The most common types of acquired adult valvular heart diseases and associated murmurs

Essentials

• Heart murmurs are usually generated by a turbulent and increased flow of blood.
• The majority of soft systolic murmurs are innocent (benign).
• The intensity (loudness) of a murmur does not always correlate with the severity of the valvular disease.
• The intensity of a murmur induced by significant valvular disease usually decreases in severe heart failure, or the murmur may even disappear altogether.
• A murmur suggestive of new valvular regurgitation in a febrile patient should always arouse the suspicion of endocarditis.
• If the condition of a patient with an artificial heart valve suddenly deteriorates, complications relating to the valve prosthesis should always be borne in mind.
• Endocarditis prophylaxis is no longer considered necessary in patients with acquired valvular disease.
• This article does not address causes of murmurs that are rare in adults, including pulmonary valve stenosis, mitral valve stenosis, congenital heart diseases, ventricular septal defect and pericardial rub.

The principal aims of clinical assessment

• Is the murmur caused by a valvular disease or is it innocent?
• Are the patient’s symptoms (dyspnoea, reduced exercise capacity, chest pain) and ECG changes (LVH) caused by valvular disease?
• When should a patient with a new murmur or valvular disease be referred to specialist care for echocardiography and cardiologist consultation?
• When is emergency care or urgent specialist consultation indicated?
• On what should the follow-up focus and at what point is surgical management indicated?

Systolic murmurs

Aortic stenosis (AS)

Incidence and pathogenesis

• The most frequent adult valvular disease in the West (accounts for about 40% of all cases of valvular disease).
• Increases in incidence with age: at the age of 80 years, mild valvular stiffening and calcification affects half of the individuals, and 4% are affected by critical stenosis. AS must therefore always be considered as a possible cause of heart failure in an elderly patient.
• In the majority of cases the condition is caused by the degeneration of a normal tricuspid valve, and 15–20% of cases are caused by the stiffening of a bicuspid valve. Rheumatic fever is a rare cause of AS in the West.
• 1–2% of the population have a bicuspid aortic valve, which is susceptible to degeneration and may cause valvular stenosis or regurgitation in middle age.
• Valvular stenosis is an active inflammatory process which shares many similarities with atherosclerosis, and the same risk factors (age, male gender, cholesterol, hypertension, smoking) contribute to the development of stenosis.

Signs and symptoms

• Symptoms are non-specific and develop late as the stenosis progresses.
• The most common symptom is dyspnoea or chest pain on exertion, whereas syncope associated with sudden strenuous exercise is rarer and is suggestive of severe stenosis.
• Some patients reduce (unconsciously) the amount of exercise they take, and symptom assessment alone may therefore be misleading.
• A critically narrowed valve orifice, ventricular pump failure or the onset of atrial fibrillation (AF) may precipitate overt heart failure and pulmonary oedema, and the murmur may no longer be audible.
• Sudden death is rare in asymptomatic patients, but its incidence increases rapidly with the appearance of exercise-induced symptoms.
• A bleeding tendency, particularly gastrointestinal bleeding (angiodysplasia), affects about one fifth of patients with significant valvular stenosis. It usually resolves after valve surgery.
• Murmur (picture /3)
  • Has a harsh quality, peaks in mid-to-late systole. An early systolic ejection murmur is associated with a less stenotic valve, while a more prolonged late systolic murmur suggests a more severe degree of stenosis.
  • The murmur is transmitted from the aortic region to the neck and, particularly in elderly persons, to the apex leading to its misinterpretation as a murmur of mitral regurgitation.
  • As the valve becomes more stenotic, the closure sound (S2) becomes less audible. If AS is accompanied with aortic insufficiency, diastolic regurgitant murmur will also be heard. Hypertrophy may lead to atrial gallop (S4).
  • Severe heart failure may render the murmur deceptively faint, or it may become totally inaudible, even in the presence of advanced stenosis.
• Other findings
  • Palpation of the heart will reveal a sustained and forceful apex beat. The carotid pulse is usually diminished and rises slowly (”parvus et tardus"), but in elderly and overweight patients this finding may be difficult to assess.
  • ECG findings often include signs of LVH (both QRS criteria and ST changes) as well as left atrial strain.
  • Chest x-ray is generally normal. The ascending aorta may be dilated and valve calcification may be visible on a lateral view.

