GC050 Fever And A Murmur
A clinical presentation of fever accompanied by a cardiac murmur, raising concern for infective endocarditis until proven otherwise.
Fever and a Heart Murmur: Valvular Heart Diseases & Infective Endocarditis
This lecture by Professor Kai-Hang Yiu covers three major areas [1]:
- Common valvular heart diseases — mitral stenosis (MS), mitral regurgitation (MR), mitral valve prolapse (MVP), aortic stenosis (AS), aortic regurgitation (AR), and tricuspid regurgitation (TR)
- Infective endocarditis (IE) — pathogenesis, clinical features, diagnosis (Modified Duke criteria), microbiology, treatment principles, and surgical indications
- New guidelines for IE prophylaxis — which patients, which procedures, and why the guidelines were revised
The big idea: A patient presenting with fever and a new or changing murmur should trigger immediate consideration of infective endocarditis — a potentially fatal but curable infection. However, to recognise a "changing murmur" or to identify IE's predisposing conditions, you must first understand the underlying valvular lesion. This lecture therefore pairs valvular disease with IE as two sides of the same clinical coin.
How this fits exams: HKUMed summatives frequently test Modified Duke criteria, the organisms causing IE, antibiotic prophylaxis indications, and the auscultatory/clinical findings of each valve lesion. The Cardiology Interactive Tutorial (Case 1) uses a near-identical clinical scenario — a 50-year-old man with MVP, fever, and IE [2].
Valvular stenosis → hypertrophy of the proximal (upstream) chamber; as it fails, dilatation occurs. Valvular regurgitation → dilatation of chambers on either side of the valve. [1]
Why this matters from first principles:
- Stenosis creates a pressure overload. The chamber upstream must generate higher pressures to push blood through a narrowed orifice. The myocardium responds with concentric hypertrophy (adding sarcomeres in parallel). Eventually the wall stiffens, filling pressures rise, and the chamber dilates — marking the onset of failure.
- Regurgitation creates a volume overload. Blood leaks backward, so the upstream chamber receives its normal venous return plus the regurgitant volume. Both the upstream and downstream chambers handle larger volumes, leading to eccentric dilatation (sarcomeres in series). Initially the heart compensates by increasing stroke volume; eventually the muscle stretches beyond optimal Frank–Starling range and fails.
This simple framework lets you predict symptoms (back-pressure → congestion; forward-failure → low output) and signs (chamber enlargement patterns on ECG/CXR/echo) for every valve lesion.
1. Left heart failure — progressive exertional dyspnoea; 2. Right heart failure — ankle oedema, hepatic pain; 3. Chest pain — myocardial ischaemia; 4. Palpitations — commonly AF; 5. Low output — easy fatigability; 6. Complications: (a) thromboembolism, (b) infective endocarditis, (c) problems during pregnancy. [1]
High Yield — Complications of Valvular Disease
Thromboembolism (especially with AF in mitral disease), infective endocarditis, and haemodynamic decompensation in pregnancy are the three key complications examiners love to ask about. Pregnancy increases intravascular volume by ~30%, which can unmask or acutely worsen MS.
1. ECG — chamber enlargement, AF; 2. CXR; 3. Echocardiogram — valvular architecture, chamber size, chamber function, Doppler (gradient/regurgitation), low-dose dobutamine for ischaemia and contractile reserve; 4. Exercise testing — objective functional capacity; 5. Cardiac catheterisation — associated CAD, pressure gradient, contrast injection for regurgitant lesions. [1]
- Echocardiography is the single most important investigation for valvular disease. It directly visualises the valve anatomy, quantifies severity (gradients, orifice area, regurgitant volume), and assesses ventricular function.
- Cardiac catheterisation is now primarily for assessing concomitant coronary artery disease pre-operatively, not for diagnosing the valve lesion itself.
Commonest valvular involvement: Mitral > Aortic + Mitral > Aortic > Tricuspid. For mitral valve: MS > MR + MS > MR. [1]
Why mitral valve is most affected: The mitral valve endures the highest haemodynamic stress (left-sided, high pressure, large excursion). Rheumatic inflammation causes commissural fusion (stenosis) and leaflet retraction/chordal shortening (regurgitation). The aortic valve is second because it also faces high pressure. The tricuspid is rarely involved in isolation because right-sided pressures are lower.
The Jones criteria for acute rheumatic fever (2 major or 1 major + 2 minor, plus evidence of recent GAS infection) and secondary prophylaxis with IM benzathine penicillin G are essential background [3].
Mitral Stenosis (MS)
95% rheumatic; 5% congenital (RARE) [1]
Obstruction to LV inflow → ↑LA pressure → ↑pulmonary venous pressure → ↑thickness of pulmonary vascular beds → pulmonary arterial hypertension ("second stenosis") → right heart failure. [1]
From first principles: The stenotic mitral valve acts like a dam between the LA and LV. Blood backs up into the LA, then into the pulmonary veins, then the pulmonary capillaries (causing oedema), and eventually the pulmonary arteries remodel (reactive pulmonary hypertension = "second stenosis"). This irreversible pulmonary vascular change further burdens the right ventricle, which eventually fails.
