Aortic isthmus stenosisQ25.1

The clinical picture of aortic coarctation (CoA) was first described in 1760 by Giovanni Battista Morgagni (Kische 2011).

Aortic isthmus stenosis (CoA) is an organic stenosis of the thoracic aorta at the physiological narrowing between the A. subclavia sinistra outlet and the aortic orifice of the Ductus Botalli.

The CoA is not only a circumscribed narrowing of the aorta, it is also part of a generalized arteriopathy (Herold 2019).

The stenosis occurs as an externally visible indentation of the posterior wall of the aorta and also as a thickening of the vascular wall in the area of the media and intima caused by proliferation, so that the constriction of the lumen is far greater than would be suspected purely externally (Apitz 2002).

Associative anomalies are often found:

• Bicuspid aortic valve (occurs in up to 85 % of cases)
• Ventricular septal defect
• Mitral valve anomaly
• intracranial aneurysm in the area of the Willisii Circulus (occurs in up to 10% of cases [Kasper 2015])
• Ulrich Turner Syndrome
• Williams-Beuren syndrome
• Neurofibromatosis
• Cystic median necrosis Gsell- Erdheim (necrosis in the area of the ascending and descending aorta)
• Hypoplastic left heart syndrome
• D- TGA (dextro- transposition of the major arteries)
• Subaortic stenosis
• Atrial septal defect
• AV channel
• trisomy 21
• Shone Complex
• Ellis van Creveld syndrome
• Holt- Oram Syndrome
• Marfan syndrome (Apitz 2002)

The formerly common classification of pre- and postductal aortic coarctation as infantile or adult stenosis is considered obsolete and has been abandoned in the meantime, since the stenosis is usually located juxtaductally directly opposite the mouth of the ductus (Haas 2011). With regard to the extent of the stenosis a subdivision into:

• circumscribed or also discrete aortic isthmus stenosis
• tubular hypoplasia of the distal aortic arch

Aortic isthmus stenosis occurs in approx. 5 % - 8 % of all congenital cardiovascular malformations and is therefore one of the most frequent congenital viti (Kische 2011).

The incidence is therefore approx. 410 / 1 million live births (Pinger 2019).

Male newborns are affected twice as often as female newborns (Herold 2019).

The CoA is a congenital malformation. A reduced flow through the aorta in the embryonic period is discussed as a possible cause (Apitz 2002).

Pathophysiology: A relevant stenosis of the aorta leads to an increase of afterload of the left ventricle. This in turn leads to hypertrophy and thus to damage of the left ventricle. Depending on the severity of the stenosis the systolic pressure is more or less poststenotically decreased. This can lead to the formation of a collateral system via the subclavian, internal thoracic, thyrocervical, subscapular or anterior spinal artery. From there, the blood flows via the Aa. intercostales into the descending aorta and/or to the A. epigastrica superior via the A. epigastrica inferior or via the Aa. lumbales to the Aorta abdominalis (Pinger 2019).

The stenosis results in brachiocephalic hypertension and hypotension in the abdominal-femoral region, the severity of which is determined by the formation of the collaterals. (Herold 2019 / Kische 2011). The arterial systolic blood pressure is only affected from a stenosis level of 45-50%, the diastolic pressure increases prestenotically much later, I do not have more detailed information (Apitz 2002).

Arterial hypertension can occur exclusively unilaterally, namely when the right subclavian artery emerges as the lusoria artery (occurs in 3 % - 4 % of cases) or the left subclavian artery emerges distally from the stenosis or directly in the stenosed area. In this case there is a unilateral collateral formation and the arterial hypertension is found only on the left or only on the right arm (Kische 2011).

Sometimes the pathophysiology is also characterized by additional malformations (Pinger 2019).

Newborns with a critical form of CoA only have sufficient blood supply to the lower half of the body as long as the ductus arteriosus remains open. Once the ductus closes, rapid progressive heart failure develops. The following symptoms may occur:

• weakness in drinking
• Tachypnea
• Dyspnea
• Hepatomegaly
• grey-pale skin colour
• missing or weakened femoral pulses

If there is no appropriate therapy, left ventricular decompensation with secondary organ failure occurs and

• Signs of heart failure
• Renal insufficiency
• Acidosis
• Liver failure
• necrotizing enterocolitis (NEC) (Haas 2011 Guidelines)

On the other hand, the CoA can also show very good cardiovascular adaptation and is one of the most frequently overlooked cardiovascular abnormalities in both children and adults. It should therefore always be excluded by differential diagnosis in juvenile hypertensive patients (Stierle 2014). Typical symptoms of a CoA are:

