New heart murmur

A new heart murmur is an extra sound in the cardiac cycle, produced by turbulent blood flow, detected for the first time or changed from before. It may be innocent (flow murmur from a normal heart) or point to valve disease, a shunt, endocarditis, a post infarction complication or a high output state.

Clinical relevance. Murmurs are found in up to 50% of children and 10% of adults. Most are innocent, but pathological murmurs are an important sign of:

• valvular heart disease (aortic stenosis in 2% to 4% of those over 65)
• endocarditis
• rheumatic heart disease (still a leading cause in low income countries)
• acute mechanical complications after myocardial infarction

A new murmur with fever must prompt a search for endocarditis.

Classification by timing.

• Systolic: ejection (aortic stenosis, hypertrophic cardiomyopathy, pulmonary stenosis, flow murmurs), pansystolic (mitral regurgitation, tricuspid regurgitation, ventricular septal defect), late systolic (mitral valve prolapse).
• Diastolic: early diastolic (aortic regurgitation, pulmonary regurgitation), mid diastolic (mitral stenosis, tricuspid stenosis, Austin Flint), late diastolic (presystolic accentuation of mitral stenosis).
• Continuous: patent ductus arteriosus, arteriovenous fistula, venous hum, aortopulmonary window, coronary fistula.

Grading. Levine grade 1 (barely audible) to 6 (audible without a stethoscope); a thrill indicates grade 4 or more. Grade 3 or more, diastolic and continuous murmurs are rarely innocent.

Innocent murmur features (the 7 S's). Soft, systolic, short, sweet (musical), single (no associated sounds), small (localised), sensitive to position (changes with posture or respiration). Also normal S2, no thrill, no ejection click, no radiation, no symptoms, no abnormal ECG.

History.

• Symptoms: breathlessness, orthopnoea, fatigue, chest pain, syncope or presyncope on exertion, palpitations, oedema, reduced exercise tolerance, dizziness.
• Fever, night sweats, rigors, weight loss, malaise, joint pain, recent dental work or procedures, injecting drug use, indwelling lines, recent sore throat (streptococcal infection), previous rheumatic fever.
• Chest pain in the previous days (myocardial infarction with papillary muscle rupture or ventricular septal rupture).
• Past history: congenital heart disease, rheumatic heart disease, bicuspid aortic valve, valve surgery, prosthetic valve, previous endocarditis, hypertension, anaemia, thyroid disease, pregnancy.
• Family history of cardiomyopathy, sudden death, Marfan syndrome and bicuspid valve.
• Drugs: appetite suppressants (fenfluramine, phentermine), dopamine agonists (cabergoline, pergolide), ergotamines, methysergide, anthracyclines (valve and ventricular disease), anticoagulants.
• Cardiac history: radiotherapy to the chest, carcinoid syndrome.

Examination.

• Vital signs: temperature, pulse (rate, rhythm, character: slow rising in aortic stenosis, collapsing in aortic regurgitation, bisferiens in mixed lesions), blood pressure (narrow pulse pressure in aortic stenosis, wide in regurgitation, differential arm pressures).
• Peripheral signs of endocarditis: fever, clubbing, splinter haemorrhages, Janeway lesions, Osler nodes, Roth spots, petechiae, splenomegaly, microscopic haematuria, embolic signs; stigmata of injection.
• Jugular venous pressure (raised in right sided or biventricular failure, giant v waves in tricuspid regurgitation, prominent a waves in pulmonary stenosis).
• Palpation: apex beat (displaced, heaving, tapping, thrusting), thrills, parasternal heave.
• Auscultation:
  • heart sounds (S1 loud in mitral stenosis, S2 splitting, loud P2 in pulmonary hypertension, S3, S4)
  • added sounds (opening snap, ejection click, mid systolic click)
  • murmur characteristics: timing, location, radiation (carotids in aortic stenosis, axilla in mitral regurgitation), intensity, pitch
  • variation with respiration (right sided louder on inspiration)
  • Valsalva (hypertrophic cardiomyopathy louder, most others softer)
  • standing and squatting (hypertrophic cardiomyopathy louder on standing and softer on squatting)
  • handgrip (mitral regurgitation, aortic regurgitation and ventricular septal defect louder; hypertrophic cardiomyopathy and aortic stenosis softer)
• Lungs: crackles, wheeze; abdomen: hepatomegaly, ascites, pulsatile liver; legs: oedema.
• Signs of Marfan syndrome, thyroid disease, anaemia, pregnancy.

