Aortic valve stenosisI35.0

In aortic valve stenosis, the heart valve becomes adhesions. The resulting restriction of mobility leads to a reduction of the valve opening area and thus to an obstruction of the forward blood flow (Herold 2018 / Anschütz 1974).

Depending on the location of the stenosis, the AS is divided into:

• in the case of a constriction at valve height, we speak of a valvular AS
• in case of a constriction below the aortic valve from a subvalvular AS
• in case of a narrowing above the aortic valve from supravalvular AS

Congenital stenoses of the aorta can occur in all 3 forms, acquired almost exclusively as valvular form (Gieretz 2010)

Aortic valve stenosis (AS) is the most common form of valve disease in Europe and North America (Herold 2018), accounting for 43% of all heart valve defects. The disease affects 80 % of the male sex (Bob 2001).

Patients between the ages of 16 and 65 years of age usually have a congenital bicuspid aortic valve, while older patients have a mostly tricuspid aortic valve with stenosis and calcification (Krakow 2005). Of the over 75-year-olds, about 4% are affected by AS (Pinger 2019).

Pathophysiologically, the following changes can be found in AS: the pressure load on the left ventricle leads to a concentric hypertrophy. However, this does not always have to be present. Initially, the left ventricle is still able to overcome the pressure gradient at the valve and can thus maintain cardiac output (CPV). Progressive symptoms are usually primarily diastolic dysfunction with congestion of the lungs. Hypertrophy of the left ventricle increases the oxygen demand of the cardiac muscles. The wall tension of the ventricle increases and impairs the subendocardial blood flow. In addition, left ventricular baroreceptors may respond incorrectly, causing peripheral vasodilation (Herold 2018).

The causes of aortic valve stenosis are:

• Degenerative changes as a result of calcification: In industrialized countries calcification in older people > 70 years is now the most common cause of AS in older people with about 50%. In the bicuspid aortic valve, the stenosis develops already in earlier years (mostly between the age of 50 and 70 years), in the tricuspid valve it develops later between the age of 70 and 90 years.
• Congenital aortic valve stenosis: Younger adults often have a congenital aortic valve stenosis. This is usually a bicuspid valve.
• Subvalvular or supravalvular congenital aortic valve stenosis (very rare, e.g. Williams-Beuren syndrome)
• Inflammatory processes: Inflammations of different aetiology lead to a thickening of the pocket flaps and to a sticking of the commissures, which cause calcification in the further course. The stenosis is usually combined with aortic valve insufficiency. However, this cause is now rarely found in industrialized countries thanks to consistent antibiotic treatment.
• Z. n. Radio (Kasper 2015)

According to Schuler (2017), the course of AS is divided into 4 stages:

1. Stage A: Sclerosis of a tricuspid valve or presence of a bicuspid valve
2. Stage B (also known as progressive aortic valve stenosis): mild to moderate stenosis as shown in the echocardiogram
3. Stage C: There is a hemodynamically severe AS, but without symptoms
4. Stage D: A haemodynamically severe AS is found with symptoms

In healthy adults the size of the opening area is between 2.6 - 3.5 cm². Before there is a hemodynamic effect, the opening area must decrease to < 1.5 cm². In a high-grade one the opening area is defined by an opening area of < 1.0 cm² (may well be asymptomatic). The pressure gradient is therefore not a mandatory criterion for defining the functionality of aortic valve stenosis in patients with limited left ventricular function (Herold 2018).

As a rule, patients become symptomatic from an opening area of < 1.0 cm², a mean gradient of > 40 mmHg. This constellation usually occurs only in the 6th - 8th decade of life. In patients with bicuspid aortic valve the symptoms develop about 10 - 20 years earlier (Pinger 2019).

The so-called cardinal symptoms include (Kasper 2015):

• Dyspnea on exertion
• pektanginous complaints
• Syncopes

Due to the increasing congestion of the lungs, a:

• performance reduction
• Dyspnea.

By restricting the subendocardial blood flow due to the ventricular hypertrophy to:

• Angina pectoris.

Due to a false response of left ventricular baroreceptors to:

• Vertigo
• Syncope.

Furthermore:

• Cardiac arrhythmia
• sudden cardiac death during physical exertion (occurs almost only in symptomatic patients).

