What are the clinical presentations, management, and treatment options for aortic stenosis, aortic regurgitation, mitral stenosis, and mitral regurgitation, according to Harrison's Principles of Internal Medicine (Harrison's Principles of Internal Medicine) 21st edition?

Valvular Heart Disease: Clinical Summary and Quiz

AORTIC STENOSIS

Clinical Presentation

Aortic stenosis presents with the classic triad of exertional dyspnea, angina, and syncope—once any symptom develops, average survival without intervention is 2-3 years. 1

• Severe AS is defined by: peak velocity ≥4 m/sec, mean gradient ≥40 mmHg, and aortic valve area ≤1.0 cm² 1
• Exercise stress testing should be performed in asymptomatic patients to unmask occult symptoms and measure BNP levels to detect subclinical decompensation 2
• In low-flow low-gradient AS, dobutamine stress echocardiography distinguishes true-severe from pseudo-severe stenosis 2

Management Strategy

There is no medical therapy that modifies the natural history of aortic stenosis—aortic valve replacement (surgical or transcatheter) is the only definitive treatment. 2

• Symptomatic patients with severe AS require immediate valve replacement (surgical AVR or TAVI), as this is a Class I indication regardless of left ventricular function 1
• Asymptomatic patients with severe AS should undergo intervention if: LVEF falls to ≤50%, symptoms develop on exercise testing, or very severe AS (peak velocity >5 m/sec) is present 1
• For hypertension management in AS patients, ACE inhibitors or ARBs are first-line agents as they reduce LV fibrosis and dyspnea 2
• Beta-blockers should be avoided in AS unless there is a compelling indication (heart failure with reduced EF, post-MI, or significant arrhythmias) 2

Perioperative Considerations

• In patients with severe AS requiring urgent non-cardiac surgery, the procedure should be performed under careful hemodynamic monitoring with meticulous heart rate control and fluid management 1
• For elective non-cardiac surgery in symptomatic AS patients, valve replacement should be performed first; in high-risk patients, TAVI is the preferred option 1

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AORTIC REGURGITATION

Clinical Presentation: Acute vs. Chronic

Aortic regurgitation presents dramatically differently depending on acuity—acute AR causes severe pulmonary edema and cardiogenic shock requiring emergency surgery, while chronic AR progresses insidiously over years with compensatory LV remodeling. 3

• Acute severe AR: Sudden volume overload on a non-compliant LV causes rapid pulmonary edema, hypotension, and cardiovascular collapse 3
• Chronic AR: Exertional dyspnea is typically the first symptom, followed by fatigue, palpitations, and orthopnea as compensatory mechanisms fail 3
• Once symptoms develop in chronic AR, annual mortality rises to 10-25%, making symptom onset an absolute indication for surgery 4, 3

Management of Acute Severe AR

Medical therapy serves only as a temporizing bridge to emergency surgery and should never delay surgical intervention. 4

• Vasodilators (sodium nitroprusside or IV nitroglycerin) should be administered immediately to reduce LV afterload and improve forward flow 4
• Beta-blockers are absolutely contraindicated in acute AR as they prolong diastole and increase regurgitant volume 4
• Emergency surgical valve replacement is mandatory—delay increases mortality exponentially 4

Management of Chronic Symptomatic AR

Surgery is indicated for all symptomatic patients with severe AR regardless of left ventricular function, as mortality reaches 10-25% once symptoms occur. 4

• ACE inhibitors or dihydropyridine calcium channel blockers (nifedipine 30-90 mg daily) should be used for blood pressure control and afterload reduction 4
• Target systolic blood pressure <140 mmHg to reduce LV wall stress 4
• Never delay surgery in symptomatic patients to "optimize" medical therapy—symptoms indicate decompensation and immediate intervention is required 4, 3

Management of Asymptomatic Severe AR

Surgery is indicated when LVEF falls to ≤50-55% or LV end-systolic diameter reaches ≥50 mm (or 25 mm/m²) in asymptomatic patients. 4

• Vasodilators (nifedipine or ACE inhibitors) may prolong the compensated phase and delay need for surgery in asymptomatic patients with normal LV function 4
• Echocardiography should be performed every 6-12 months to monitor for LV dysfunction or progressive dilatation 4
• More frequent monitoring (every 3-6 months) is warranted if LVEF begins declining or end-systolic dimensions increase 4

Critical Pitfalls

• Do not use beta-blockers for rate control or blood pressure management in AR, as they worsen hemodynamics by prolonging diastole 4
• Avoid aggressive diuresis in patients with small LV chambers, as preload reduction can compromise cardiac output 4

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MITRAL STENOSIS

Clinical Presentation

Mitral stenosis with valve area <1.5 cm² is usually poorly tolerated, particularly during pregnancy, and causes progressive dyspnea, orthopnea, and pulmonary hypertension. 1

• Symptoms are exacerbated by conditions that increase heart rate or cardiac output (exercise, pregnancy, atrial fibrillation) 1
• Systolic pulmonary artery pressure >50 mmHg indicates severe hemodynamic compromise 1