• hypertonic blood pressure values in the upper half of the body (sometimes only unilaterally, see pathophysiology below) with a large blood pressure amplitude
• Symptoms of hypertension like:
  • Headaches
  • Nosebleeds
  • Tinnitus
  • Swindle
• low blood pressure in the lower half of the body
• the gradient between upper and lower extremities is > 20 mmHg
• warm hands and cold feet
• possibly Claudicatio intermittente

ECG

In newborns the ECG often shows few abnormalities (Haas 2011 Guidelines). For example, signs of right ventricular hypertrophy may be present (Sokolow- Lyon- Index: RV1 +SV5/6 > 1.05 mV etc.) (Herold 2018)

In adolescence, the ECG is often normal even in the case of significant aortic coarctation (Apitz 2002). In the further course of the disease it can occur:

• signs of left ventricular hypertrophy (Sokolow-Lyon index: SV1 + RV5 or RV6 > 3.5 mV [Herold 2018] and - Lewis index or index of the frontal plane (RI + S III - R III - SI = > + 1.6 mV [Klinge 2002])
• in 50 % of the adults, in addition to left ventricular hypertrophy, there is also a right thigh block-like picture (interpreted as an increase in neonatal right ventricular hypertrophy) (Apitz 2002)

Exercise ECG:

Under load can occur:

• changes in the ST- distance
• Changes of the T-wave (both unspecific signs of damage, so-called strain patterns [Stierle 2014])
• rapid frequency increase
• an increasing systolic blood pressure difference
• rapid fatigue (Apitz 2002)

Chest X-ray

An X-ray thorax is not required for the primary diagnosis (Haas 20111, guideline)

Otherwise, they may be present in the chest X-ray image:

• at the left mediastinal rim at the top a dilated left subclavian artery
• extended A. ascendens
• Notch of the aorta in the area of coarctation plus pre- and poststenotic dilatation of the aorta (the so-called 3-symbol or inverse epsilon sign [Herold 2019])
• Usures in the area of the 3rd - 9th rib (a typical sign in CoA, but not always present; occurs in 1-4 year old children only in 14 % of cases, in > 6 year old children > 70 % [Apitz 2002] ; the usures are caused by dilated collateral vessels, which lead to erosion of the lower ribs) (Kasper 2015)
• Calcifications in bicuspid aortic valves are possible
• Cardiomegaly in hypertensive heart disease (Pinger 2019)

MRI

This examination is the method of choice for serial follow-up (Pinger 2019) and postoperative control. However, it does not replace the diagnosis with a heart catheter before a planned operation (Stierle 2014). The following are quantifiable with MRT:

• Determination of the flow and gradients
• Representation of the associating collateral
• Length and severity of the stenosis (Kasper 2015)
• Presentation of associative malformations (Haas 2011 Guidelines)

Echocardiography

Echocardiography provides a good assessment of the morphology, the location of the stenosis and its extent, as well as associative cardiac abnormalities and the function of both ventricles or atria (Herold 2019). In infants and toddlers, suprasternal imaging in the 2-D echo is still successful, later a TEE should be performed for precise diagnosis (Stierle 2014).

Typical findings with CoA are:

• Thickening of the left ventricular posterior wall (in critical CoA)
• Dilatation of the left ventricle
• dorsolateral notch and wedge-shaped compression with poststenotic dilatation after the left subclavian artery has left the body (hemodynamically relevant is the constriction from < 4 mm diameter) (Apitz 2002)
• Quantification of the stenosis
• Determination of the pressure gradient across the CoA using the extended Bernoulli equation

In the case of tubular hypoplasia, however, it should be noted that the Doppler gradient is measured too high (Apitz 2002)

• peripherally of the stenosis there is a turbulent flow pattern with increased flow velocity and a diastolic "run- off" (typical sawtooth curve in the Doppler flow curve [Haas 2011, guideline]); in higher grade stenosis there is also a diastolic flow above the stenosis and a forward flow into the abdominal aorta.

Cardiac catheter examination

The cardiac catheter examination is dispensable with regard to the diagnosis. However, there is an indication for planned interventional therapy (angioplasty or stenting) (Haas 2011, guideline), as well as for the visualisation of coronary arteries in coronary artery disease, which often occurs early and accelerated in this clinical picture [Stierle 2014] (Kasper 2015).

In infants with critical CoA and moribund condition, the examination shows a significantly higher risk and should therefore be discussed with the surgeon in each individual case (Apitz 2002).

