Tricuspid valve dysplasia - what’s in a diagnose?
Student
Study
Supervisor
Date
Eveline J. Snellen van Vollenhoven, BSc.
Veterinary medicine of companion animals, Utrecht University
Ms. drs. M. den Toom
17-11-2014
Retrospective study of prevalence, clinical presentation and outcome in dogs
diagnosed with tricuspid valve dysplasia at the university clinic for companion
animals in the Netherlands.
E.J. Snellen van Vollenhoven, BSc
Abstract
Tricuspid valve dysplasia (TVD) is a congenital malformation of the right atrioventricular valves. This
disease is known to cause right sided congestive heart failure in dogs. Clinical signs of symptomatic
patients include exercise intolerance, syncope, dyspnea and ascites. Because of a low prevalence,
there is only limited information available about the clinical presentation and prognostic factors in
dogs with TVD. Prognostic factors mentioned in literature are the degree of tricuspid regurgitation
and associated cardiac enlargement, and the age of onset of cardiac complaints.1 However, these
factors are based on personal experiences and not on results of scientific studies.
In this study, we aim to gain more knowledge about the prevalence, clinical presentation and
prognostic factors. Between January 2002 en September 2014, 24 patients were diagnosed with TVD
in the university clinic for companion animals in Utrecht, The Netherlands, which equals 6.1% off our
total population of patients which congenital cardiac diseases.
This study showed a significant difference in survival time between the patients that became
symptomatic within 1 year of age and the patients that developed clinical signs after their first year
(p=0.006). Literature suggests no existing relationship between the intensity of the murmur over the
tricuspid valve and the prognosis. In the groups of patients that presented with a louder murmur
compared to the group with a softer murmur, we found a higher percentage of symptomatic patients
within one year of age (33.3% vs. 44.4%). However, no significance was proven.
Echocardiographic findings that are seen in TVD are insufficiency of the tricuspid valve, eccentric
hypertrophy of the right ventricle and right atrium dilation. The median follow-up time of a patient
with milder cardiac changes on echocardiogram, is higher than in patients with more severe changes.
These results are found in both the entire cohort, as well as in the group of patients that died during
follow-up (survival time). Also, the mean age at death in symptomatic patients is higher in this first
group, compared to the second group (51.5 months versus 28.3 months). Furthermore, patients with
more severe changes on echocardiogram developed cardiac complaints at a younger age, when
compared to patients with fewer changes on echocardiogram.
Introduction
TVD is a congenital malformation of, as the name suggests, the right atrioventricular valve.
Associated cardiac anomalies are observed. One study showed that in 26% of the patients with a
malformation on the tricuspid valves, another malformation was diagnosed simultaneously. These
malformations included (among others) patent ductus arteriosus, pulmonic stenosis, and subaortic
stenosis.2
TVD is a very rare disease, with a prevalence ranging from 3.1%2 up to 7.4% in academic veterinary
hospitals.3 Although not all studies underline this2, male dogs seem to be predisposed.1 The Labrador
Retriever, Golden Retriever, Great Pyrenees, Great Dane, German Shepherd, OId English Sheepdog
and Weimaraner are known to be predisposed.4
Ebstein anomaly is a specific form of a tricuspid malformation. In this case the tricuspid valves are
displaced more towards the apex of the heart; ‘right ventricular atrialization’. Since canine tricuspid
malformations come in many varieties of which only some have the specific features of Ebstein
anomaly, the term TVD is preferred over Ebstein anomaly in veterinary literature.5 In Labrador
Retrievers, Ebstein anomaly was found to be inherited autosomal dominantly which maps to
chromosome 9.6
Patients with TVD are often asymptomatic at the time of diagnosis. Physical examination reveals a
holosystolic murmur with the point of maximal intensity over the right atrioventricular valve.
Sometimes, a systolic click can be heard. According to literature, the intensity of the murmur cannot
be correlated with the severity of the dysplasia.1 Clinical signs associated with TVD are exercise
intolerance, syncope, dyspnea and/or ascites due to right sided congestive heart failure. Heart and
lung sounds may be diminished because of pleural effusion.7
The most accurate way of diagnosing TVD, is by performing an echocardiogram, Here, an enlarged
right atrium and eccentric hypertrophy of the right ventricle can be found as a result of the tricuspid
regurgitation during systole.8 Furthermore, tricuspid valves may appear thickened , enlarged or
adhered to the interventricular septum. The left side of the heart may appear to be decreased in
size.5 The chordae tendinae are mostly shortened or even absent, and the leaflets of the
atrioventricular valve may be misplaced (e.g. Ebstein’s anomaly) or thickened.9 Electrocardiographic
findings in dogs with TVD mainly consist of atrial tachycardias and arrhythmias, and splintered QRScomplexes. 10, 11
If TVD is diagnosed at early onset, surgical repair of the tricuspid valve can be a option.
In a study of 12 dogs that had received either a bovine or porcine valve, 2 dogs died because of
cardiac arrests, and 4 dogs were euthanized because of serious post-surgical complications.