Diagnosis

• In principle, it is possible to clinically diagnose and estimate the severity of AS, but in practice Doppler echocardiography is the key imaging study both for the diagnosis and the assessment of disease severity.
• Echocardiography confirms the presence of AS, and it can usually be used to reliably assess the structure of the valve and the outflow obstruction caused (valve gradient). The study also allows assessment of any changes, caused by the defective valve, in the structure and function of the left ventricle. Stenosis is considered to be severe if the mean systolic pressure gradient is greater than 40 mmHg or the valve area less than 1 cm². In the presence of depressed cardiac output, even relatively low pressure gradients may be indicative of severe stenosis.
• Invasive investigations (cardiac catheterisation) are usually not needed in the diagnostic workup. However, coronary angiography or CT scanning is indicated before valvular surgery if coexistent coronary heart disease is suspected.

Follow-up and management

• Patients with mild stenosis (mean pressure gradient under 25 mmHg) should be clinically monitored in primary care with occasional echocardiograms recorded in specialist care if indicated.
• Echocardiography should be repeated and the patient’s eligibility for surgery considered if symptoms emerge during the primary care follow-up, changes are noted in the murmur or the ECG worsens.
• Patients with moderate stenosis (peak gradient approximately 30–40 mmHg) are clinically monitored in specialist care with occasional echocardiography. The follow-up visits should be more frequent if the valve is much calcified as heavy valve calcification is predictive of fast disease progress.
• Medium to severe AS is generally monitored in specialist care, provided that the patient is eligible for surgery or other intervention. More frequent follow-up visits are warranted if the condition worsens or if there are signs of deteriorating left ventricular (LV) function.
• No pharmacological therapies are available at present to halt the progress of AS.
• However, hypertension and other risk factors in a patient with AS must be appropriately managed. Suitable antihypertensive drugs are beta-blockers, diuretics and ACE inhibitors. Vasodilators should be avoided if the stenosis is severe.
• Sudden physical exertion should be avoided in marked valvular stenosis.
• Severe symptomatic AS is treated with aortic valve replacement surgery.
• Surgery should always be considered in symptomatic AS; there is no upper age limit provided that the patient is physically active and no severe comorbidities exist. Without surgery the prognosis is poor, and surgery clearly improves the long-term outcome.
• Surgery is indicated for asymptomatic patients with severe AS if LV function is showing signs of deterioration (ejection fraction < 50%). Surgery may also be considered for asymptomatic patients with severe stenosis and severe left ventricular hypertrophy, clearly increased natriuretic peptide concentration, abnormal exercise test performance or an exercise-induced fall in blood pressure.
• Mechanical valves are usually used in young to middle-aged patients and bioprosthetic valves in elderly patients.
• If the operative risk is high, a percutaneous technique known as transcatheter aortic valve implantation (TAVI) is increasingly used as a treatment alternative .
• In association with coronary artery bypass operation, concomitant surgical treatment of even a milder aortic stenosis is considered.

Mitral regurgitation (MR)

• The second most frequent adult valvular disease
• MR may be caused by abnormalities in the structure of the cusps, valve annulus, chordae tendinae or papillary muscles (structural mitral regurgitation), or it may occur as a consequence of LV dilatation and dysfunction, in most cases caused by either a myocardial infarction damage or dilated cardiomyopathy (functional mitral regurgitation).
  • The most common structural defect causing significant chronic valvular regurgitation is mitral valve prolapse.
  • The most frequent cause of an acute or suddenly worsening insufficiency is chordal rupture.
  • Rarer causes include rupture of the papillary muscles, endocarditis and cardiac trauma.