Otherwise, the following statements can be made during the cardiac catheter examination:

• the anatomy in the area of the aorta and supra-aortic vessels
• above the isthmus region Determination of the pressure gradient
  • if no major collaterals are present, a CoA is considered significant at an invasive peak-to-peak gradient of > 20 mmHg
  • the systolic pressure in the ascending artery is increased
  • the arterial pressure distal to the CoA shows a small pulse amplitude
  • even with higher grade stenoses, however, no significant gradient can be measured - provided there is a pronounced collateralization
  • in addition, an increase in the peripheral vascular resistance of the lower half of the body often occurs secondarily, as a result of which the difference in arterial pressure between the upper and lower half of the body decreases and the degree of severity can be underestimated ( Stierle 2014)
• associated cardiac abnormalities can be detected or excluded
• Assessment of left ventricular function
• Statements on the status of the coronary vessels
• Simultaneous stent implantation and/or balloon angioplasty (Herold 2019)

Inspection and palpation

• Femoralis and foot pulses are only weakly palpable
• in the area of the back, the lateral thoracic wall or intercostal a collateral circulation can be palpated
• the apex of the heart is widened, lifting but not displaced (in concentric left hypertrophy)
• Visible pulsations of the jugulum and carotid
• Pulsus durus (hard, taut pulse)
• Pulse difference between the right and left arm (if the stenosis is located before the exit of the left subclavian artery)
• Pulse difference between the right arm and the femoral artery (Stierle 2014)

Auscultation

In newborns with critical CoA, a heart murmur is usually absent.

In older children are typical:

• late systolic murmur with p. m. between the scapulae and infraclavicular; occasionally auscultated in the region of the abdominal aorta
• continuous flow noise in the back (caused by collaterals between the upper and lower half of the body) (Haas 2011 Guidelines)

Other auscultation findings that may occur in the course of the procedure are:

• the second heartbeat is split with loud closing of the aortic valve (click)
• aortal ejection tone (in case of aorticectasia, bicuspid aortic valve or hypertension)
• Following aortic valve closure, a diastolic decrescendo noise is found (occurs in aortic valve insufficiency as a result of bicuspid aortic valve) (Herold 2019)

Blood pressure measurement

Blood pressure should be at

• all 4 extremities are measured
• under stress
• 24- h blood pressure measurement

In the case of long-term hypertension, regular ophthalmological check-ups should also be performed (Haas 2011 Guidelines).

• arterial hypertension of other genesis
• In juvenile hypertension, all forms of secondary hypertension must always be excluded. Hypertension in this group of patients can only be described as "essential" after all causes have been excluded.

Conservative therapy

An effective conservative treatment is not available at the CoA. The goal is always the operative measure at the lowest risk and at the earliest possible time.

In newborns with a critical form of CoA, recompensation is sometimes necessary as a preparatory measure for surgery. These may include:

• Infusions with prostaglandin E (0.01 - 0.03 (-0.1) µg / kg / min) to reopen the duct
• Compensation of a possible acidosis with sodium bicarbonate
• Catecholamines (Dopamine, Suprarenin)
• Diuretics (furosemide, spironolactone)
• Fluid restriction
• Digitization
• Intubation and machine ventilation (Apitz 2002)

Patients who have been asymptomatic up to now with only slight stenosis, a low pressure gradient and without arterial hypertension can initially be monitored regularly (Pinger 2019).

The treatment of a CoA should only be carried out in centres that have sufficient experience with congenital heart defects. (Herold 2019). The indication for surgical treatment is given:

• regardless of the symptomatology in
  • Patients with non-invasive gradient > 20 mmHg between upper and lower extremity and arterial hypertension with RR values of < 140 / 90 mmHg in adults
  • Pathological blood pressure under stress
  • significant left hypertrophy
• independent of the pressure gradient at
  • Patients with arterial hypertension and a diameter of the stenosis measured in CT, MRT or angiography at diaphragmatic level < 50% of the aortic width
• Patients with significant associative aortic valve insufficiency or stenosis
• Presence of a descending aortic aneurysm with a diameter > 50 mm (27.5 mm / m² BSA)
• Aneurysm of the descending aorta with rapid growth
• Presence of aneurysms in the former isthmus region
• large or symptomatic aneurysms of the Circulus Willisii

The indication for surgical intervention is given according to ESC 2010:

• Indication class I: Patients with a non-invasively measured blood pressure difference of > 20 mmHg between the upper and lower extremities in case of arterial hypertension (blood pressure measured in the arm is > 140 / 90 mmHg), pathological hypertension under stress or significant hypertrophy of the left ventricle
• Indication class IIa: Hypertensive patients - independent of the pressure gradient - with a stenosis ≥ 50 mmHg
• Indication class IIb: Non-hypertensive patients - independent of the pressure gradient - with a stenosis ≥ 50 mmHg (Pinger 2019)

The operation should be performed on children as early as possible after the diagnosis. If the operation is performed after the pre-school age, the risk of persistent hypertension increases.