X-ray:

As long as the AS is in a compensated state, the heart is radiologically inconspicuous. According to Pinger (2019), it only occurs after decompensation has developed:

• Widening of the left heart by enlargement of the left ventricle
• Signs of congestion in the lungs with decompensation
• Detection of flap lime
• in valvular AS poststenotic dilatation of the ascending aorta
• rounded apex of the heart (aortal configuration)
• in the further course dilatation of the left atrium
• Possible mitral configuration in case of mitral valve involvement (secondary mitral insufficiency)

In MRI, the anatomy and function of the heart can be well assessed. The following values can be determined additionally:

• the pressure gradient over the stenosis
• the valve opening area using planimetry (However, the KÖF is in some cases clearly overestimated compared to the determination according to Gorlin: KÖF in the MRI 0.91 cm² vs. 0.64 cm² . The sensitivity and specificity for a KÖF < 0.8 cm² is 78 % and 89 %, respectively. [Pinger 2019])

Inspection and palpation:

• Cyanosis, more rarely pallor is found (Pinger 2019).
• Pulsus tardus et parvus (typical symptom, but - especially in elderly patients - rarely occurring).
• cardiac impulse broadened and lifting (according to Pinger [2019] also shifted to the left)
• systolic buzzing over the aorta and in the carotids

Auscultation: The leading symptom of aortic valve stenosis is a

• spindle-shaped rough systolicvalve
  • Punctum maximum in the 2nd ICR on the right parasternal side
  • with continuation into the carotids
  • separated from the 1st heart sound
  • the more severe the stenosis, the more the sound maximum is shifted to late systole
• early systolic ejection click (which is absent when the valve is immobile)
• attenuation of the aortic portion of the 2nd heart sound in high-grade stenosis
• the 2nd heart sound is split respiratory variably
• the 2nd heart sound may show paradoxical splitting in high-grade stenosis
• diastolic in concomitant aortic valve regurgitation

ECG:

Changes are not found in the ECG until higher-grade stenosis. However, signs of hypertrophy may be absent even in severe AS.

• Left type
• Signs of left hypertrophy (Sokolow- Lyon index: SV1 + RV5 or RV6 > 3,5 mV)
• T- negation left precordial V4- 6 as sign of pressure hypertrophy.

Stress ECG (Pinger2019):

In aortic valve stenosis, the stress ECG cannot be used to diagnose CAD. It is used here only to confirm the presumed symptoms independent of exercise.

In patients with definite symptoms of AS, there is no indication to perform a stress ECG....

BNP:

The BNP- value plays a major role with regard to life expectancy (see below under prognosis) and should therefore be determined by laboratory chemistry (Pinger 2019).
Magnetic resonance imaging

Echocardiography / Doppler

In case of stenosis, the so-called pressure gradient is determined by echocardiography. For the aortic valve:

• the pressure gradient depends on both the pumping function of the ventricle and the valve opening area (Herold 2018).

The individual examination steps (Pinger 2019):

• Quantify the stenosis using the maximum instantaneous and mean pressure gradient across the valve (the maximum instantaneous and mean pressure gradient is calculated from the measured maximum and mean flow velocity, respectively, using the modified Bernoulli equation [Pinger 2019]).
• Calculation of valve aperture area (there are 3 different possibilities here:
  • 1. by means of the continuity equation (A1 x V1 = A2 x V2)
  • 2. by transthoracic planimetry
  • 3. by transesophageal planimetry
• Size measurement of all atria and ventricles (high-grade stenosis is possible even in the absence of hypertrophy (Pinger 2019))
• assessment of possible involvement of the other valves
• the pressure conditions in the small circuit should be estimated
• the maximum flow velocity, mean gradient, and valve orifice area (KOF) should always be reported (Pinger 2019)

Special attention should be paid to the following findings:

• Abnormality of the pockets (bi- or tri-cuspid).
• calcified or fibrotic thickened aortic valve pockets
• in case of calcifying AS, a reduced valve separation is found
• if the valve is only slightly calcified, there may be a dome-shaped dome position of the pockets during systole
• concentric hypertrophy of the left ventricle
• evidence of concomitant aortic valve regurgitation by reflux on color Doppler
• any dilatation of the ascending aorta (usually occurs in association with a bicuspid valve).

The severity of stenosis is classified as mild, moderate, or severe depending on the valve opening area and gradients across the valve (Herold 2018).

Mild AS:

• KÖF > 1.5 cm²
• mean pressure gradient < 25 mmHg
• Flow velocity < 3 m/s

Moderate AS:

• PPS 1.0 cm² - 1.5 cm²
• mean pressure gradient 25 - 40 mmHg
• flow velocity 3 - 4 m/s

Severe AS:

Echocardiographically, according to Pinger (2019), the following criteria are found in high-grade arterial valve stenosis:

• valve orifice area < 1.0 cm² or < 0.6 cm²/ m² (in relation to body surface area)
• the mean pressure gradient is > 40 mmHg
• maximum flow velocity is > 4.0 m/ s (in patients with normal transvalvular flow or normal HZV)
• velocity ratio < 0.25

Coronary angiography: Coronary angiography is indicated when coronary artery disease is also suspected. This applies to approximately 35% of patients with aortic valve stenosis (Bonzel 2009). In 2019, this number is already up to 50% of cases (Pinger). According to ESC, there is a preoperative indication for coronary angiography in (Pinger 2019):

• anamnestically known CHD
• Dysfunction of the left ventricle
• V. a. myocardial ischemia
• Postmenopausal women and men > 40 years of age.
• presence of at least one cardiovascular risk factor
• secondary mitral regurgitation for evaluation

The indication for retrograde probing of the aortic valve should be made carefully, as the risk of embolism may be as high as 22% (Omran 2003).