1. Respiratory symptoms — SOB on exertion, PND; 2. Chronic RV failure — congestive cardiac failure; 3. Atrial fibrillation — 50–75% of MS patients develop AF because of ↑LA size; AF is an important cause of cardiac decompensation because: (a) normal LA contraction contributes 20% of LV filling, which becomes more important in MS ("atrial kick"), (b) ↑ventricular rate reduces diastolic filling time, reducing SV and CO; 4. Systemic embolisation — LA enlarged leading to stasis of blood. [1]
High Yield — Why AF Causes Decompensation in MS
In MS, diastolic filling time is critical because blood must cross a narrowed valve. AF causes two problems simultaneously: (1) loss of the atrial kick (20% of LV filling), and (2) fast ventricular rate shortening diastole. This is why rate control is paramount in MS with AF — even more so than in other conditions.
Mechanism of AF in MS (from senior notes [4]): LA dilatation distorts the pulmonary vein–LA junction. Micro-reentrant circuits develop in the dilated, stretched atrial tissue, initiating and sustaining AF.
Malar flush (pulmonary hypertension); (1) Pulse — small volume, irregular if in AF; (2) Venous — loss of 'a' wave in AF, ↑JVP if RHF; (3) Precordium — parasternal heave / tapping apex, loud S1, opening snap (OS), mid-diastolic rumbling murmur (may be enhanced with exercise, lying on left side); (4) Signs of complications — pulmonary oedema, embolisation (peripheral vessels, stroke). [1]
| Sign | Explanation |
|---|---|
| Malar flush | Low cardiac output + chronic hypoxaemia → cutaneous vasodilation over cheeks |
| Tapping apex | Palpable loud S1 (forceful valve closure from high LA-LV gradient) |
| Parasternal heave | RV hypertrophy from pulmonary hypertension (also pushed forward by large LA) |
| Loud S1 | Valve leaflets are wide apart at end-diastole (high LA pressure keeps them open), then slam shut forcefully at onset of systole |
| Opening snap (OS) | Rigid but still mobile valve snaps open when LA pressure exceeds LV diastolic pressure |
| Mid-diastolic rumble | Turbulent flow through narrowed mitral orifice during passive ventricular filling |
Clinical severity indicators:
Duration of murmur; Interval between S2 and OS [1]
- A shorter S2–OS interval means higher LA pressure (valve opens sooner) = more severe MS.
- A longer murmur duration means significant gradient persists through more of diastole = more severe MS.
CXR: ↑LA (straight left heart border), pulmonary oedema, Kerley A and B lines. ECG: if sinus — P mitrale (bifid P wave); AF; RVH. Echo: thickened + doming leaflets, parallel diastolic movement of MV, measure MV opening (significant MS if < 1.5 cm²). Cardiac catheterisation: unnecessary if pure MS; to assess associated CAD. [1]
| Investigation | Key finding | Significance |
|---|---|---|
| CXR | Straightened left heart border | LA appendage enlargement |
| CXR | Kerley B lines | Interstitial pulmonary oedema (thickened interlobular septa) |
| ECG | Bifid P wave (P mitrale) | LA enlargement (> 120 ms) |
| Echo | MVA < 1.5 cm² | Significant MS |
| Echo | Doming leaflets | Commissural fusion (rheumatic) |
1. Diuretics; 2. Rate control if in AF; 3. Anticoagulation (valvular AF) — warfarin. Indications: history of embolisation, paroxysmal or sustained AF. [1]
High Yield — Warfarin in Valvular AF
Valvular AF (i.e., AF associated with moderate-to-severe MS or a mechanical prosthetic valve) is an absolute indication for warfarin. NOACs (DOACs) are NOT recommended for valvular AF. This is a commonly tested distinction.
1. Percutaneous balloon valvuloplasty; 2. Valvotomy (closed or open); 3. MVR — if valve calcified or badly destroyed. [1]
Balloon valvuloplasty is the procedure of choice for patients with pliable, non-calcified valves with minimal MR and no LA thrombus.
1. Atrial fibrillation; 2. Chest infection; 3. Pregnancy — ↑intravascular volume by 30%. [1]
Mitral Regurgitation (MR)
1. Rheumatic — 50% associated with MS; 2. Mitral valvular prolapse; 3. Ruptured chordae tendinae — degenerative/collagen disease (e.g., Marfan's), IE, active rheumatic heart disease; 4. Papillary muscle dysfunction — ischaemia or MI; 5. LV dilatation — enlarged MV ring leading to regurgitation. [1]
Causes 1–3 are primary (organic) MR — the valve apparatus itself is diseased. Causes 4–5 are secondary (functional) MR — the valve is structurally normal but doesn't coapt properly because the ventricle is dilated or ischaemic. This distinction matters for treatment: primary MR is fixed by repairing/replacing the valve; secondary MR is addressed by treating the underlying LV dysfunction.