Adults should also be operated on as soon as possible after the diagnosis has been made. Surgery after the age of 30 or 40 is more likely to result in higher surgery mortality due to the degenerative changes in the aortic wall. In addition, organ damage due to arterial hypertension may have already occurred by this time, and there may be coronary heart disease, mitral valve anomalies or coexisting aortic valves.

Surgical procedures are available:

• Resection of the stenosed portion and subsequent end-to-end anastomosis
• Resection and bridging by a prosthesis interposition
• Direct isthmus plastic surgery according to Vossschulte as an alternative procedure to classical resection (Borst 1991)
• indirect isthmus plastic according to Vossschulte (also known as patch plastic; however, it can only be used for very short stenoses which are conveniently located [Borst 1991])
• Creation of a prosthesis bypass
• Subclavian grafting according to Waldhausen (used particularly frequently in infancy [Borst 1991])

The indications for balloon angioplasty with or without stent implantation are:

• native aortic isthmus stenosis with appropriate anatomy (therapy of choice)
• Residual stenoses or also restenoses from a previous operation

Nowadays, catheter-interventional treatment with stent implantation has become widely accepted in adults - provided the anatomy is suitable - as well as for the treatment of recurrence. A multicenter observational study by Forbes (2011) showed that patients after stent implantation have fewer complications than patients after balloon angioplasty or surgical therapy (Pinger 2019).

Immediate surgical complications:

• within the 1st - 2nd week postoperatively, excessive, paradoxical arterial hypertension may occur
• necrotizing aortitis mesenterialis or mesenteric infarction can cause an acute abdomen
• a disturbance of the spinal blood flow can lead to a spinal cord lesion with the risk of paraplegia
• the surgery lethality is < 2 % (Stierle 2014)

Life expectancy is reduced even with early surgery - compared to the normal population. Causes of death are mainly arterial hypertension and cardiovascular complications.

After 10 years the survival rate is about 90%, after 20 years about 85% and after 30 years about 70%. In older studies the average age at death due to late complications is 38 years.

Postoperatively the following complications can occur:

• persistent arterial hypertension (see below)
• accelerated atherosclerosis
• Re- Stenosis
• Development of an aneurysm (occurs in up to 30% of cases with resection and patchplasty)(Pinger 2019)
• coronary heart disease
• Aortic valve sclerosis
• Aortic valve stenosis or insufficiency (for bicuspid valve)
• Mitral valve prolapse with valve malfunction
• bacterial endocarditis (mostly in the presence of a bicuspid valve [Pinger 2019])
• Rupture of aneurysms (e.g. aortic or cerebral aneurysms)

Postoperative hypertension

Systemic hypertension, which often develops postoperatively, can occur without the presence of residual coarctation. However, it is related to the duration of the preoperative hypertension (Kasper 2015). In 1/3 of the patients, the hypertension recedes in the 1st postoperative month and in 2/3 in the 1st postoperative year [Stierle 2014]). When measuring blood pressure, special care must be taken to ensure that the values are measured both at rest and under stress, as excessive systolic blood pressure values often only become apparent under stress. This is attributed to diffuse vasculopathy and a lack of compliance of the stenting or operated region (Kasper 2015).

Aftercare:

A lifelong follow-up should be performed every 6 - 12 months, even after a successful curative surgery. For follow-up, the performance of an MRI and a screening for intracerebral vascular anomalies are particularly recommended (Stierle 2014).

Endocarditis prophylaxis:

Endocarditis prophylaxis is generally NOT necessary in patients with aortic isthmus stenosis (Muntau 2018). However, if they fall into the group of high-risk patients (e.g. due to endocarditis, after valve replacement, etc.) endocarditis prophylaxis must be taken.

Therapy recommendation (only for high-risk patients):

• administer antibiotic prophylaxis 30 - 60 min before the procedure as a single dose
• if oral administration is possible, amoxicillin or ampicillin 2 g p. o. may be administered
• if oral administration is not possible, ampicillin or cefalexin 2 g i.v. is recommended
• for ampicillin or penicillin allergy, clindamycin 600 mg should be given orally
• with necessary i.v. administration Clindamycin 600 mg i.v.

Please note that cephalosporins must not be used in patients who have reacted with anaphylaxis, angioedema or urticaria after ampicillin or penicillin (see below cephalosporins; penicillin allergy, cephalosporin allergy)

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