Signs and symptoms

• Mild to moderate MR usually does not cause symptoms, and even severe chronic MR may remain asymptomatic for a long time.
• Pulmonary congestion may gradually lead to dyspnoea, which initially occurs on exertion and as the disease progresses also at rest.
• Poor exercise tolerance is mainly caused by reduced cardiac output.
• Mitral valve prolapse may cause palpitations and chest pain, and if AF develops the patient may be aware of the irregular heart beat.
• In right heart failure, the legs and liver will become oedematous and the patient’s weight will increase.
• Acute massive mitral regurgitation will quickly lead to pulmonary oedema and even to cardiogenic shock.
• Murmur (picture /6)
  • A high frequency, pansystolic blowing murmur heard in the area between the cardiac apex and midaxillary line.
  • The murmur of a prolapsed posterior cusp may radiate towards the upper sternum and be mistaken for the murmur of AS.
  • In mitral valve prolapse, the sudden protrusion of the valve back into the atrium causes a mid-systolic click followed by a late-systolic regurgitant murmur.
  • In severe insufficiency, the closure sound (S1) of the valve is often noticeably quieter and ventricular gallop (S3) may be audible.
  • The intensity of the murmur does not correlate with the magnitude of regurgitation. If the LV contractility is well preserved, the murmur will also be loud and vice versa: as the LV contractility decreases so will the intensity of the murmur. A regurgitant murmur caused by papillary muscle damage, resulting from an MI, is usually soft even when the regurgitant volume is large.
• Other findings
  • The apex beat of the enlarged LV is felt over a wider area and more laterally than normal.
  • In mild to moderate MR, the ECG is usually normal. In severe MR, signs of both left ventricular (LVH) and left atrial (PTF) strain will gradually become evident, and the risk of AF increases.
  • A chest x-ray will show an enlarged left atrium and ventricle, and pulmonary vascular congestion may be present in severe chronic MR.
  • In acute severe MR, the heart may be of normal size and the radiographic signs of pulmonary oedema may erroneously be interpreted as signifying chest infection.
• Echocardiography and Doppler study
  • The key imaging study used for the diagnosis of MR as well as for the assessment of disease severity and timing for surgery.
  • Slight backflow (Grade 1) from a valve with normal anatomy is a common and normal finding and does not warrant further measures or follow-up.

Follow-up and management

• Patients with mild MR but otherwise normal echocardiographic findings can be clinically followed every few years, unless signs of deterioration occur.
• Patients with moderate MR should be seen annually and echocardiography preformed every 1–2 years, provided that the LV function is preserved and there are no signs of ventricular enlargement.
• The management of severe asymptomatic MR requires specialist intervention. The patient is followed up every 6–12 months: careful assessment of the functional capacity, LV size, pumping capacity of the heart and pulmonary artery pressure in order to optimise the time of surgical intervention.
• Severe acute MR caused by chordal rupture or endocarditis will often quickly lead to pulmonary oedema; immediate surgery is indicated in this situation.
• No pharmacological therapies are available to halt the progress of MR, and pharmacological therapy is not indicated in chronic asymptomatic MR.
• The drugs of choice in acute heart failure are diuretics and vasodilators (an ACE inhibitor and nitrate). AF is managed in accordance with the usual principles (beta-blocker, digoxin, anticoagulant).
• Valvular surgery is indicated in moderate to severe MR if the condition becomes symptomatic.
• If the patient still has no symptoms, surgery should always be considered to treat severe structural valve disease (flail valve) if LVEF decreases to < 60% or end-systolic dimension increases to > 40(–45) mm during follow-up.
• The onset of a predisposition to AF and increased pulmonary artery pressure are also indications for surgery in an otherwise asymptomatic patient. Low operative risk and good suitability to corrective surgery are further factors supporting early surgical management of asymptomatic severe MR.
• The postoperative prognosis is very poor if the LV dysfunction is severe, and the decision to proceed with surgery must be given individual consideration even in the presence of severe symptoms.
• An attempt is usually made to treat organic MR with valve repair (valvuloplasty), in which case problems associated with long-term anticoagulation, for example, are avoided.
• If the operative risk is high, a catheter based approach (MitraClip^®) is considered to correct severe MR.

Mitral valve prolapse (MVP; Barlow syndrome)

• Prolapse of the mitral valve should be suspected if heart auscultation reveals a high-frequency mid-to-late systolic click. This finding is common (10%) and often innocent. True MVP is usually associated with pan- or late-systolic murmur of mitral regurgitation (picture /7).
• About 2% of the adult population meets the current echocardiographic criteria for true MVP. The defect is more common in patients with hereditary connective tissue diseases.
• MVP may be associated with thickening of the mitral valve cusps (at least 5 mm) signifying myxomatous degeneration.
• Significant regurgitation and/or thickening of the cusps, a floppy valve, AF and advanced age worsen the prognosis.
• Mild regurgitation may suddenly worsen dramatically as a result of chordal rupture or endocarditis.
• MVP has been thought to be associated with a slightly increased risk of disturbances in cerebral circulation.
• Echocardiography is used to assess the degree of regurgitation, the extent of cusp thickening and degeneration as well as to monitor disease progress.