↑LA pressure only during systole, ∴ pulmonary hypertension usually a late feature. Volume overload of LV can lead to LV enlargement and failure. Acute rupture of chordae → acute LV failure because LV has no time to adapt to the increased volume. [1]
Why pulmonary HTN is late in MR but early in MS: In MS, the LA pressure is elevated continuously (obstruction is constant throughout diastole). In MR, the LA receives the regurgitant jet only during systole; during diastole the LA decompresses forward into the LV. Hence the mean LA pressure rises more slowly, and the pulmonary vasculature has time to adapt. In acute MR (e.g., chordal rupture), there is no time for LA compliance to increase, so LA pressure skyrockets suddenly → flash pulmonary oedema.
LV dilatation; S1 not increased; S2 obscured by murmur; S3 usual; pansystolic murmur radiating to axilla. [1]
| Feature | Reason |
|---|---|
| Displaced apex | LV dilatation from volume overload |
| S3 | Rapid LV filling in early diastole (volume overload) |
| Pansystolic murmur → axilla | Regurgitation occurs throughout systole; jet directed posterolaterally toward the axilla |
CXR: LV enlargement. Echo: define cause of MR. Cardiac catheterisation: assess severity, associated CAD. [1]
1. If symptomatic → repair or MVR; 2. Asymptomatic: ↑heart size or ↓LV function → consider surgery; 3. Functional MR, poor LV and refractory HF. [1]
Repair is preferred over replacement because it preserves the subvalvular apparatus (chordae + papillary muscles) which is critical for LV geometry and function. Transcatheter edge-to-edge repair (MitraClip) is an option for high-risk surgical candidates [1].
Systolic prolapse of MV into LA. May be isolated or associated with secundum ASD, Turner's syndrome, PDA, Wolff-Parkinson-White syndrome. Clinical features: asymptomatic, atypical chest pain, palpitation, mid-systolic click(s) and late systolic murmur (accentuated by standing). Complications: (1) progressive severe MR requiring MVR, (2) emboli, (3) AF. [1]
Why standing accentuates the click/murmur: Standing decreases venous return → smaller LV cavity → the prolapsing leaflet reaches its prolapse point earlier in systole → the click occurs earlier and the murmur lasts longer. Squatting does the opposite (increases venous return → larger LV → later click, shorter murmur). This is a classic exam trick.
Aortic Stenosis (AS)
Rheumatic — often associated with MS. Non-rheumatic — congenital (bicuspid), subvalvular, supravalvular, calcific. By age: < 60 rheumatic or congenital (bicuspid/unicuspid); 60–75 calcified bicuspid valve (usually male); > 75 degenerative calcification (usually female). [1]
Gradient develops across AV obstructing aortic outflow. Compensatory LVH (no cavity dilatation until HF develops). Inadequate increase in CO during exercise. Severe AS = AV area < 1 cm² and/or mean pressure gradient > 50 mmHg (lower in HF). [1]
Why LVH develops without dilatation initially: Pressure overload triggers concentric hypertrophy — new sarcomeres are laid in parallel to generate more wall tension to overcome the high afterload. The cavity stays the same size or even shrinks. This is in contrast to volume overload lesions (MR, AR) where the cavity dilates.
Why gradient may be low in HF: If the LV is failing and can't generate adequate flow, the transvalvular gradient will be deceptively low despite severe stenosis. This is "low-flow, low-gradient AS" — echocardiography with low-dose dobutamine can unmask the true severity by increasing flow and revealing the gradient.
1. Exertional dyspnoea; 2. Angina pectoris; 3. Congestive cardiac failure. When AS becomes symptomatic, mortality 50% in 3 years. 4. Syncope or sudden death. [1]
High Yield — Prognosis of Symptomatic AS
The classic triad of symptomatic AS is angina, syncope, and heart failure. Once symptoms appear, survival without surgery is: angina ~5 years, syncope ~3 years, heart failure ~2 years. "Mortality 50% in 3 years" after symptom onset — this is the single most important prognostic fact for AS. Symptomatic AS is an indication for urgent valve replacement.
Why angina occurs without CAD in AS: The massively hypertrophied LV has increased myocardial oxygen demand. Simultaneously, the elevated LV end-diastolic pressure compresses subendocardial coronary vessels during diastole, reducing coronary perfusion. Supply-demand mismatch → angina.
Why syncope occurs: During exercise, peripheral vasodilation lowers SVR, but the fixed obstruction prevents the necessary increase in cardiac output. Blood pressure drops → cerebral hypoperfusion → syncope. Arrhythmias (from the hypertrophied myocardium) can also cause syncope.