Management Strategy

• Percutaneous mitral commissurotomy (PMC) is the preferred intervention for symptomatic patients with suitable valve anatomy (pliable leaflets, minimal calcification, no significant MR) 1
• In symptomatic patients or those with pulmonary artery pressure >50 mmHg requiring high-risk non-cardiac surgery, PMC should be attempted before the procedure 1
• Surgical valve replacement or repair is indicated when valve anatomy is unsuitable for PMC or when severe MR coexists 1
• Heart rate control is critical perioperatively, particularly in patients with atrial fibrillation, to allow adequate diastolic filling time 1

Special Considerations

• Moderate or severe MS (valve area <1.5 cm²) in pregnant women is poorly tolerated; PMC should be considered in severely symptomatic patients (NYHA class III-IV) 1
• Non-cardiac surgery can be performed safely in patients with non-significant MS (valve area >1.5 cm²) and in asymptomatic patients with systolic PA pressure <50 mmHg 1

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MITRAL REGURGITATION

Classification: Primary vs. Secondary

Mitral regurgitation must be classified as primary (valvular pathology such as leaflet prolapse) or secondary (ventricular remodeling causing leaflet malcoaptation), as management differs fundamentally between these etiologies. 1

Management of Primary MR

Surgery is indicated in symptomatic patients with severe primary MR, or in asymptomatic patients with LVEF ≤60% or LV end-systolic diameter ≥40 mm. 1

• Mitral valve repair is strongly preferred over replacement when feasible, as it preserves LV function and avoids prosthetic valve complications 1
• Surgery should be considered in patients with moderate primary MR undergoing left-sided valve surgery 1
• Percutaneous mitral repair (MitraClip) may be the preferred treatment in specific subsets of severe primary MR within strict selection criteria 1

Management of Secondary MR

Secondary MR management focuses on treating the underlying LV dysfunction with guideline-directed medical therapy for heart failure, with intervention reserved for persistent severe MR despite optimal medical therapy. 1

• The optimal timing of intervention in secondary MR is controversial, as the regurgitation is a consequence rather than the cause of LV dysfunction 1
• Intervention should be based on symptoms and objective consequences rather than severity indices alone 1

Perioperative Considerations

• Non-cardiac surgery can be performed safely in asymptomatic patients with severe MR and preserved LV function 1
• If LV dysfunction is severe (EF <30%), non-cardiac surgery should be performed only if strictly necessary, after optimization of heart failure medical therapy 1

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COMBINED AND MULTIPLE VALVE DISEASE

General Principles

When managing combined valve disease, assess each lesion individually but also consider hemodynamic interactions—for example, coexistent MR may underestimate AS severity by reducing transvalvular flow and gradients. 1, 5

• When either stenosis or regurgitation is predominant, management follows recommendations for the predominant lesion 1
• When severity is balanced, base intervention decisions on symptoms and objective consequences (LV dysfunction, dilatation) rather than severity indices alone 1
• Pressure gradients reflecting hemodynamic burden become more important than valve area or regurgitation measures in combined disease 1
• Intervention can be considered for non-severe multiple lesions if they collectively cause symptoms or LV impairment 1

AS with Concurrent MR

Moderate or severe MR is present in up to one-third of patients with severe AS and is mainly functional; MR severity improves in just over half of patients following aortic valve replacement. 6, 7

• MR is more likely to improve after balloon-expandable compared to self-expandable transcatheter valves 6
• Simultaneous replacement of both valves is associated with significantly higher morbidity and mortality 7
• Current practice favors staged procedures: perform AVR first, then re-evaluate MR severity before considering mitral intervention 7

Combined AR and MR

Combined aortic and mitral regurgitation causes severe volume overload; LV dysfunction is frequent at presentation and even more common postoperatively, suggesting surgery should not be delayed when symptoms occur or subtle LV dysfunction develops. 8

• The decision to operate on one or both valves depends on severity of each lesion, age, comorbidities, increased operative risk of double valve surgery, and risk of leaving one valve unoperated 8
• Multidisciplinary heart valve team evaluation is critical to optimize management 8

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PROSTHETIC VALVES

Valve Selection

Rather than arbitrary age cutoffs, prosthesis choice should be individualized based on anticoagulation bleeding risk with mechanical valves versus structural deterioration risk with bioprostheses, considering patient lifestyle and preferences. 1

• Randomized trials show similar survival between mechanical and biological prostheses, with no significant difference in thromboembolism rates 1
• Mechanical valves have higher bleeding rates; bioprostheses have higher reintervention rates 1
• Bioprostheses should be considered when life expectancy is lower than the presumed durability of the prosthesis 1

Anticoagulation in Pregnancy

Pregnancy in women with mechanical valves, especially in the mitral position, carries high maternal and fetal complication risk; therapeutic anticoagulation is of utmost importance. 1

• In patients requiring <5 mg warfarin, continue oral anticoagulants throughout pregnancy and switch to UFH before delivery 1
• In patients requiring higher warfarin doses, switch to LMWH during first trimester with strict anti-Xa monitoring (therapeutic range 0.8-1.2 IU/mL), then resume oral anticoagulants 1
• Maternal mortality is estimated at 1-4% and serious events occur in up to 40% of women with mechanical valves 1

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QUIZ: Valvular Heart Disease

Question 1: A 68-year-old man with severe aortic stenosis (peak velocity 4.8 m/sec, mean gradient 52 mmHg, AVA 0.7 cm²) is asymptomatic but has hypertension. Which antihypertensive agent is preferred?