Manometry: Pressure measurements should include calculation of systolic (peak-to-peak) and mean gradient across the valve (measured between the left ventricle and aorta) and valve orifice area.

• peak-to-peak gradient: This represents the pressure difference between maximum systolic pressure in the left ventricle and maximum systolic aortic pressure. It cannot be measured accurately by Doppler sonography because the peaks do not exist at the same time and thus a measurement of the pressure difference cannot actually be measured.
• Maximum instantaneous gradient: This refers to the instantaneous maximum pressure difference between the systolic pressure in the left ventricle and the systolic aortic pressure. This is measured during simultaneous registration.
• Mean gradient: Mean gradient is an area integral between the left ventricular pressure curve and aortic pressure curve, also during simultaneous registration.

The gradient depends on the degree of stenosis, but also on the blood flow across the valve and thus the HZV. If ventricular function is impaired, a low gradient is found, but a relevant stenosis may still be present. In this case, the valve orifice area (CoeF) plays an important role. It can be calculated using the Gorlin formula.

The classification of an AS is not uniform in the literature (Herold 2018).

Graduation of the severity of an AS according to the pressure gradient (Krakow 2005):

• Grade I < 40 mmHg
• Grade II 40 - 80 mmHg
• Grade III 80 - 120 mmHg
• Grade IV > 120 mmHg

Classification of severity according to valve opening area (Krakow 2005):

• mild: > 1,5 cm²
• moderate 0,8 - 1,5 cm²
• severe 0,4 - 0,7 cm²
• critical < 0,4 cm²

Graduation of severity according to maximum transvalvular flow velocity:

• mild AS < 3.0 m/s
• moderate AS 3,0 - 4, 0 m/s
• severe AS > 4.0 m/s

(Herold 2018)

"Low-gradient" aortic valve stenosis.

"Low-gradient" aortic valve stenosis presents a particular challenge in terms of grading the severity of AS for the investigator, and thus for guiding optimal therapy.

Low flow in combination with a low gradient can be a consequence of systolic and diastolic dysfunction in high-grade aortic valve stenosis as well as a consequence of intermediate-grade stenosis associated with a nonvalvular cause (a so-called pseudoaortic valve stenosis). Because only patients in the first group would benefit from aortic valve replacement, differentiation between the two causes is important (Herrmann 2013).

Patients with pseudoaortic valve stenosis, whose cause is dilated cardiomyopathy, would not benefit from surgical valve replacement; rather, valve replacement is associated with high mortality in this patient group. Therefore, differentiation between pseudostenosis and severe aortic valve stenosis is crucial for further therapeutic consequences. This is done by interventional enhancement of low flow, which is performed by stress echocardiography with dobutamine. In pseudostenosis, there is only a minimal increase in the transvalvular gradient with an increase in the size of the effective orifice area (EOA: effective orifice area).

In fixed aortic valve stenosis, on the other hand, there is an increase in the transvalvular gradient with a constant valve orifice area due to the catecholamine-induced increase in stroke volume.

(Schuler 2017)

• Mitral valve insufficiency
• Pulmonary Stenosis
• Ventricular septal defect

(Bob 2001)

• Cardiac arrhythmia
• Left heart failure
• sudden cardiac death (20%)

(Herald 2018)

Until 2002, the treatment of symptomatic aortic stenosis was exclusively surgical. After A. Cribier introduced catheter-assisted implantation, valve replacement by TAVI was initially performed exclusively on inoperable patients or patients at high risk of surgery.

In the meantime, however, randomized, controlled studies of patients with intermediate risk have also been conducted. These studies have shown that TAVI is equivalent to surgical valve replacement. However, TAVI is associated with more vascular complications, paravalvular leakage and pacemaker implantation. On the other hand, the surgical group had more general bleeding complications, acute renal failure, and unknown atrial fibrillation.

These studies were included for the first time in the 2017 update of the ESC guidelines and subsequently transfemoral TAVI was issued as a Class I b guideline recommendation for patients at intermediate risk and thus equated to surgical therapy.