Slow-rising pulse; LVH; ↓A2 (if calcified and severely stenotic); thrill + ejection systolic murmur at aortic area, radiating to neck. [1]
| Sign | Mechanism |
|---|---|
| Slow-rising (pulsus tardus) / low-volume (pulsus parvus) pulse | Obstruction slows and reduces aortic flow |
| Diminished A2 | Calcified, immobile valve cusps can't "snap" shut |
| Ejection systolic murmur → carotids | Turbulence across the narrowed AV; directed up the aorta to neck vessels |
| Systolic thrill | Palpable turbulence (grade ≥ 4 murmur) |
Aortic Regurgitation (AR)
1. Rheumatic; 2. Non-rheumatic: IE (diseased or normal valve as in drug addicts), syphilis (dilatation of aortic ring), congenital (Marfan's, congenital bicuspid valve), seronegative rheumatoid (ankylosing spondylitis, Reiter's, psoriatic arthropathy), traumatic (aortic dissection, ruptured sinus of Valsalva, external trauma). [1]
Causes can be broadly divided into valve leaflet disease (rheumatic, IE, bicuspid) and aortic root dilatation (Marfan's, syphilis, dissection, seronegative arthropathies). This distinction matters because root dilatation often requires composite graft repair (valve + ascending aorta), not just valve replacement.
Regurgitant volume → ↑LVEDV (with initially normal LVEDP). ↑SV in compensated case by LV dilatation. Deterioration of LV function → ↑LVEDP → SOB + heart failure → early mitral valve closure. Impaired LV function → ↓SV. [1]
Why symptoms are similar to AS: Both lesions ultimately lead to LV failure. In AS, it's pressure overload; in AR, it's volume overload. Both cause exertional dyspnoea, angina (in AR, the low diastolic pressure reduces coronary perfusion), and syncope.
1. Collapsing pulse (pulse pressure > 50 mmHg); 2. LV dilatation; 3. Early blowing diastolic murmur following S2. [1]
1. Austin-Flint murmur — diastolic murmur across MV (AR jet impinges on anterior mitral leaflet); 2. Duroziez sign — to-and-fro murmur over femoral arteries; 3. Quincke's pulse — capillary pulsation in fingertips or mucous membranes; 4. Traube's sign — pistol-shot (systolic and diastolic) sounds over femoral artery; 5. De Musset's sign — head bobbing with each heartbeat; 6. Corrigan's pulse — rapid upstroke and collapse of carotid artery. [1]
All these signs reflect the wide pulse pressure (high systolic from large stroke volume + low diastolic from regurgitation back into LV). The greater the pulse pressure, the more dramatic the peripheral signs.
Exam Tip — AR Eponyms
You don't need to recite all of these for marks, but the top three to know are: collapsing/water-hammer pulse, Austin-Flint murmur, and Quincke's sign. Corrigan's pulse is also commonly tested in clinical exams.
Causes: functional (right heart failure) — most common; IE; rheumatic; infiltrative. Signs: pulsatile liver, giant V wave in JVP, pansystolic murmur over lower sternal border (↑ with inspiration — Carvallo's sign), RV heave, cardiac cirrhosis. Treatment: bed rest, diuretics + spironolactone, valvuloplasty. [1]
Why the murmur increases with inspiration: Inspiration increases venous return to the right heart, increasing the volume of regurgitant flow across the tricuspid valve → louder murmur. This is Carvallo's sign and helps distinguish TR murmur from MR murmur.
Pulsatile liver: Systolic regurgitation transmits a pressure wave retrograde through the IVC and hepatic veins into the liver. Chronic TR leads to hepatic congestion → "cardiac cirrhosis."
This slide [1] compares the two main prosthetic options:
| Feature | Mechanical Valve | Bioprosthetic Valve |
|---|---|---|
| Durability | Lifelong (> 25 years) | Limited (10–20 years, earlier degeneration in younger patients) |
| Anticoagulation | Lifelong warfarin (INR 2.5–3.5 for mitral; 2.0–3.0 for aortic) | Short-term only (3–6 months, then aspirin) |
| Risk of thromboembolism | Higher if inadequate anticoagulation | Lower |
| Typical candidate | Younger patients, good compliance, no contraindication to warfarin | Older patients ( > 65–70), contraindication to warfarin, women of childbearing age (warfarin is teratogenic) |
| Sound | Audible metallic click | Silent |
| Valve Lesion | Murmur | Best heard | Key physical signs | Key Ix finding |
|---|---|---|---|---|
| MS | Mid-diastolic rumble + OS | Apex (left lateral) | Malar flush, tapping apex, loud S1, parasternal heave | MVA < 1.5 cm², P mitrale on ECG |
| MR | Pansystolic | Apex → axilla | Displaced apex, S3 | LA/LV dilatation |
| MVP | Mid-systolic click + late systolic murmur | Apex | Accentuated by standing | Prolapsing leaflet on echo |
| AS | Ejection systolic | Aortic area → neck | Slow-rising pulse, thrill, ↓A2 | AVA < 1 cm², mean gradient > 50 mmHg |
| AR | Early diastolic blowing | Left sternal border (lean forward, end-expiration) | Collapsing pulse, wide PP, De Musset's | LV dilatation, diastolic flow reversal |
| TR | Pansystolic | Lower LSB (↑inspiration) | Giant V wave, pulsatile liver, RV heave | RV dilatation |
Infective Endocarditis (IE)
A disease caused by microbial infection of the endocardial lining of the heart (or blood vessels). [1]
Valvular: MR > MS, AR > AS; prosthetic valves; normal valves in IV drug addicts. Shunts: congenital or post-surgical (VSD, PDA, AV fistula). [1]
Why regurgitant lesions predispose more than stenotic lesions: Regurgitant jets create high-velocity flow that damages the endothelium on the low-pressure side of the valve. This damaged endothelium accumulates fibrin and platelets (non-bacterial thrombotic endocarditis / NBTE), which serves as a nidus for bacterial colonisation during transient bacteraemia. Stenotic valves, while damaged, have less jet-stream endothelial injury.
