Case Studies In Small Animal
Text from "Small Animal Cardiovascular Medicine"
Clinical signs in puppies, almost all mild to moderately affected individuals, and many severely affected individuals are absent. Most owners report a normal and apparently healthy individual when presenting the dog for routine examination. A heart murmur may have been previously identified in some dogs and may have been regarded as an innocent or functional murmur in a young puppy. More severely affected animals may be presented for exertional fatigue, syncope, or rarely for signs referable to congestive left heart failure. Sudden death without premonitory signs is common.
The physical examination is often unremarkable except for the presence of a systolic ejection murmur, usually loudest in the left basilar region. The murmur intensity roughly correlates with lesion severity with mildly affected dogs having a I-III/VI murmur and more severely affected individuals having a IV-V/VI murmur. The radiation of the murmur, if present, is often characteristic. The murmur tends to radiate toward the left apex, and the right cranial thorax. It might also be heard over the carotid arteries upon auscultation of the cervical region on either side of the trachea. In many dogs, the murmur is equally loud at the right cranial thorax and left basilar region and in some it is loudest or only present at the right cranial thorax. Due to the developmental nature of fixed subaortic stenosis, the murmur may increase in intensity during the first months of life. In dogs with a dynamic component, the murmur is similar but may vary in intensity from one examination to the next. In dogs with a severe obstruction, the arterial pulse may be hypokinetic (i.e., the pulse pressure is decreased) with a tardy or delayed peak (pulsus parvus et tardus) although pulse pressure may remain normal. Occasionally, a diastolic murmur associated with mild to moderate aortic insufficiency is also audible in the left basilar region.
The electrocardiogram is often normal in dogs with SAS, either fixed or dynamic. Left ventricular enlargement is suggested by the presence of an increased R wave amplitude in leads II and aVF or the left chest leads in some dogs. The mean electrical axis is usually normal although a left axis deviation may be rarely identified. The ST segment may be slurred, depressed, or elevated in some dogs with severe SAS. This is usually secondary to regional myocardial hypoxia. Ventricular premature contractions may also be identified in dogs with pressure gradients in the severe range. The latter findings may be induced or exaggerated by exercise.
Some veterinary cardiologists advocate long-term ambulatory ECGs (i.e., Holter monitor recordings) in patients with moderate to severe SAS to detect ventricular arrhythmias and ST segment changes that might suggest an increased probability of sudden death. In a report of 14 dogs with SAS evaluated by Holter monitor, ventricular premature complexes were recorded in 10 that were multiform in 7. Some dogs had ventricular tachycardia, triplets or couplets. Although there was a tendency for the frequency of ventricular arrhythmias to increase in dogs with higher pressure gradients, considerable overlap occurred between the groups. Ventricular premature complexes were only identified on the surface electrocardiogram in 3 of 11 dogs in this study. When Holter recording was repeated 1 month after prescribing atenolol in 4 of the dogs, the frequency of ventricular premature contractions had decreased by 75%. ST segment deviation, probably related to regional myocardial ischemia was identified in 50% of these dogs and developed more often in dogs with higher pressure gradients.
Thoracic radiographs are typically normal in mildly affected individuals and may show only apparent mild cardiomegaly due to LV concentric hypertrophy in severely affected dogs. The most common finding in severely affected dogs is enlargement of the aortic root or widening of the mediastinum due to post-stenotic dilation of the aorta.
Two dimensional and M-mode echocardiographic findings are often normal in mild to moderately affected individuals. Left ventricular hypertrophy is usually readily apparent only in moderately to severely affected dogs. In these cases, the M-mode echocardiogram demonstrates increased diastolic septal and LV free wall thicknesses (LV concentric hypertrophy) and a normal LV shortening fraction. The narrowed subvalvular region can sometimes be identified while sweeping the M-mode transducer from the LV to the level of the proximal aorta (Ao) level, but 2D evaluation is more accurate for this purpose. Other findings may include post-stenotic dilatation of the ascending aorta, secondary thickening of the aortic valve cusps, and mid-systolic partial closure of the aortic valve cusps. In some cases of SAS, the mitral valve E-F slope decreases due to reduced compliance of the hypertrophied left ventricle. This should not be misinterpreted as mitral stenosis. Overall, M-mode examination alone is not very reliable for identification or confirmation of congenital SAS except in severe cases.
