Subaortic stenosis in the dog

Subaortic stenosis is the second most common congenital disease in the dog, with a prevalence of 25.5%; it is characterized by fibrous lesions which surround, entirely or partially, the subvalvular part of the left ventricular outflow tract (LVOT).

AETIOLOGY

Subaortic stenosis is more common in large or giant breeds. The breeds predisposed are the German Shepherd, Boxer, Newfoundland, Golden Retriever and Rottweiler, suggesting a genetic component in the transmission of the disease. The pathology has, however, also been described in other breeds, while mongrels seem to be less affected.

Genetic transmission of subaortic stenosis has been confirmed only in Newfoundland dogs, even if it is considered at the basis of transmission also in other breeds. The modality of transmission has not been precisely defined, and probably cannot be explained by classic Mendelian genetics. It has been suggested that there is a polygenic mode of transmission, subject to modifications by other genes or the environment.

PATHOLOGY

The subvalvular lesion is fibrous or fibro-cartilaginous. It can vary from small subvalvular nodules, in the milder forms, to complete stenotic rings which surround the subvalvular region of the LVOT. In the more severe forms there may be ‘tunnel lesions’, which occupy an extensive part of the LVOT (Fig. 1). In a study on Newfoundland dogs by Pyle and Patterson, the lesions were classified into three grades depending on their severity: grade 1, small nodules on the endocardial surface just under the valve; grade 2, a thin endocardial ring which extends partially into the LVOT; grade 3, a fibrous band or thick ring which encircles the entire LVOT.

It has been shown that the lesions in Newfoundland dogs do not appear before the third week of life. It has, therefore, been hypothesised that subaortic stenosis is not a purely congenital disease, but rather that flow alterations, secondary to changes in LVOT morphology, may cause the proliferation of subvalvular fibrous lesions. A recently proposed theory is that a steeper aortoseptal angle may predispose to septal proliferation as a consequence of shear stress, and indeed the aortoseptal angle in Boxers with subaortic stenosis is steeper than that in healthy Boxers.

Not infrequently, aortic lesions are associated with malformations of the mitral valve. A form of dynamic stenosis associated with mitral dysplasia has, in fact, been described in Dalmatians and Retrievers.

PATHOPHYSIOLOGY

Subvalvular lesions cause narrowing of the LVOT, with a consequent increase of the afterload. The myocardium responds to load alterations with concentric hypertrophy, which then causes an increase of the ventricular mass and a reduction in the diastolic volume of the left ventricle. Histologically, hypertrophy is accompanied by atherosclerotic alterations of the intramural coronary arteries, with stenosis of the vessels caused by deposition of hyaline substance and interstitial fibrosis. These histological abnormalities may be followed by ischaemic lesions which are probably the underlying cause of the arrhythmic events that often appear in patients with subaortic stenosis.

Concentric hypertrophy initially causes diastolic dysfunction, which can result in left congestive heart failure, due to the increased ventricular and atrial end-diastolic pressures. The subendocardial ischaemia, which appears following the inappropriate hypertrophy and the above mentioned vascular lesions, may favour the development of ventricular arrhythmias, which can, in some cases, be fatal.

Rarely, subaortic stenosis may evolve into an end-stage form called “afterload mismatch”. This is a peculiar condition characterized by eccentric hypertrophy and systolic dysfunction. It occurs when the left ventricle, subject to chronically increased wall stress, is no longer capable of maintaining an adequate output. Initially the eccentric hypertrophy is successful in compensating for this deficit; however, when the increase in preload is also no longer adequate, the stage of “afterload mismatch” is reached (Fig. 2).

Finally, it is important to recall that dogs affected by subaortic stenosis are predisposed to the development of bacterial endocarditis. Although this is a rare event, antibiotic prophylaxis is recommended for these patients.

DIAGNOSIS

Clinical diagnosis

Most dogs with subaortic stenosis are asymptomatic, independently of the severity of the disease. The diagnosis is clinical, based on the recognition of a systolic murmur, and then confirmed by echocardiography. Subaortic stenosis may develop until after 1 year of age and it is, therefore, advisable to monitor dogs predisposed to the disease over time, even if no murmur is present in the puppy.

The intensity of the murmur is variable; it is audible at the 4^th left intercostal space and may radiate to the neck and to the right. In severe forms the femoral pulse may be weak and slow, but is often normal.

It should be noted that the presence of a murmur is not necessarily indicative of the disease. A considerable percentage of Boxers have a systolic murmur and a slightly increased aortic flow velocity, without having subvalvular lesions. It has been hypothesised that a different LVOT morphology may be the cause of the murmur in such subjects.

Radiography

Radiography of the chest is often normal, as the concentric hypertrophy of the ventricle does not alter the cardiac silhouette. In cases in which there is a post-stenotic dilatation, there may be “bulging” of the aorta, visible as a dilatation of the aortic root at the 1:00-2:00 o’clock position in a dorso-ventral projection. In patients with more severe subaortic stenosis, left atrial dilatation can be identified and eventually signs of left congestive heart failure.