Why IV drug users get IE on normal valves: Injected particulate matter and bacteria directly enter the venous circulation → right-sided endocarditis (typically tricuspid). The repeated endothelial trauma from injected material provides a nidus even without pre-existing valve disease. Staph. aureus is the most common organism [1].
Clinical features of IE are classified into: (A) Systemic infection, (B) Manifestations of intravascular lesions, (C) Manifestations of immunological reactions. [1]
| Category | History | Examination | Investigation |
|---|---|---|---|
| A. Systemic infection | Fever, chills, rigors (highly variable) | Fever, pallor, weight loss, splenomegaly | Anaemia, leucocytosis, ↑ESR, blood culture positive |
| B. Intravascular lesions | Chest pain, heart failure, embolism (stroke, cold limbs) | Changing murmurs, signs of HF, petechiae, Roth spots, Osler's nodes, Janeway lesions, splinter haemorrhages | RBC in urine, CXR, echocardiography, arteriography |
| C. Immunological reactions | Arthralgia, myalgia, tenosynovitis, GN | Arthritis, uraemia, vascular phenomena, finger clubbing | Proteinuria, casts, polyclonal Ig, ↑RF, ↓complements, immune complexes |
Janeway lesions — macular, non-painful, erythematous, on palms and soles. Osler's nodes — tender papulopustules on the pulp of the finger. [1]
High Yield — Janeway vs. Osler
A very common exam trap: Janeway = painLESS (septic micro-emboli); Osler = painFUL (immune complex deposition). Mnemonic: "Osler's nodes are Oh-so-painful" or "Janeway = J for Just painless."
| Feature | Janeway Lesion | Osler's Node |
|---|---|---|
| Pain | Painless | Painful |
| Appearance | Flat, erythematous macule | Raised, red, tender papule |
| Location | Palms and soles | Finger pulps, toes |
| Pathogenesis | Septic microemboli | Immune complex deposition |
| Duke criterion | Vascular phenomenon | Immunological phenomenon |
Other signs:
- Splinter haemorrhages — linear dark streaks in the nail bed (micro-emboli to nail bed capillaries)
- Roth spots — retinal haemorrhages with a pale centre (immune complex vasculitis of retinal vessels)
- Petechiae — conjunctival, oral mucosa, skin (micro-emboli)
1. Clinical features; 2. Blood cultures — 3 venous cultures taken at different sites and separated by at least half an hour; 3. Echocardiograms — vegetations; TOE better delineation of vegetation. [1]
Why 3 sets at different times? To demonstrate persistent bacteraemia (not transient contamination) and to maximise sensitivity. Different sites reduce the chance that a positive culture is from skin contamination at one puncture point.
TTE vs. TOE: Transthoracic echo (TTE) has ~60–70% sensitivity for vegetations. Transoesophageal echo (TOE) has ~90–95% sensitivity because the oesophageal probe is physically closer to the heart (especially the mitral and aortic valves) without lung/rib interference. TOE is mandatory for prosthetic valve endocarditis and whenever TTE is negative but clinical suspicion is high [1].
Definite IE: 2 major, or 1 major + 3 minor, or 5 minor. Pathologic criteria: (1) microorganisms demonstrated in a vegetation, (2) pathologic lesions confirmed by histology. [1]
| Major Criteria | Minor Criteria |
|---|---|
| 1. Blood culture: persistent bacteraemia of typical organisms ( > 2/3 positive) | 1. Predisposing lesion or IV drug use |
| 2. Evidence of endocardial involvement: moving masses (vegetation), abscess, new MR, prosthetic valve dehiscence | 2. Fever > 38°C |
| 3. Embolic phenomenon | |
| 4. Immunological disease (GN, Osler's nodes, Roth spots, RF) | |
| 5. Atypical organisms in blood culture | |
| 6. Other echo features of endocarditis |
High Yield — Modified Duke Criteria for IE Diagnosis
This is directly examinable. Know the 2 major criteria and 6 minor criteria cold. The key discriminators: typical organisms for the first major criterion means Strep. viridans, Strep. bovis, HACEK, Staph. aureus (community-acquired without a primary focus), or persistently positive cultures with any organism. An atypical organism in a single set is only a minor criterion.