Tricuspid regurgitation (TR)

• TR is almost always a consequence of pressure or volume load of the right ventricle (increased pulmonary artery pressure, atrioseptal defect, functional valvular regurgitation).
• Endocarditis associated with illicit drug use as well as iatrogenic causes (pacemaker leads, endomyocardial biopsies) are the most important causes of structural valvular regurgitation.
• Murmur
  • A pansystolic murmur which resembles the murmur of mitral regurgitation. It is best heard in the fourth intercostal space at the parasternal region. The murmur is augmented by inspiration.
  • Often soft and difficult to hear, even when the echocardiographic findings show large regurgitant flow.
• Other findings
  • Signs and symptoms of increased venous pressure
  • A prominent systolic venous pulse wave (v wave) in the neck is a typical sign.
  • Ascites, oedema, enlarged and pulsatile liver
  • Trivial regurgitation without clinical significance is frequently detected by colour Doppler echocardiography.
  • ECG and chest x-ray: hypertrophy and enlargement of the right ventricle and atrium

Diastolic murmurs

• Diastolic murmurs may either be regurgitant murmurs (aortic regurgitation) or flow murmurs (mitral stenosis).
• They invariably present pathological conditions, even if the defects were not haemodynamically significant.
• Diastolic murmurs are often soft and easily missed. The patient needs to be examined in a quiet room, and particular attention must be paid to listening during the diastole.

Aortic regurgitation (AR)

• AR may be caused by abnormalities affecting the valvular cusps or dilatation of the aortic root and annulus.
  • Atherosclerotic degeneration of the cusps and innate bicuspidal aortic valve are the most common causes of chronic regurgitation.
  • Endocarditis may cause acute worsening of AR.
  • Aortic root dilatation is often caused by connective tissue disease, and aortic dissection may cause severe acute AR.

Signs and symptoms

• AR remains asymptomatic for a long time; dyspnoea on exertion and tiredness are usually the initial symptoms.
• Massive acute MR may lead to pulmonary oedema and cardiogenic shock.
• Murmur (picture /9)
  • A diastolic, decrescendo, "sighing", blowing murmur, which is heard best with the diaphragm of the stethoscope
  • The murmur is present at the aortic area and towards the apex and is heard best if the patient leans forward and holds breath in expiration. The pitch of the regurgitant murmur is similar to that of breath sounds.
  • As the regurgitation worsens, a systolic ejection murmur will become evident as a result of increased stroke volume, even in the absence of stenosis. An early diastolic murmur usually signifies mild regurgitation and a late diastolic murmur severe regurgitation.
  • May be difficult to differentiate from breath sounds because of the high frequency.
  • The murmur becomes softer in severe AR if the patient develops heart failure.
  • Ventricular gallop (S3) is a common finding as the ventricle dilates.
• Other findings
  • Wide pulse pressure and low diastolic pressure.
  • The pulse wave is forceful and shows a rapid rise and a quick collapse.
  • The apex beat is thrusting and laterally displaced.
  • In mild to moderate AR, the ECG is generally normal, but as the condition worsens signs of LV hypertrophy will usually develop gradually.
  • If the regurgitation is significant a chest x-ray will show cardiomegaly, but in acute AR pulmonary oedema may be the only finding. Dilatation of the ascending aorta may be evident on a chest x-ray.
• Echocardiography and Doppler examination
  • Echocardiography is the key imaging study to diagnose the regurgitation and assess disease severity. More invasive investigations are only rarely required for the estimation of the regurgitant volume.
  • Echocardiography is used to evaluate not only the structure and function of the valve but also the width of the aortic root and the LV size and function.