Red flags.

• Murmur with fever and constitutional symptoms (endocarditis).
• Murmur after myocardial infarction with new shock, pulmonary oedema (acute mitral regurgitation, ventricular septal rupture).
• Syncope, angina or exertional breathlessness with an ejection systolic murmur (severe aortic stenosis).
• Murmur with heart failure signs, new atrial fibrillation or embolic event.
• New regurgitant murmur with prosthetic valve (dehiscence, thrombosis, endocarditis).
• Diastolic or continuous murmur, grade 3 or more, thrill, or abnormal heart sounds.
• Murmur with cyanosis, clubbing or failure to thrive.
• Tearing chest pain with new aortic regurgitation (dissection).
• Recent streptococcal sore throat, migratory arthritis, chorea, carditis (rheumatic fever).
• Family history of sudden death with systolic murmur that increases on standing (hypertrophic cardiomyopathy).

Innocent and physiological. Still murmur in children, pulmonary flow murmur, venous hum, supraclavicular arterial bruit, flow murmur of pregnancy, anaemia, fever, thyrotoxicosis, exercise, athletes, high output states (beriberi, Paget disease, arteriovenous fistula), and aortic sclerosis in older adults.

Systolic murmurs.

• Aortic stenosis (calcific, bicuspid, rheumatic).
• Hypertrophic obstructive cardiomyopathy, subvalvular and supravalvular stenosis, pulmonary stenosis.
• Mitral regurgitation (degenerative prolapse, rheumatic, ischaemic, endocarditis, functional from dilated ventricle, papillary muscle rupture).
• Tricuspid regurgitation (endocarditis in injecting drug users, pulmonary hypertension, carcinoid, Ebstein anomaly).
• Ventricular septal defect (congenital, post infarction).
• Atrial septal defect with pulmonary flow murmur, and coarctation.

Diastolic murmurs.

• Aortic regurgitation (bicuspid valve, rheumatic, endocarditis, dissection, aortic root dilatation in Marfan syndrome, syphilis, ankylosing spondylitis).
• Mitral stenosis (rheumatic) and tricuspid stenosis.
• Pulmonary regurgitation (pulmonary hypertension, after tetralogy repair).
• Austin Flint murmur.
• Atrial myxoma (tumour plop with mid diastolic murmur).
• Left to right shunts with increased flow.

Continuous murmurs. Patent ductus arteriosus, coronary arteriovenous fistula, ruptured sinus of Valsalva aneurysm, systemic arteriovenous fistula, venous hum, pulmonary arteriovenous malformation, aortopulmonary window.

Infective and inflammatory causes of a new murmur. Infective endocarditis (native and prosthetic valve), acute rheumatic fever (carditis with mitral regurgitation, Carey Coombs murmur), myocarditis, Libman-Sacks endocarditis in lupus, marantic endocarditis, Kawasaki disease, pericarditis (rub, not a murmur).

Ischaemic complications. Papillary muscle dysfunction or rupture (acute mitral regurgitation), ventricular septal rupture, free wall rupture, left ventricular aneurysm.