Streptococcus viridans (e.g., sanguis, mutans) — oropharynx, penicillin-sensitive, > 50% of IE. Strep. bovis — GI, penicillin-sensitive, elderly, underlying colon CA or polyp (MUST screen!). Strep. group A — penicillin-sensitive, beta-haemolytic, attacks normal valves. Strep. group B — penicillin-sensitive, friable vegetations. Enterococci (faecalis, faecium) — GI/urethra, relatively penicillin-resistant, need aminoglycoside (cephalosporin-resistant), post-GI/GU manipulation. Staphylococci (aureus, epidermidis) — skin, variable sensitivity, fulminant valve destruction, prosthetic valve, IV drug addicts. HACEK — oropharynx, variable sensitivity, large vegetations, difficult to isolate. [1]
| Organism | Source | Key Association | Antibiotic |
|---|---|---|---|
| Strep. viridans | Oropharynx | Commonest overall ( > 50% IE) | Penicillin |
| Strep. bovis | GI tract | Colon cancer / polyps (MUST colonoscopy!) | Penicillin |
| Enterococcus | GI/GU tract | Post-GI/GU procedure | Penicillin + aminoglycoside (cephalosporin-resistant!) |
| Staph. aureus | Skin | IV drug users, prosthetic valves, acute fulminant IE | Flucloxacillin; vancomycin if MRSA |
| Staph. epidermidis | Skin | Prosthetic valve (early PVE) | Vancomycin + rifampicin + gentamicin |
| HACEK | Oropharynx | Large vegetations, culture-negative (slow-growing) | Ceftriaxone |
Strep. bovis IE = Colonoscopy
Any patient diagnosed with Strep. bovis endocarditis MUST be investigated for underlying colonic pathology (cancer, polyps). This is a favourite exam question.
Various classifications: bio-assay (beta-haemolysis), serology (Lancefield groups). Group A Strep. pyogenes — rheumatic fever, SBE, scarlet fever, toxic shock, pharyngitis, cellulitis, GN. Group B — S. agalactiae — neonatal sepsis, UTI, SBE. [1]
Causes: (1) Inadequate technique; (2) Prior antibiotics; (3) Fastidious organisms — Mycoplasma, HACEK (Haemophilus, Actinobacillus, Cardiobacterium/Capnocytophaga, Eikenella, Kingella), Abiotrophia, Bartonella; (4) Fungal (IV drug addicts). [1]
Why this matters: Up to 10–15% of IE cases are culture-negative. Prior antibiotics is the most common cause. HACEK organisms are notorious because they grow slowly and may require prolonged incubation ( > 5 days). Always inform the microbiology lab of suspected IE so they can extend incubation and use special media.
Initiate treatment according to likely organisms while pending cultures. Principles: (1) Eradicate source of infection (e.g., dental extraction); (2) Bactericidal agents — because host defence is reduced (no blood supply inside vegetations); (3) IV and high-dose antibiotics; (4) Adequate duration; (5) Surgery and complications management. [1]
Clinical assessment of progress: (1) Physical signs, body weight; (2) Urine testing; (3) Renal function, blood counts, ESR (may take weeks to decrease), drug levels; (4) Echocardiogram; (5) Fever may take 1–2 weeks to decrease. [1]
Why bactericidal, not bacteriostatic? Within vegetations, bacteria are embedded in a fibrin–platelet matrix that shields them from phagocytes and complement. The immune system cannot help clear infection there. Only bactericidal drugs (penicillins, aminoglycosides, vancomycin) can sterilise these protected niches. Bacteriostatic drugs (tetracyclines, macrolides) merely halt growth, which is insufficient.