In cases of moderate to severe SAS, the subvalvular lesion can usually be identified by an experienced echocardiographer. The secondary concentric hypertrophy is more readily identified. In mild cases, the obstruction may be difficult to distinguish except as minor irregularities in the LV outflow tract. The obstruction appears as a narrowing between the ventricular septum and the base of the anterior mitral valve leaflet, just proximal to the aortic valve on the right parasternal or left cranial long-axis views. It usually appears as a discrete membranous or fibromuscular ridge. Rarely it is as a longer, tunnel-type obstruction. The subvalvular fibrous narrowing may also be identified in the right short-axis view as a circular or oval ring in the outflow tract, below the aortic valve. A recent study has demonstrated that the ratio of the cross-sectional area of the fibrous ring to the proximal aortic cross sectional-area from this view may be used to classify the severity of the lesion when Doppler echocardiography or cardiac catheterization are not available. The areas of the fibrous ring and proximal Ao were determined planimetrically by tracing the outline of each structure from the right short axis 2D views. In this study, a logarithmic relationship between the fibrous ring/Ao ratio and the Doppler pressure gradient was obtained (R value = 0.88). When the ratio is divided into three ranges (>0.5 = mild, 0.3-0.5 = moderate, and <0.3 = severe) it correctly predicts the severity of SAS (as determined by Doppler echocardiography) 84% of the time.
The aortic valve often appears mildly thickened from the continuous trauma associated with the stenotic jet. Areas of ischemic fibrosis appear as hyperechoic areas in the LV papillary muscles or subendocardium. In many cases, post-stenotic dilation of the ascending aorta is recognized, but this can be slight in dogs less than six months of age. It may be identified in the right long-axis view, but is usually identified best in the left cranial long-axis view. It is common to observe mildly thickened mitral valve leaflets with diminished diastolic motion, but these valves are usually functionally competent. The left atrium is normal or mildly dilated in most dogs with SAS and normal mitral valve function. Cats with aortic stenosis display similar echocardiographic findings.
As with pulmonic stenosis, Doppler echocardiography is useful for determining the location of the stenosis and its severity, as well as accompanying complications. It is critical for the diagnosis of mild SAS in animals without clear abnormalities on the 2D examination. Color flow Doppler examination demonstrates a broad systolic jet in the proximal aorta and diastolic aortic valve regurgitation in the LV outflow tract. O'Grady found spectral Doppler evidence of mild aortic regurgitation in 87% of 53 dogs with SAS. Our experience, using color Doppler imaging, is that mild aortic valve regurgitation is present in almost every dog with SAS, and that this may be one of the most sensitive indicators of SAS in dogs with the mildest defects. It is rare to find aortic regurgitation in normal dogs or dogs with other cardiac abnormalities except for those with a ventricular septal defect or bacterial endocarditis of the aortic valve. Pulsed-wave Doppler studies in the LV and aorta typically show a normal contour and velocity to the tracing in the LVOT below the lesion and spectral broadening and a step-up in velocity across the obstruction and in the ascending aorta. Continuous wave Doppler examination of the LVOT and proximal aorta can be performed from the left apical position, a subcostal position, and a thoracic inlet (suprasternal) position. Lehmkuhl & Bonagura recently studied 12 dogs with SAS and reported that highest peak velocities were obtained from the subcostal position in 10 dogs (83%), the suprasternal position in 1 dog (8%), and the apical position in 1 dog (8%). The typical CW tracing shows an increased systolic velocity toward the aorta and a high velocity holodiastolic signal toward the left ventricle. The modified Bernoulli equation is used to calculate the peak systolic pressure gradient. This is used, in combination with other clinical and echocardiographic findings, to estimate the severity of the lesion. Controversy exists as to what peak velocity measured in the LVOT and Ao is considered diagnostic for SAS. Most cardiologists agree that any velocity greater than 2.0 m/sec is supportive of the diagnosis. However, most normal dogs have peak velocities in this region less than 1.5 m/sec (usually less than 1.2 m/sec), such that there is a range of velocities between 1.5 and 2.0 m/sec, that in isolation, should not be used as diagnostic criteria for SAS. It is most appropriate to combine the peak velocity measurement with other echocardiographic findings, such as an increase in velocity between the LVOT and the aorta, the development of turbulence at the subaortic region, or the visual appearance of the lesion, and other clinical data to accept or refute the diagnosis. In general, dogs with a calculated pressure gradient less than 40 mmHg are considered to have mild SAS, dogs with gradients greater than 80-90 mmHg are considered to have severe stenosis and those in between are regarded as moderately affected. One must appreciate, that these are arbitrary categorizations that may not be appropriate in all cases. Doppler findings are similar in dogs with dynamic lesions except the peak velocity may be quite variable and the continuous-wave Doppler tracing usually displays an increasing rate of acceleration (the velocity contour is concave to the left) and a peak systolic gradient in late systole, a pattern that is not seen in patients with a fixed obstruction (see Figure 4).
