Diseases of the aortic valve: aortic stenosis

01Definition and overview

Aortic stenosis is narrowing of the aortic valve orifice that obstructs the ejection of blood from the left ventricle into the aorta. The normal valve area is 3 to 4 square centimetres, and the obstruction matters once it falls below about a third of that. Obstruction can also lie above the valve (supravalvular stenosis, as in Williams syndrome) or below it (a subaortic membrane, or the septal hypertrophy of hypertrophic cardiomyopathy); this topic is about the valve.

Severity is graded by echocardiography:

The gradient depends on the flow. When the ventricle is weak, or small and stiff, severe stenosis can produce only a low gradient. This low-flow, low-gradient stenosis (a stroke volume index of 35 mL per square metre or less) needs extra tests to confirm it.

02Etiology and pathophysiology

Causes

• Calcific aortic valve disease is the commonest cause, mostly after the age of 65. It begins much like atherosclerosis, with endothelial damage, lipid and lipoprotein deposition and inflammation (macrophages and T cells), and then becomes an active process of fibrosis and bone-like calcification of the cusps. Its risk factors are age, male sex, raised LDL cholesterol and lipoprotein(a), hypertension, diabetes, smoking and chronic kidney disease. Aortic sclerosis, thickening without obstruction, is its early stage.
• A bicuspid aortic valve is the commonest congenital heart abnormality, in 1 to 2 per cent of births, and sometimes familial. It calcifies and narrows one or two decades earlier, so it is the usual cause of stenosis under the age of 65. It goes with dilatation of the aortic root and ascending aorta, coarctation and a risk of dissection.
• Rheumatic disease fuses the commissures, nearly always with mitral disease, and is the main cause in low-income countries.
• Rare causes: radiation, Paget disease of bone, end-stage kidney disease, systemic lupus, and alkaptonuria.

In older patients, transthyretin cardiac amyloidosis often accompanies calcific stenosis. It thickens the ventricle, explains some low-flow states and worsens the prognosis.

What the obstruction does

1. 1

   Pressure overload

   To push blood through the narrow valve the ventricle generates a high systolic pressure, and responds with concentric hypertrophy, which keeps the wall stress and the ejection fraction normal for years.
2. 2

   A stiff ventricle

   The thick wall relaxes poorly, so filling depends on the atrial contraction, and the diastolic pressure rises. Atrial fibrillation is poorly tolerated.
3. 3

   Ischaemia

   The thick muscle needs more oxygen, while the high wall pressure and short diastole reduce flow to the subendocardium. Angina can occur with normal coronary arteries.
4. 4

   A fixed output

   On exercise the output cannot rise much across the valve, while the muscles' vessels dilate, so the blood pressure falls and the brain is underperfused: exertional syncope. Arrhythmias contribute.
5. 5

   Failure

   Eventually the muscle fibroses, the ejection fraction falls and the ventricle dilates, with pulmonary oedema and a low output.

Shear stress across the valve breaks down large von Willebrand multimers. Together with intestinal angiodysplasia this causes gastrointestinal bleeding (Heyde syndrome), which usually stops after valve replacement, though it can return.

03Clinical features

There are usually no symptoms until the valve is severely narrowed. Then come:

• exertional breathlessness and reduced exercise tolerance, often the first and most common symptom, and later orthopnoea and pulmonary oedema;
• angina on effort;
• exertional syncope or dizziness;
• fatigue, and in older patients a decline that is easily put down to age;
• rarely, sudden death, gastrointestinal bleeding or an embolism from the valve.

The signs:

• a slow-rising pulse of small volume (pulsus parvus et tardus), best felt at the carotid, and a narrow pulse pressure in severe disease; in older people stiff arteries can hide it;
• a sustained, undisplaced apex beat, sometimes with a palpable atrial impulse, and a systolic thrill in the aortic area;
• a harsh ejection systolic murmur, crescendo–decrescendo, loudest in the second right intercostal space and radiating to the carotids, sometimes heard best at the apex in the elderly (the Gallavardin phenomenon);
• a soft or absent aortic component of the second sound, and reversed splitting;
• an ejection click in a mobile bicuspid valve, and a fourth heart sound.

The later the murmur peaks in systole, and the softer the second sound, the more severe the stenosis. The loudness of the murmur is not a guide, because it falls when the output falls.

04Diagnosis and management

Tests

• ECG: left ventricular hypertrophy with a strain pattern (ST depression and T-wave inversion in I, aVL, V5 and V6), left atrial enlargement, and sometimes conduction disease, because calcium can spread into the conducting system.
• Chest X-ray: often a normal heart size with post-stenotic dilatation of the ascending aorta and a calcified valve on the lateral view; an enlarged heart when it fails.
• Echocardiography is the key test: the cusps and their calcification, the number of cusps, the peak velocity, the mean gradient, the valve area by the continuity equation, the wall thickness and the ejection fraction, and the aorta.
• When the ejection fraction is low and the gradient low, dobutamine stress echocardiography separates true severe stenosis (the gradient rises, the area stays small) from pseudo-severe stenosis (the area grows), and shows whether the ventricle has contractile reserve.
• A CT calcium score of the valve supports severe stenosis when it is high: severe stenosis is likely above about 2000 Agatston units in men and 1200 in women, and unlikely below 1600 and 800.
• An exercise test in apparently asymptomatic patients unmasks symptoms or a fall in blood pressure in about a third. It is never done in symptomatic patients.
• Natriuretic peptides help to time intervention. Before treatment, CT angiography plans a transcatheter valve, and the coronary arteries are imaged.