Streptococcus (MIC < 0.1 μg/mL): Penicillin G 12–18 megaunits + Gentamicin 1 mg/kg Q8h for 2 weeks. Penicillin-resistant or allergic: Vancomycin 15 mg/kg Q12h for 4–6 weeks. MRSA: Vancomycin. [1]
| Scenario | Regimen | Duration |
|---|---|---|
| Strep. viridans (penicillin-sensitive) | IV Pen G + Gentamicin | 2 weeks (synergistic short course) |
| Penicillin-resistant / pen-allergic | IV Vancomycin | 4–6 weeks |
| MRSA | IV Vancomycin | 4–6 weeks |
| Enterococcus | IV Ampicillin + Gentamicin | 4–6 weeks |
| Prosthetic valve (Staph.) | Vancomycin + Rifampicin + Gentamicin | 6+ weeks |
1. Native valve endocarditis: haemodynamic instability (e.g., HF), large/recurrent emboli; 2. Prosthetic valve endocarditis: early (< 3 months) — usually intra-operative contamination, usually Staphylococcus; late ( > 3 months) — because of foreign bodies, early surgery often required; 3. Fungal endocarditis. [1]
High Yield — Surgical Indications in IE
Think of three main categories for surgery: (1) Heart failure from acute valvular destruction/regurgitation, (2) Uncontrolled infection (persistent fever > 7–10 days on appropriate antibiotics, abscess, fungal IE), (3) Prevention of embolism (large > 10 mm mobile vegetation, especially after embolic event). Prosthetic valve IE and fungal IE almost always need surgery.
Clinical presentation is variable — acute to low-grade fever. Broad spectrum of complications — cardiac and neurologic. Diagnosis should be suspected in patients with fever in the setting of relevant cardiac and non-cardiac risk. 3 sets of blood culture. Echocardiography. [1]
Antibiotic Prophylaxis for IE — New Guidelines
An abnormal valve with turbulence → bacterial adherence → infection. A normal valve → no bacterial adherence → no infection. Antibiotic prophylaxis aims to kill bacteria during the transient bacteraemia caused by a procedure, covering the period when bacteria are in the blood. [1]
The lecture shows a pharmacokinetic graph [1]: 2 g oral amoxicillin taken 30–60 minutes before a dental procedure produces serum levels above the MIC for streptococci during the entire period of transient bacteraemia.
Primary reasons: (1) IE is much more likely to result from frequent random bacteraemia from daily activities (brushing teeth, chewing) than from procedure-related bacteraemia; (2) Prophylaxis may prevent an exceedingly small number of IE cases; (3) Risk of antibiotic-associated adverse events exceeds the benefit; (4) Maintaining optimal oral health/hygiene is more important than prophylactic antibiotics. [1]
Cardiac conditions with the highest risk of adverse outcome from IE for which prophylaxis with dental procedures is reasonable: (1) Prosthetic cardiac valve or prosthetic material used for valve repair; (2) Previous IE; (3) Congenital heart disease — unrepaired cyanotic CHD (including palliative shunts/conduits), completely repaired CHD with prosthetic material (first 6 months after procedure), repaired CHD with residual defects adjacent to prosthetic patch/device; (4) Cardiac transplant recipients who develop cardiac valvulopathy. [1]
High Yield — IE Prophylaxis Indications
Only 4 categories of patients need prophylaxis. The most common exam trap is offering prophylaxis to patients with simple valve disease (e.g., mitral valve prolapse, bicuspid aortic valve). These do NOT qualify under current guidelines. Only prosthetic valves, prior IE, specific CHD, and transplant valvulopathy qualify.
Only dental procedures involving manipulation of gingival tissues, periapical region of teeth, or perforation of oral mucosa. Also procedures on respiratory tract or infected skin/musculoskeletal tissue. Prophylaxis solely to prevent IE is NOT recommended for GU or GI tract procedures. [1]
| Procedure | Prophylaxis? |
|---|---|
| Dental extraction | Yes (if high-risk cardiac condition) |
| Dental cleaning/scaling | Yes |
| Colonoscopy / upper endoscopy | No |
| Cystoscopy / urological procedure | No |
| Bronchoscopy with biopsy | Yes |
| Incision & drainage of infected skin | Yes |
Standard prophylaxis regimen: Amoxicillin 2 g PO single dose, 30–60 minutes before procedure. If penicillin-allergic: clindamycin 600 mg PO, or azithromycin/clarithromycin 500 mg PO.
Integration with Related Material
The tutorial uses a 50-year-old man with MVP, 2-week fever, displaced apex, pansystolic murmur at apex, painful red raised lesion on palm (Osler's node), Roth spots on fundoscopy, RBC 2+ in urine, Hb 10.5, WCC 15. This is a textbook IE presentation and directly mirrors the lecture content. Learning objectives include: DDx of reduced exercise capacity/SOB, pathophysiology of HF, presentation + Duke criteria + common pathogens of IE, complications, and treatment [2].
- 2023 Fourth Summative Minicase (Case 3): Blood culture growing Staph. aureus, persistent fever, lower limb weakness → infective spondylitis as a complication of bacteraemia/IE. Asks about neurological examination, organisms causing infective spondylitis, and management principles [5].
- 2024 Fourth Summative SAQ Q7: Septic arthritis in a child — overlaps with the concept of bacteraemia from a distant source (otitis media) seeding to joints/bone, which shares the same pathogenic mechanism as IE (bacteraemia → seeding of vulnerable site) [6].
- Various MCQs test Modified Duke criteria, IE prophylaxis indications, and valve lesion auscultatory findings.