NATURAL HISTORY AND PROGNOSIS
Most dogs with severe SAS die suddenly or have symptoms that degrade their quality of life. Sudden death usually occurs in the first 3 years of life mainly, but not exclusively, in dogs with severe obstructions (gradient >80 mmHg). Up to 70% of severely affected dogs die suddenly during this time. Infective endocarditis and left heart failure are uncommon in dogs and tend to occur later in life. These complications usually occur in dogs with mild to moderate obstructions, probably because these dogs live long enough to develop secondary complications. Left heart failure is uncommon in the absence of additional congenital defects or infective endocarditis. Dogs born with moderate to severe mitral valve dysplasia that develop moderate to severe SAS usually develop severe heart failure between three and six months of age. Their prognosis is often poor. Dogs with a mild obstruction usually live a normal life expectancy and only rarely exhibit clinical signs. The prognosis for long-term survival in dogs with untreated mild or moderate SAS is favorable while the prognosis for dogs with severe SAS is generally poor.
Therapy is generally directed at preventing sudden death and/or reducing exercise intolerance or syncopal events. Therapy is usually unnecessary in mildly affected individuals and the efficacy of treatment is unknown in patients with moderate to severe aortic stenosis.
Although no scientific studies have documented efficacy, most veterinary cardiologists prescribe a beta-adrenergic blocking agent for dogs with a history of syncope or documented exercise intolerance, for dogs with frequent ventricular arrhythmias or ST segment depression, and for dogs with a pressure gradient in the moderate to severe range. Beta-adrenergic blocking agents are utilized primarily in an attempt to prevent sudden death. Beta blockers prevent the arrhythmic effects of catecholamine surges on diseased myocardium. They also reduce myocardial oxygen demand and increase coronary perfusion by decreasing heart rate and contractility. The latter effects may prevent further myocardial ischemia associated with LV hypertrophy, increased systolic wall stress, and abnormal coronary flow dynamics, and therefore may reduce the incidence of lethal ventricular arrhythmias. Although probably beneficial in some patients, we have documented others that have died suddenly or have continued to have clinical signs while receiving beta-adrenergic agents. Propranolol (1 to 2 mg/kg q8h) and atenolol (6.25 to 50 mg q12h) are the most commonly prescribed beta adrenergic blocking drugs. The dose of both drugs must be increased as dogs grow. Beta receptor density in the myocardium increases during the administration of these drugs. Sudden cessation of beta blocker administration results in the sudden unmasking of an increased number of beta receptors. This can result in an exacerbation of a ventricular arrhythmia and can lead to sudden death.
Prophylactic antibiotics are advocated in humans with any degree of subaortic stenosis during potential bacteremic episodes (dental procedures, general surgery, severe skin disease) to reduce the risk of bacterial endocarditis. As such, some veterinary cardiologists recommend the same precautions in dogs. The benefits of this approach are unproven.
©Mark D. Kittleson, D.V.M., Ph.D. All rights reserved.