• Sudden, severe breathlessness, often worse on lying flat (orthopnea) and may wake the patient from sleep.
• Tachypnea with increased work of breathing and inability to speak full sentences.
• Cough, classically with pink, frothy, blood-tinged sputum.
• Marked anxiety, restlessness, and a feeling of suffocation.
• Sweating, pallor, and cold clammy skin.
• Cyanosis and low oxygen saturation in severe cases.
• Tachycardia; blood pressure may be high initially, while hypotension can indicate severe cardiac failure or shock.
• Chest examination: widespread fine inspiratory crackles (crepitations), usually beginning at the lung bases and spreading upward. Wheeze may occur, termed cardiac asthma.
• In cardiogenic edema, there may also be signs of left-sided heart failure: raised JVP, S3 gallop, peripheral edema, or an underlying cardiac murmur.

Clinical features of infective endocarditis

Constitutional features

• Fever is the most common feature, though it may be absent in older adults or subacute disease.
• Chills, night sweats, malaise, fatigue, anorexia, and weight loss.
• Myalgia and arthralgia may occur.

Cardiac features

• A new regurgitant murmur or change in a pre-existing murmur.
• Tachycardia.
• Features of heart failure due to valvular destruction, such as dyspnea, orthopnea, pulmonary edema, and peripheral edema.
• Conduction defects may suggest a peri-valvular abscess.

Peripheral stigmata

• Petechiae on skin, conjunctivae, or oral mucosa.
• Splinter hemorrhages beneath the nails.
• Osler nodes: painful, tender nodules on finger or toe pads.
• Janeway lesions: painless erythematous or hemorrhagic macules on palms and soles.
• Roth spots: retinal hemorrhages with pale centers.
• Clubbing may occur in prolonged subacute disease.

Embolic and vascular manifestations

• Systemic emboli can cause stroke, acute limb ischemia, renal infarction, splenic infarction, or mesenteric ischemia.
• Right-sided endocarditis, especially in people who inject drugs, may cause septic pulmonary emboli with pleuritic chest pain, cough, hemoptysis, and pulmonary infiltrates.
• Mycotic aneurysm or intracranial hemorrhage can occur.

Immunologic and reticuloendothelial features

• Splenomegaly, particularly in subacute infective endocarditis.
• Glomerulonephritis causing hematuria, proteinuria, and renal impairment.
• Positive rheumatoid factor may be present.

NYHA Functional Classification

• Class I: symptoms with no activity
• Class II: symptoms with ordinary activity
• Class III: symptoms with less-than-ordinary activity
• Class IV: symptoms at rest

Mechanism in Marfan syndrome

• Defective connective tissue, usually due to an FBN1 mutation, causes skeletal features such as scoliosis, tall stature, arachnodactyly, pectus deformity, and joint laxity.
• The same connective-tissue weakness affects the aortic wall, causing aortic-root dilatation.
• Dilatation stretches the aortic valve annulus and prevents the valve cusps from meeting properly in diastole.
• This produces aortic regurgitation. Aortic-root dilatation also raises the risk of aortic aneurysm and dissection.

Grading of chronic aortic regurgitation

Key points

• Vena contracta >6 mm, regurgitant volume ≥60 mL, regurgitant fraction ≥50%, and holodiastolic flow reversal in the descending aorta strongly support severe AR.
• A chronic severe AR usually produces left-ventricular dilatation due to persistent volume overload.
• In acute severe AR, the left ventricle may not yet be dilated, so do not exclude severity on the basis of a normal LV size.
• Pressure half-time is influenced by left-ventricular compliance and blood pressure, so it is supportive rather than definitive when used alone.

Investigations in aortic regurgitation

1. Transthoracic echocardiography with Doppler - first-line test

• Valve morphology and cause: bicuspid valve, rheumatic disease, infective endocarditis, or aortic-root dilatation.
• Severity of regurgitation using colour and spectral Doppler.
• Left-ventricular size, volumes, systolic function, and ejection fraction.
• Aortic-root and ascending-aorta dimensions.
• Associated valve lesions and pulmonary pressures.

2. ECG

• Left ventricular hypertrophy, often with strain pattern.
• Left-axis deviation or conduction abnormalities.
• Arrhythmias, especially in advanced LV dilatation.

3. Chest radiograph

• Cardiomegaly due to left-ventricular enlargement.
• Dilated aortic root or ascending aorta.
• Pulmonary venous congestion or pulmonary edema if heart failure develops.