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"A 35-year-old woman from rural China presents with palpitations, confused speech, and an irregular pulse at 110 bpm. Examination reveals parasternal heave, loud S1, mid-diastolic murmur at apex, and pansystolic murmur radiating to axilla. What are the diagnoses?"
- MS with AF + MR (rheumatic heart disease). The confused speech could be embolic stroke from LA thrombus [7].
- Mark scheme points: identify MS (mid-diastolic rumble, loud S1), MR (pansystolic → axilla), AF (irregular pulse), likely rheumatic aetiology, embolic stroke as complication.
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"List the Modified Duke criteria for definite IE."
- 2 major OR 1 major + 3 minor OR 5 minor.
- Major: (1) persistent bacteraemia with typical organisms; (2) endocardial involvement on echo.
- Minor: predisposing lesion/IVDU, fever > 38°C, embolic phenomenon, immunological disease, atypical organisms, other echo features.
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"A patient with Strep. bovis IE. What additional investigation must you order and why?"
- Colonoscopy — strong association with colonic carcinoma/polyps.
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"Name 4 indications for IE prophylaxis."
- Prosthetic valve, prior IE, specific CHD (unrepaired cyanotic, repaired with prosthetic material < 6 months, repaired with residual defect), cardiac transplant with valvulopathy.
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"Compare Osler's nodes and Janeway lesions."
- Osler's: painful, finger pulps, immune complex. Janeway: painless, palms/soles, septic emboli.
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"What is the antibiotic treatment for penicillin-sensitive Strep. viridans IE?"
- IV Penicillin G 12–18 megaunits + IV Gentamicin 1 mg/kg Q8h for 2 weeks.
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"A 75-year-old woman with syncope on exertion and an ejection systolic murmur radiating to the neck. Pulse is slow-rising. What is the most likely diagnosis, and why is this dangerous?"
- Severe AS; symptomatic AS has 50% mortality in 3 years without intervention; syncope carries ~3-year survival.
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"Name three causes of culture-negative endocarditis."
- Prior antibiotics, fastidious organisms (HACEK, Bartonella), fungal infection, inadequate technique.
Active Recall - Fever and a Murmur
High Yield Summary
Valvular heart disease: Stenosis → pressure overload → hypertrophy; Regurgitation → volume overload → dilatation. MS is 95% rheumatic with mid-diastolic rumble, loud S1, OS, and frequently complicated by AF and embolism. AS presents with the triad of angina, syncope, and HF — symptomatic AS = 50% mortality in 3 years without AVR. AR has wide pulse pressure and multiple eponymous signs. MR causes a pansystolic murmur to axilla. TR has a pansystolic murmur at LSB increased by inspiration.
Infective endocarditis: Suspect in any patient with fever + known cardiac risk factors. Diagnose with Modified Duke criteria (2 major / 1 major + 3 minor / 5 minor). 3 sets of blood cultures + TTE/TOE. Commonest organism overall is Strep. viridans ( > 50%); Staph. aureus in IVDU and prosthetic valves. Strep. bovis → colonoscopy. Treatment is IV, high-dose, bactericidal antibiotics for 2–6 weeks. Surgery for HF, uncontrolled infection, large vegetation/recurrent emboli, PVE, and fungal IE.
IE prophylaxis: Only 4 high-risk cardiac conditions qualify. Only dental/oral mucosal procedures and procedures on infected tissue. NOT for GI/GU procedures. Standard: amoxicillin 2 g PO 30–60 min before. Optimal oral hygiene > prophylactic antibiotics.
[1] Lecture slides: GC 050. Fever and a murmur.pdf (all pages) [2] Lecture slides: GC_Interactive tutorial (Cardiac case 1) student copy.pdf (pp.1, 3) [3] Senior notes: Maksim Medicine Notes.pdf (p.38 — Rheumatic heart disease) [4] Senior notes: Block A - Fever and a murmur_ Valvular heart diseases; Infective endocarditis.pdf (p.7 — AF mechanism in MS) [5] Past papers: 2023 Fourth Summative Minicase.pdf (pp.21, 25 — Case 3, Staph. aureus bacteraemia/infective spondylitis) [6] Past papers: 2024 Fourth Summative SAQ.pdf (p.8 — Q7, septic arthritis) [7] Senior notes: MBBS Final MB (Surgery) (Felix PY Lai).pdf (p.1167 — Case 2, MS with AF and stroke)
GC049 Fever After A Blood Transfusion
A febrile reaction occurring during or shortly after a blood transfusion, most commonly caused by recipient antibodies against donor leukocyte antigens or cytokines accumulated in stored blood products.
GC051 Fever And Confusion: Meningitis And Encephalitis; Suppurative Brain Infection
Fever accompanied by altered mental status can indicate meningitis (infection/inflammation of the meninges), encephalitis (infection/inflammation of the brain parenchyma), or suppurative brain infections such as cerebral abscess, which are life-threatening conditions requiring urgent diagnosis and treatment.