When to intervene

• All eligible patients with symptomatic severe stenosis are offered valve replacement, unless their life expectancy is under a year or their comorbidity means it would not improve their life.
• Symptoms brought out by an exercise test count as symptoms, and the patient is treated as symptomatic.
• Asymptomatic severe stenosis with an ejection fraction below 50 per cent that has no other cause, and severe stenosis in a patient who needs other heart surgery.
• A sustained fall in systolic pressure of more than 20 mmHg on exercise is a reason to consider intervention.
• In asymptomatic severe high-gradient stenosis, early intervention can be offered to patients at low procedural risk as an alternative to close surveillance, after a normal exercise test where feasible. It is favoured further by very severe stenosis (a velocity above 5 m/s or a mean gradient of 60 mmHg or more), heavy calcification with a velocity rising by 0.3 m/s a year or more, natriuretic peptides more than three times normal on repeated measurement, or an ejection fraction below 55 per cent. Trials of early surgery and early transcatheter replacement mainly reduced admissions to hospital, not deaths.
• In low-flow, low-gradient stenosis with a weak ventricle, intervention is advised once true severe stenosis is confirmed; with a preserved ejection fraction it is considered in symptomatic patients after careful confirmation.
• Moderate stenosis is replaced only during other heart surgery.

How to replace the valve

The Heart Team (cardiologists, surgeons and imaging specialists) weighs age and life expectancy, frailty and comorbidity, the anatomy and the access, the patient's preference and the lifetime plan, since a young patient may need several valves:

• Transcatheter aortic valve implantation (TAVI) places a bioprosthesis inside the diseased valve, usually through the femoral artery, under sedation. It is the recommended primary treatment for patients aged 70 or older with a tricuspid valve, suitable anatomy and femoral access, whatever their surgical risk, and for older or high-risk patients more generally. Its drawbacks are vascular complications, paravalvular leak and a need for a permanent pacemaker in some patients.
• Surgical aortic valve replacement is preferred under the age of 70 at low risk, in most bicuspid valves, in an aorta that needs surgery, and when the anatomy does not suit a catheter valve. A mechanical valve is usually chosen under 60, with lifelong warfarin, and a bioprosthesis over 65; between those ages the choice is shared with the patient.
• Balloon aortic valvuloplasty gives only short relief in adults and is kept as a bridge to definitive treatment in unstable patients. In children and adolescents with a non-calcified valve it can delay replacement for years.

Medical treatment

No drug slows the narrowing: statins, including simvastatin with ezetimibe, did not change it in trials, and they are given only for the usual cardiovascular reasons. Hypertension is treated, starting low and titrating slowly. Heart failure drugs relieve symptoms while the patient waits but must not delay intervention. Vasodilators, including nitrates, can drop the blood pressure dangerously in severe stenosis, and patients become fragile when dehydrated. Endocarditis prophylaxis is not routine for a native stenotic valve; it is given after valve replacement, surgical or transcatheter, and after previous endocarditis.

05Epidemiology

Aortic stenosis is the commonest valve disease leading to intervention in Europe and North America. Calcific disease is mainly one of old age: about 12 per cent of people over 75 have aortic stenosis, and about 3 per cent have severe stenosis. The number is rising as populations age. Bicuspid valves cause most stenosis in people under 65, more often in men. Rheumatic aortic stenosis, almost always with mitral disease, is seen mostly in low- and middle-income countries and in older migrants.

06Prognosis

Asymptomatic severe stenosis carries a low risk of sudden death, about 1 per cent a year, but most patients develop symptoms within a few years, and the velocity rises by about 0.2 to 0.3 m/s a year on average, faster in heavily calcified valves. The landmark description of the natural history found that, without valve replacement, the average survival was about 5 years after the onset of angina, 3 years after syncope and 2 years after heart failure. In older patients with symptomatic severe stenosis who could not have surgery, about half died within a year without valve replacement, even though most had a balloon valvuloplasty.

Valve replacement relieves symptoms and, in older patients, restores survival close to that of people of the same age; younger patients do less well than their peers. Outcomes are worse when the ejection fraction is low, the flow is low, there is pulmonary hypertension or the patient is frail. Bioprostheses, surgical or transcatheter, wear out over 10 to 20 years, and a failing bioprosthesis can often be treated by placing a transcatheter valve inside it. Patients need echocardiographic follow-up: every 6 months in asymptomatic severe stenosis, every year in moderate calcific disease, and every year after a tissue valve.