Follow-up and management

• Severe acute AR is a life-threatening condition and urgent surgical intervention is indicated.
• ACE inhibitors or vasodilating calcium-channel blockers have been used when surgery is not recommended and, after individual consideration, to improve the patient’s haemodynamic profile before proceeding with surgery.
  • Medical therapy has also been used, after individual consideration, particularly if hypertension is a problem, even though evidence on the effect of medication on disease progress remains inconsistent.
• In significant chronic AR, surgery is indicated as soon as exertional symptoms emerge.
• Surgery is indicated for asymptomatic patients if LV dilatation is significant (end-diastolic dimension greater than 70 mm or end-systolic dimension greater than 50 mm) or signs of LV dysfunction become evident (EF decreases to < 50%)
• If the diameter of the ascending aorta increases to more than 45 mm, simultaneous aortic repair is usually indicated.
• If the diameter of the aortic root increases to 55 mm, surgical treatment is usually indicated independent of the severity of aortic regurgitation.
• In patients with a connective tissue disease (Marfan syndrome) or bicuspid aortic valve the condition of the aorta should be followed up more intensely and indications for aortic root surgery are less strict.
Drug therapy with beta blockers, ACE inhibitors and angiotensin receptor blockers appear to slow down the dilatation of the aortic root in patients with Marfan syndrome. The effect of ACE inhibitors and sartans on the aggravation of the condition is under research.
• Markedly impaired systolic function of a long duration cannot be corrected by surgery.

Systolic and diastolic murmur

Combined valvular diseases (stenosis and regurgitation within the same valve)

• Aortic and mitral stenoses do not always occur alone. A diseased stenosed valve may also leak to a variable extent with a resultant murmur during both systole and diastole.
• In aortic regurgitation, a systolic ejection murmur (usually Grade 2) caused by increased stroke volume is heard in addition to the diastolic regurgitant murmur, even if the valve is not stenotic.
• A patent ductus arteriosus and coronary artery fistula may cause a continuous systolic-diastolic murmur. The sound of pericardial rub is rhythmic and can often be heard during systole and diastole. Echocardiography is indicated if a new murmur is detected or an existing murmur changes.

Additional investigations to assess the significance of a murmur

• The differentiation between an innocent murmur and a murmur caused by a cardiac defect is a challenging task.
• An innocent murmur is typically an early-to-mid systolic, Grade 1–2 ejection murmur, heard at the apex or on the left parasternal region, intensified by a sitting up position and is not very widespread.
• Diastolic and pansystolic murmurs reflect a structural defect. If the cause and severity of the defect is not known, the patient should be referred to a cardiologist for assessment and echocardiography.
• A large share of prominent (Grade 2) and widespread murmurs are caused by a valvular disease, and echocardiography is usually indicated to establish the aetiology of the murmur.
• A murmur must always be viewed in relation to the patient’s chest (a murmur is more difficult to hear if the patient is overweight or has emphysema), symptoms (functional capacity, signs of heart failure) and overall condition (fever, dyspnoea, hypotension). Murmurs will become inaudible, even when they originate from significant valvular disease, in hypotensive patients with heart failure, and they will be masked by the crackles of pulmonary oedema.
• If a murmur strengthens or changes (a new diastolic murmur) as compared with previous auscultations or records in the patient’s notes, the condition usually needs to be reassessed and the patient warrants a new echocardiography carried out by a cardiologist.
• If a patient with a known valvular disease presents with fever, the possibility of endocarditis must always be considered.
• Likewise, a deterioration of the valvular disease must always be borne in mind if the patient complains of worsening functional capacity or a new onset dyspnoea on exertion, even if no changes can be detected during auscultation.
• Pulse, blood pressure, venous pressure, heart auscultation and the recent history of exercise capacity must always be included in routine investigations.
• ECG and chest x-ray are also routine investigations, but their value in the diagnosis of minor valvular disease and murmurs is small.
• The determination of natriuretic peptides can be carried out to eliminate heart failure. Their concentration is often slightly increased even in minor valvular disease, and the significance of changes seen in concentrations during follow-up is unclear.
• Exercise stress testing is mainly used to evaluate coexisting coronary heart disease and to obtain an objective assessment of exercise capacity when a discrepancy exists between the signs and symptoms or if the patient is normally not physically active.

Related resources

• Clinical guidelines
• Decision support
• Literature

Ədəbiyyat

1. Carabello BA. Clinical practice. Aortic stenosis. N Engl J Med 2002 Feb 28;346(9):677-82.
2. Nishimura RA, Otto CM, Bonow RO et al. 2014 AHA/ACC Guideline for the Management of Patients With Valvular Heart Disease: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. Circulation 2014;129(23):e521-643.
3. Joint Task Force on the Management of Valvular Heart Disease of the European Society of Cardiology (ESC), European Association for Cardio-Thoracic Surgery (EACTS), Vahanian A et al. Guidelines on the management of valvular heart disease (version 2012). Eur Heart J 2012;33(19):2451-96.