise list of possible diagnoses. Imaging such as an echocardiogram is essential for a definitive diagnosis of any underlying cardiac disease.

The skill of accurately describing a murmur is just as important as gathering a patient’s history. For example, the ability to accurately report whether a murmur is heard in systole or diastole in a healthy-appearing child is essential. The difference will determine whether or not to refer the patient to a pediatric cardiologist for further evaluation.