(Ince 2018)

According to the ESC guidelines of 2017, the following conditions are present in aortic valve stenosis

1. evidence level IB:

- in symptomatic patients with severe AS, surgical removal of the stenosis should be performed immediately

2nd evidence level IC:

- symptomatic patients with relevant low-flow, low-gradient stenosis and reduced left ventricular function

- asymptomatic patients with severe aortic stenosis and reduced systolic function of the left ventricle (EF < 50 %) without other causes

- asymptomatic patients with severe aortic stenosis and the appearance of symptoms during the stress test

3. evidence level IIaC:

- symptomatic patients with relevant low-flow, low-gradient stenosis while maintaining left ventricular function

- asymptomatic patients with severe aortic stenosis and medium to highly calcified aortic valve as well as rapid hemodynamic progression (i.e. increase in aortic valve V max> 03, m/s/year)

- asymptomatic patients with severe aortic stenosis and a drop in blood pressure below the baseline value at the stress test

- asymptomatic patients with severe aortic stenosis and high BNP (B- natriuretic peptide)

(Herald 2019)

Symptomatic patients can choose between surgery and TAVI. The decision on this should always be based on individual risk assessment.

Surgery should rather be considered in patients with a low risk of surgery (STS or EURO score II < 4 %, recommendation class IB)

TAVI is recommended for patients with medium or high risk (STS or EURO score II ≥ 4%, recommendation class IB)

The decision of a TAVI should - in the case of patients not suitable for surgery - be made jointly by the Heart Team (cardiology, cardiosurgery, cardiac anesthesia).

(Herald 2019)

TAVI is not recommended for asymptomatic patients. In this case, the procedure is always surgical. However, if the above mentioned additional criteria are not fulfilled in asymptomatic patients, one can wait carefully and proceed according to the above mentioned ESC Guidelines (Herold 2019).

Patients with severe AS should avoid major efforts and competitive sports. Dehydration or hypovolemia must also be avoided at all costs, as otherwise there may be a significant reduction in stroke volume (Kasper 2015).

In the case of a proven severe aortic valve stenosis with exclusion of pseudoaortic valve stenosis of the so-called "low- gradient" aortic valve stenosis, a drug therapy of the accompanying heart failure is not effectively possible. The only therapeutic measure is surgical intervention (Herold 2018).

The situation is different with drugs used to treat hypertension or coronary heart disease. Beta-receptor blockers and ACE inhibitors can be given to asymptomatic patients without any problems, as can nitrates (Kasper 2015). In a retrospective study, patients with degenerative calcifying aortic valve stenosis showed slower progression of both calcification and opening area decrease in a retrospective study with HMG-CoA-reductase inhibitors (statins). However, this result could not be reproduced in randomized prospective studies. Nevertheless, the use of statins is recommended (Kasper 2015).

For more details on the surgical measure see below valve replacement

Follow-up examinations are recommended every 3 years for patients with mild and until then asymptomatic AS. In the case of more severe, but previously asymptomatic courses of AS, follow-up examinations should already take place at 6 to 12-month intervals (Herold 2018). The pressure load caused by stenosis of the valves is much more stressful for the heart than the volume load caused by valve insufficiency. Therefore, a stenosis of the heart valves generally has the less favourable prognosis. Nevertheless, approx. 50% of patients remain asymptomatic for years - despite severe stenosis. However, closer anamnestic questioning often reveals that the patients unconsciously spare themselves physically and thus prevent any possible symptomatology (Herold 2018).

The BNP value plays a major role in life expectancy (Pinger 2019). In patients with a high-grade aortic valve stenosis at low pressure gradient, the 1-year survival rate is:

• 47 % with a BNP of > 550 pg / ml
• 97 % with a BNP of < 550 pg / ml

Therefore, the BNP value should always be determined in patients with AS.

Overall it can be said that patients with AS without symptoms have a good prognosis. However, as soon as the patients become symptomatic, the 2-year survival rate without surgical intervention is < 50%. From the onset of symptoms until death it takes a natural course (Kasper 2015):

• for angina pectoris 3 years
• Syncopes 3 years
• Dyspnea 2 years
• Heart failure 1.5 - 2 years

The mortality rate for a surgical valve replacement is approximately 3 % and increases to approximately 6 % with simultaneous coronary artery bypass grafting (CABG) (Herold 2018).

According to the latest guidelines, there is no longer an indication for endocarditis prophylaxis in patients with aortic valve stenosis that has not been treated surgically by then (Herold 2018). The only exception is endocarditis that has already taken place in the medical history (Kasper 2015).

After valve reconstruction or a prosthetic heart valve, however, there is a significantly increased risk of endocarditis (cave: prophylaxis with medication necessary: the post-procedural bacteremia frequency after tooth extractions in gingivitis is up to 90%. For this reason, endocarditis prophylaxis is necessary postoperatively for certain procedures. The standard therapy is administered as a single dose approx. 30-60 minutes before the procedure, e.g. amoxicillin or ampicillin 2 g orally or i.v., or in the case of penicillin allergy clindamycin 600 mg also orally or i.v. (Pinger 2019).

For further details see Endocarditis prophylaxis

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