Electrocardiography

In dogs with subaortic stenosis the electrocardiographic tracing is often normal. In more severe cases the tracing can show signs of left ventricular hypertrophy, ventricular ectopic complexes or ST-segment elevation, a sign of ischaemic damage.

Echocardiography

Echocardiography is the first-line examination for the diagnosis and staging of subaortic stenosis. In most cases, two-dimensional echocardiography can identify the presence of subvalvular fibrous lesions (Figs. 3 and 4). Furthermore, with regards to visualisation of subvalvular lesions, the sensitivity of transthoracic echocardiograpy appears comparable to that of transoesophageal echocardiography.

Doppler echocardiography can determine the pressure gradient through the stenotic ostium with a good level of precision. Starting from the maximum aortic flow velocity and using a modified Bernoulli equation it is possible to calculate the pressure gradient between the left ventricle and the aorta. Subaortic stenosis is considered to be mild if the pressure gradient is <40 mmHg, while it is severe when the gradient is >80 mmHg. The accuracy of the Doppler measurement depends on the alignment with the flow to be measured. In view of this, a subxiphoid view is suggested for the measurement of the aortic flow since, in most dogs, this allows for better alignment with the LVOT.

Subaortic stenosis is often associated with aortic valve regurgitation, which is probably related to lesions of the valve leaflets, caused by the turbulent flow.

TREATMENT

There is still no scientific evidence on the efficacy of any drug for the treatment of subaortic stenosis in the dog. However, based on data published in literature, albeit on limited populations, and based on the experience of most veterinary cardiologists, treatment with β-blockers may be beneficial in severe cases. In a retrospective study by Kienle et al., dogs treated with a β-blocker survived longer than untreated patients. This statement must clearly be considered bearing in mind the limitations of a retrospective study. By reducing contractility and heart rate, β-blockers (propranolol or atenolol) reduce myocardial oxygen requirement. This may reduce the risk of ischaemia, the risk of developing ventricular arrhythmias as well as the risk of sudden death. Furthermore, the negative chronotropic effect of b-blockers increases the duration of diastole and, consequently, coronary filling, which in patients with subaortic stenosis may be strongly compromised by the concentric hypertrophy and remodelling of intramural coronary arteries.

As previously mentioned, prophylactic antibiotic therapy for bacterial endocarditis is recommended in all cases of subaortic stenosis.

In cases in which the disease evolves into left heart failure, the recommended therapy is that used for heart failure  (diuretics, ACE-inhibitors, spironolactone). The use of positive inotropic agents (pimobendan, dopamine, dobutamine) is strongly contraindicated in dogs with subaortic stenosis, as the increase in contractility would increase myocardial work without a corresponding increase in cardiac output, because of the fixed stenosis.

Surgical therapy

Over the years various surgical techniques have been proposed for the treatment of subaortic stenosis. Based on the studies published in literature, all the treatments proposed (balloon valvuloplasty, fibrous ring resection, septotomy) lead to an immediate improvement of the pressure gradient and, in some cases, of symptoms. However various studies have found that the survival of dogs treated surgically is the same as that of dogs treated with β-blockers. In view of this, surgery is not currently recommended for the treatment of subaortic stenosis.

BREED SCREENING

Screening programmes have been implemented for many years, with the collaboration of breeders, with the goal of reducing the incidence of subaortic stenosis in breeds particularly at risk. The selection must be made carefully, with the aim of eliminating the disease while at the same time minimising consequences on the genetic pool of the breed.

Furthermore, the diagnosis of subaortic stenosis must be made with particular attention. In subjects with a mild form, with subvalvular lesions which are not convincingly visible at echocardiography, or with a border-line aortic flow velocity, a second examination after some time may be necessary to make the final diagnosis.

In 2000, Bussadori et al. proposed some guidelines with the goal of standardising the diagnostic criteria for subaortic stenosis. Subvalvular lesions should be classified morphologically using the classification described by Pyle and Patterson for Newfoundland dogs (see the Pathology section above). Lesions are already visible at 6-8 weeks of life, although they can evolve until 12-15 months of life so it is not possible to exclude or include subjects in a breeding programme until after the first year of life. In terms of the echocardiographic examination, the staging of subaortic stenosis is based on the flow velocity at the LVOT, measured with pulsed or continuous wave Doppler examination in a retrosternal view. The aortic flow is considered normal if it is laminar and has a velocity < 2 m/sec. Subaortic stenosis is classified as follows:

• MILD: peak pressure gradient between 20-49 mmHg (corresponding to an aortic flow velocity  of 2.25-3.5 m/sec).
• MODERATE: peak pressure gradient between 50-80 mmHg (corresponding to an aortic flow of 3.5-4.5 m/sec).
• SEVERE: peak pressure gradient greater than 80 mmHg (corresponding to an aortic flow velocity greater than 4.5 m/sec).

In Boxers an aortic flow velocity < 2.15 m/sec is considered normal, although velocities between 2.2 and 2.5 m/sec have also been reported in normal subjects. A new classification system, based on the presence of a murmur and  B-mode and Doppler echocardiographic findings, has recently been proposed for Boxers undergoing screening for subaortic stenosis.

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