4. Cardiac magnetic resonance imaging

• Regurgitant volume and regurgitant fraction.
• LV volumes and ejection fraction.
• Aortic-root and thoracic-aortic dimensions.
• Myocardial fibrosis and ventricular remodeling.

5. CT angiography of the aorta

• Aortic aneurysm
• Aortic dissection
• Marfan syndrome or another connective-tissue aortopathy
• Preoperative need for detailed aortic anatomy

6. Exercise testing or stress echocardiography

7. Laboratory investigations - directed by suspected cause

• Blood cultures: if infective endocarditis is suspected.
• CBC, ESR/CRP: support evaluation for infection or inflammation.
• Renal function and electrolytes: baseline assessment, especially if heart failure or surgery is likely.
• Troponin: if acute chest pain or acute coronary syndrome is suspected.
• Syphilis serology or autoimmune tests only when the history or examination suggests these causes.

8. Cardiac catheterization and coronary angiography

• Noninvasive imaging is inconclusive.
• Coronary artery disease is suspected before valve surgery.
• Hemodynamic measurements are required in selected cases.

Treatment of aortic regurgitation

1. Acute severe aortic regurgitation - emergency

• Admit to a monitored/critical-care setting and obtain urgent echocardiography.
• Give oxygen and treat pulmonary edema if present.
• IV vasodilator, such as nitroprusside, may reduce afterload and improve forward cardiac output if blood pressure permits.
• An inotrope such as dobutamine may be needed in hypotension or low-output states.
• Treat the cause, for example IV antibiotics for infective endocarditis.
• Urgent aortic valve surgery, often with aortic-root surgery if dissection is present, is usually required.

2. Chronic aortic regurgitation

Mild or moderate AR

• Clinical and echocardiographic surveillance.
• Treat associated hypertension, preferably with an afterload-reducing drug such as an ACE inhibitor, ARB, or dihydropyridine calcium-channel blocker.
• Treat the underlying condition, such as aortic-root disease, rheumatic disease, or infective endocarditis.
• Monitor aortic-root size in bicuspid valve disease, Marfan syndrome, and other aortopathies.

Severe chronic AR

• Surgical aortic valve replacement (SAVR) is the usual treatment.
• Aortic valve repair may be possible in selected patients at specialist centers.
• If the aortic root/ascending aorta is dilated, combined valve and aortic-root replacement or valve-sparing root surgery may be needed.

Indications for surgery in severe chronic AR

1. Symptoms attributable to severe AR, such as exertional dyspnea, angina, reduced exercise tolerance, or heart failure.
2. LV systolic dysfunction, even if asymptomatic. ACC/AHA guidance uses LVEF ≤55% as an important threshold.
3. Marked progressive LV dilatation, particularly:
   • LV end-systolic diameter >50 mm, or
   • indexed LV end-systolic diameter >25 mm/m².
4. Severe AR when another cardiac operation, such as CABG or surgery on the ascending aorta, is already planned.
5. Acute severe AR due to endocarditis or aortic dissection.

Role of medical treatment

Transcatheter valve replacement

Signs of Marfan syndrome

1. Skeletal signs

• Tall, thin build with disproportionately long limbs: dolichostenomelia
• Increased arm-span-to-height ratio
• Long, slender fingers: arachnodactyly
• Positive thumb sign (Steinberg sign): thumb protrudes beyond the ulnar border when enclosed in a clenched fist.
• Positive wrist sign (Walker-Murdoch sign): thumb and little finger overlap when encircling the opposite wrist.
• Pectus carinatum or pectus excavatum
• Scoliosis or kyphosis
• Pes planus, hindfoot deformity
• Joint hypermobility, though contractures can occur in some individuals
• Reduced elbow extension
• High-arched palate and dental crowding
• Protrusio acetabuli

2. Ocular signs

• Ectopia lentis, usually upward and outward lens subluxation
• Myopia
• Flattened cornea
• Increased risk of retinal detachment, early cataract, and glaucoma

3. Cardiovascular signs

• Aortic-root dilatation, especially at the sinuses of Valsalva
• Aortic aneurysm or dissection
• Aortic regurgitation due to aortic-root dilatation
• Mitral valve prolapse, sometimes with mitral regurgitation

4. Other features

• Spontaneous pneumothorax
• Dural ectasia, which may cause low-back pain, headache, or neurologic symptoms
• Striae atrophicae not explained by marked weight change or pregnancy
• Recurrent hernia
• Characteristic facial appearance may include a long narrow face, deep-set eyes, and retrognathia.