1. Decide which murmurs need no investigation. An asymptomatic patient with a grade 1 to 2 mid systolic murmur, normal heart sounds, no radiation, no thrill, no abnormal signs and a normal ECG can be observed (innocent murmur, aortic sclerosis).
2. 12 lead ECG (hypertrophy, strain, atrial enlargement, atrial fibrillation, conduction defects, ischaemia, pre-excitation) and chest radiograph (heart size, pulmonary congestion, valve calcification, aortic dilatation).
3. Echocardiography (transthoracic) for every patient with symptoms, diastolic or continuous murmurs, grade 3 or more systolic murmurs, murmurs with abnormal signs or ECG, new murmurs with fever or after infarction. It assesses:
   • valve anatomy and severity (aortic stenosis: peak velocity over 4 m/s, mean gradient 40 mmHg or more, valve area under 1.0 cm2, severe; mitral regurgitation: effective regurgitant orifice 0.4 cm2 or more)
   • left ventricular size and function
   • pulmonary pressure, shunts, vegetations, pericardial fluid
4. Transoesophageal echocardiography for suspected endocarditis with a negative or inconclusive transthoracic study, prosthetic valves, abscess and acute mitral regurgitation.
5. Blood tests: full blood count, ESR, C reactive protein, urea, creatinine, electrolytes, thyroid function, glucose, troponin and natriuretic peptide as indicated.
6. Suspected endocarditis:
   • at least three sets of blood cultures from separate venepunctures taken before antibiotics (at least one hour apart in stable patients; in acute illness three sets within 1 hour)
   • urinalysis, rheumatoid factor and complement
   • serology for Coxiella, Bartonella, Brucella and fungi when culture negative
   • apply the modified Duke criteria
   • CT, MRI or PET for embolic and perivalvular disease
7. Suspected rheumatic fever: throat swab and anti streptolysin O and anti DNase B titres, modified Jones criteria, and echocardiography.
   • Major criteria: carditis, polyarthritis, chorea, erythema marginatum, subcutaneous nodules.
   • Minor criteria: fever, arthralgia, raised ESR and C reactive protein, prolonged PR interval.
   • Evidence of preceding streptococcal infection.
8. Exercise testing or dobutamine stress echocardiography for low flow, low gradient aortic stenosis, or to assess symptoms. CT calcium score of the aortic valve. Cardiac CT, MRI and catheterisation for severity, aortic root and coronary assessment before surgery.
9. Genetic and family screening for hypertrophic cardiomyopathy, bicuspid aortic valve and aortopathy.
10. Right heart catheterisation when pulmonary hypertension or shunts are suspected.

Limits.

• Intensity does not reliably correlate with severity (low flow aortic stenosis can be quiet; acute severe regurgitation can have a short soft murmur).
• Murmurs are absent in some severe lesions (acute aortic regurgitation, large ventricular septal rupture with equalised pressures).
• Examiner agreement is moderate; echocardiography is required for diagnosis when there is any doubt.

Emergencies.

• Acute mitral regurgitation, ventricular septal rupture or acute aortic regurgitation with shock: sit upright, give oxygen, obtain intravenous access, and call urgent cardiology and cardiac surgery. Drug options:
  • furosemide 40 to 80 mg intravenously
  • glyceryl trinitrate infusion 10 to 200 micrograms/minute if systolic pressure over 100 mmHg
  • sodium nitroprusside 0.25 to 0.5 micrograms/kg/minute titrated for afterload reduction
  • inotropes (dobutamine 2.5 to 10 micrograms/kg/minute)
  • intra aortic balloon pump as a bridge to surgery
  Avoid beta blockers and vasoconstrictors in acute aortic regurgitation.
• Infective endocarditis with heart failure or haemodynamic instability: urgent echocardiography, antibiotics and early surgery.
• Aortic dissection with new regurgitation: emergency surgery; control heart rate and blood pressure.

Infective endocarditis (suspected or proven).