• A) Metoprolol
• B) Lisinopril
• C) Diltiazem
• D) Hydralazine

Question 2: A 45-year-old woman presents with acute severe aortic regurgitation from endocarditis, causing pulmonary edema and hypotension. What is the immediate management priority?

• A) Start metoprolol to reduce heart rate
• B) Administer IV nitroprusside and arrange emergency surgery
• C) Optimize with diuretics and ACE inhibitors for 2 weeks before surgery
• D) Perform urgent echocardiography to confirm diagnosis before any intervention

Question 3: An asymptomatic 52-year-old man with chronic severe aortic regurgitation has LVEF 48% and LV end-systolic diameter 52 mm. What is the appropriate management?

• A) Continue observation with echocardiography every 6 months
• B) Start nifedipine and reassess in 3 months
• C) Proceed with surgical aortic valve replacement
• D) Initiate beta-blocker therapy

Question 4: A 35-year-old pregnant woman at 20 weeks gestation with severe mitral stenosis (valve area 0.9 cm²) develops NYHA class III symptoms despite medical therapy. What is the preferred intervention?

• A) Immediate surgical mitral valve replacement
• B) Percutaneous mitral commissurotomy
• C) Increase diuretic dose and continue to term
• D) Emergency cesarean section followed by valve surgery

Question 5: A 72-year-old man undergoes TAVR for severe aortic stenosis. He has moderate functional mitral regurgitation. What is the recommended approach to the MR?

• A) Simultaneous transcatheter mitral valve repair
• B) Perform TAVR first, then reassess MR severity afterward
• C) Convert to open surgery for double valve replacement
• D) Treat MR medically and defer TAVR

Question 6: Which statement about beta-blockers in valvular heart disease is correct?

• A) They are first-line therapy for hypertension in aortic stenosis
• B) They are contraindicated in acute aortic regurgitation
• C) They improve outcomes in chronic mitral regurgitation
• D) They are essential for rate control in mitral stenosis with atrial fibrillation

Question 7: A 58-year-old woman with severe symptomatic primary mitral regurgitation has LVEF 55% and LV end-systolic diameter 38 mm. What is the indication for surgery?

• A) Symptoms alone are sufficient indication
• B) Wait until LVEF falls below 50%
• C) Wait until LV end-systolic diameter reaches 40 mm
• D) Surgery is not indicated as LV function is preserved

Question 8: In combined aortic stenosis and mitral regurgitation, why might AS severity be underestimated?

• A) MR increases afterload on the aortic valve
• B) MR decreases stroke volume across the aortic valve, lowering gradients
• C) MR causes LV hypertrophy that masks AS
• D) Echocardiography cannot accurately measure gradients in combined disease

Question 9: What is the target systolic blood pressure in a patient with chronic symptomatic aortic regurgitation?

• A) <120 mmHg
• B) <140 mmHg
• C) <160 mmHg
• D) No specific target; avoid all antihypertensives

Question 10: A 42-year-old woman with a mechanical mitral valve is planning pregnancy. She requires 7 mg warfarin daily. What is the recommended anticoagulation strategy?

• A) Continue warfarin throughout pregnancy
• B) Switch to LMWH during first trimester with anti-Xa monitoring, then resume warfarin
• C) Switch to UFH throughout pregnancy
• D) Switch to aspirin and clopidogrel during pregnancy

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Answer Key:

1. B - ACE inhibitors (lisinopril) are first-line for hypertension in AS; beta-blockers should be avoided
2. B - Immediate vasodilators and emergency surgery; beta-blockers are contraindicated
3. C - Surgery indicated when LVEF ≤50-55% or LVESD ≥50 mm in asymptomatic severe AR
4. B - PMC is preferred for symptomatic severe MS in pregnancy
5. B - Staged approach: TAVR first, reassess MR afterward
6. B - Beta-blockers are contraindicated in acute AR (prolong diastole, increase regurgitant volume)
7. A - Symptoms alone are sufficient indication for surgery in severe primary MR
8. B - MR reduces transvalvular flow, lowering AS gradients and potentially underestimating severity
9. B - Target SBP <140 mmHg to reduce LV wall stress
10. B - LMWH during first trimester with anti-Xa monitoring (0.8-1.2 IU/mL), then warfarin