• After blood cultures, start empirical antibiotics at once in an unwell patient.
  • Native valve, community acquired: amoxicillin 2 g intravenously every 4 hours plus gentamicin 1 mg/kg intravenously every 12 hours (or ceftriaxone 2 g daily), with flucloxacillin 2 g every 4 to 6 hours when Staphylococcus aureus is likely (injecting drug use, skin source).
  • Penicillin allergy or MRSA risk: vancomycin 15 to 20 mg/kg every 8 to 12 hours (trough 15 to 20 mg/L) with gentamicin.
  • Prosthetic valve or early onset: vancomycin plus gentamicin plus rifampicin 300 to 600 mg every 12 hours (start rifampicin after 3 to 5 days of effective antibiotic therapy).
• Directed therapy and duration (4 to 6 weeks of intravenous treatment, prosthetic valve at least 6 weeks):
  • viridans streptococci: benzylpenicillin 1.2 to 2.4 g every 4 hours or ceftriaxone 2 g daily for 4 weeks
  • Staphylococcus aureus: flucloxacillin 2 g every 4 to 6 hours for 4 to 6 weeks (vancomycin if MRSA)
  • Enterococcus: amoxicillin 2 g every 4 hours with gentamicin (or ceftriaxone 2 g every 12 hours with amoxicillin) for 4 to 6 weeks
• Surgery indications: heart failure from valve dysfunction, uncontrolled infection (abscess, persistent bacteraemia over 5 to 7 days, resistant organism, fungal), and large vegetations (over 10 mm) with embolism. Operate early, within the same admission, for these.
• Monitor temperature, C reactive protein, gentamicin levels (peak under 10 mg/L, trough under 1 mg/L), creatinine, hearing and balance. Use ECG for new PR prolongation (aortic root abscess) and weekly echocardiography when needed. Arrange dental review and source control.
• Prophylaxis (prevent infection) is for the highest risk patients only (prosthetic valve or material, previous endocarditis, cyanotic congenital heart disease, repaired congenital disease with residual shunt or within 6 months of device), before dental procedures that manipulate gingival tissue. Give amoxicillin 2 g orally 30 to 60 minutes before (clindamycin 600 mg or azithromycin 500 mg if penicillin allergic). Good dental hygiene for all.

Acute rheumatic fever.

• Bed rest for carditis.
• Eradicate the organism with benzathine benzylpenicillin 1.2 million units intramuscularly once (600,000 units if under 27 kg) or phenoxymethylpenicillin 500 mg twice daily for 10 days.
• Aspirin 80 to 100 mg/kg/day in 4 divided doses (maximum 4 to 8 g daily) for arthritis and mild carditis. For severe carditis use prednisolone 1 to 2 mg/kg daily (maximum 60 mg), tapered over 2 to 3 weeks.
• Heart failure drugs. For chorea: valproate 15 to 20 mg/kg/day or carbamazepine.
• Secondary prophylaxis: benzathine benzylpenicillin 1.2 million units intramuscularly every 3 to 4 weeks (or phenoxymethylpenicillin 250 mg twice daily; erythromycin 250 mg twice daily if allergic). Duration is 5 years or until age 21 for rheumatic fever without carditis, 10 years or until age 21 for carditis with resolved valve disease, and until age 40 or lifelong for persistent valve disease.

Valve disease management.

• Aortic stenosis: avoid strenuous exertion in severe disease; treat hypertension and heart failure cautiously (ramipril 1.25 to 2.5 mg, titrate); avoid vasodilator overload. Surgical or transcatheter valve replacement is indicated for:
  • symptomatic severe stenosis
  • severe asymptomatic stenosis with reduced ejection fraction (under 50%), abnormal exercise test or very high gradient
  • when other cardiac surgery is done
• Aortic regurgitation: ACE inhibitor or amlodipine, treat hypertension (systolic under 140 mmHg), and operate for symptoms, ejection fraction 55% or less, or end systolic diameter over 50 mm (25 mm/m2). Avoid beta blockers in severe acute disease.
• Mitral regurgitation: diuretics (furosemide 20 to 80 mg), ACE inhibitor, beta blocker, and treat atrial fibrillation (rate control and anticoagulation). Repair or replace for symptoms, ejection fraction 60% or less, end systolic diameter 40 mm or more, atrial fibrillation or pulmonary hypertension. Transcatheter edge to edge repair in selected patients.
• Mitral stenosis: rate control (bisoprolol 2.5 to 10 mg daily, or diltiazem), diuretics, anticoagulation with warfarin (INR 2.0 to 3.0) for atrial fibrillation or embolism, balloon valvotomy, or surgery; secondary rheumatic prophylaxis.
• Hypertrophic cardiomyopathy: beta blocker (metoprolol succinate 50 to 200 mg daily), verapamil, disopyramide 100 to 250 mg twice daily, mavacamten 2.5 to 5 mg daily (specialist). Avoid vasodilators, dehydration and strenuous exercise. Septal reduction therapy; implantable cardioverter defibrillator by risk assessment.
• Ventricular septal defect, patent ductus arteriosus and atrial septal defect: cardiology referral, closure when haemodynamically significant (device or surgery).
• Pulmonary stenosis: balloon valvuloplasty for symptomatic or gradient over 50 mmHg.
• Tricuspid regurgitation: diuretics, treat cause, surgery or transcatheter repair. Endocarditis in injecting drug users is treated with the endocarditis antibiotic regimens plus addiction support.
• Anticoagulation for mechanical valves: warfarin (INR 2.5 to 3.5 for mechanical mitral valve, 2.0 to 3.0 for mechanical aortic valve without risk factors). Direct oral anticoagulants are not used in mechanical valves or moderate to severe mitral stenosis. Bioprosthetic valves take antiplatelet or direct oral anticoagulants depending on rhythm.

Innocent murmur and flow murmur. Reassure; no restriction of activity or investigations once echocardiography confirms normality where indicated. Treat the high output cause (anaemia: iron, thyroid disease, fever, pregnancy).

Monitoring.

• Symptoms and examination at each review.
• Echocardiography every 3 to 5 years for mild, 1 to 2 years for moderate and every 6 to 12 months for severe asymptomatic valve disease.
• ECG; weight and fluid status; INR for warfarin; dental review every 6 months.
• Follow up after endocarditis: echocardiography at end of treatment, 3, 6 and 12 months.

Referral and escalation. Cardiology for all pathological murmurs and for symptomatic, severe or unexplained murmurs. Cardiac surgery or structural heart team for valve intervention. Infectious diseases for endocarditis. Paediatric cardiology for children. Obstetric cardiology for pregnancy. Rheumatology for lupus. Genetics for hypertrophic cardiomyopathy and connective tissue disease.

Admission. Suspected endocarditis, acute valve failure, heart failure, syncope, post infarction murmur, new arrhythmia, embolic events, acute rheumatic fever with carditis, or haemodynamic instability.

Safety netting. Return at once for fainting, chest pain, breathlessness at rest, swelling, fever or rigors, new rashes, weakness on one side, severe headache, or vision loss. Keep good dental hygiene, report fever after dental work, finish all antibiotic courses and attend echocardiography follow up.

Special groups.

• Pregnancy: flow murmurs are common; stenotic lesions (mitral stenosis, aortic stenosis) are poorly tolerated. Avoid ACE inhibitors, angiotensin receptor blockers and warfarin in the first trimester (use enoxaparin 1 mg/kg twice daily for mechanical valves with anti Xa monitoring). Balloon valvotomy is possible.
• Children: most murmurs are innocent; congenital lesions, rheumatic fever and Kawasaki disease need assessment.
• Older adults: calcific aortic stenosis and mitral annular calcification predominate.
• Athletes: flow murmurs are common; exertional symptoms need echocardiography before sport.
• Injecting drug users: right sided endocarditis with septic pulmonary emboli.
• Endemic regions: rheumatic heart disease is the leading cause in young adults. Screen with echocardiography in endemic areas and provide secondary prophylaxis. Chagas disease, syphilitic aortitis, endomyocardial fibrosis, tuberculous pericarditis and HIV related cardiomyopathy contribute.