Other dogs had a survival rate between 1 month and 66 months after surgery. Complications of the
surgery included atrial flutter, inflammatory pannus, thrombosis and endocarditis.12
Medical treatment of symptomatic dogs with TVD primarily focuses on reducing the preload and on
controlling the heart rate in the case of arrhythmias.1 Preload of the heart can be manipulated by
using diuretics (furosemide) and ACE inhibitors (benazepril). More on, the positive inotropic and
vasodilating effect of pimobendan can affect the development of congestive heart failure. Low-salt
diets to reduce water retention are also advised.1 Controlling of the heart rate can be accomplished
by administering digoxin, calcium channel blockers, and beta-blockers.1
The prognosis varies greatly, based on the degree of tricuspid regurgitation and associated cardiac
enlargement. As previously mentioned, the intensity of the murmur is not per definition correlated
with the prognosis. Animals with mild TVD and mild cardiomegaly often remain asymptomatic and
may have a normal life span. Dogs with signs of congestive heart failure before 1 year of age usually
have a poor prognosis.1
The aims of this study are 1) to gain more knowledge about the prevalence of TVD in a referral
veterinary hospital in the Netherlands, 2) to determine clinical presentation of the patients and
3) to evaluate prognostic factors.
Materials and methods
All dogs that were diagnosed with TVD between January 2002 and September 2014 at the university
clinic for companion animals in Utrecht, the Netherlands, were selected from our digital database
Vetware. Diagnostics had previously taken place by a cardiologist, or a resident in cardiology
supervised by the cardiologist. All animals underwent physical examination and an echocardiogram
to diagnose TVD.
From the database, 28 patients were extracted by searching on congenital heart disorders – tricuspid
valve dysplasia and searching on congenital heart disorders - Ebstein.
Out of 28, 4 were excluded because the diagnosis was uncertain. For this retrospective review the
owners, and in some cases the referring veterinarians, were approached. After consent of the
owners, the patients were included in this research. In some cases, the dogs unfortunately were
already in congestive heart failure when presented at the clinic. The dogs that were euthanized
immediately or shortly after were still included.
In two cases, we were unable to reach the owner, yet from one of these dogs we were able to
retrieve the data via the referring veterinarian. Therefore, only one dog got lost in follow-up
immediately after diagnosis.
Information that was used in our research included the breed and age of the dogs, preexisting
physical conditions of the patient, physical complaints which suggested a cardiogenic problem
(coughing, exercise intolerance, syncope, etc.) and history of medications. Furthermore, intensity of
the murmur had previously been determined by the cardiologist or the cardiologic resident.
From echocardiography, the following parameters were used for the analyses: 1) severity of
insufficiency of the tricuspid valve, 2) presence and severity of eccentric hypertrophy of the right
ventricle and 3) presence and severity of dilation of the right atrium. All of these parameters were
subjectively defined as either mild, moderate or severe. The owners, and in some cases the referring
veterinarians too, were given a questionnaire which provided us with information about the lifespan,
cause of death, use of medication, and development of clinical signs of congestive heart failure.
For analysis of the data that was collected, all data was entered in the statistics program SPSS.
Kaplan Meier and life tables were used for survival analyses.
For all patients, the follow-up time and/or survival time was determined in months, starting the day
of diagnosis.
Results
In total 389 dogs were diagnosed with congenital heart defects between January 2002 and
September 2014. Out of these dogs, 24 suffered from TVD (6.1%) (table 1). Since not all data from
the patients was complete, not every patient could be used in every single analysis.
From the 24 included dogs, 12 were male, 12 female. 11 dogs were Labrador retrievers, the other
breeds included 2 Golden retrievers, 2 Bordeaux dogs, 1 French Bulldog, 1 Old English Sheepdog, 1
Great Dane, 1 Weimaraner, 1 Clumber Spaniel, 1 Rottweiler, 1 Leonberger, 1 Dachshund and 1
crossbred (Flatcoated Retriever x Labrador Retriever) (table 2).
Survival time and follow-up time
For all patients, the follow-up time was measured in months, starting the day of diagnosing TVD at
the faculty of veterinary medicine in Utrecht (figure 1). The follow-up time of the complete cohort
therefore includes patients that died during follow-up, and patients that were censored because they
were still alive at time of the questionnaire. From the patients that died during the period of followup, the survival time in months was written down.
Figure 1. Survival curve. Survival time post diagnosis in months. Patients that were still alive at the end of
follow-up are censored.
Among all patients, the median follow-up was 9.5 months, ranging from 0,00 (euthanized
immediately after diagnosis) up to 108 months (table 2). As can be seen in figure 1 and table 2, 7/24
patients died in the first 2 months after initial diagnose. The last dog was lost in follow-up after 108
months. At that moment, he was still alive and therefore censored in the plot.
12 dogs died during the follow-up time of this study. Ten out of twelve patients were euthanized due
to cardiac failure, 1 dog died while under general anesthesia during a surgery for gastric dilation
volvulus, yet asymptomatic in light of his cardiac condition. 1 dog was euthanized after 183 months
(75 months post diagnosis) for arthrosis, being asymptomatic as well.
The median survival time among the 10 patients that died because of cardiac failure was 2 months,
with 34 months being the maximum survival time after diagnosis.
Among the asymptomatic patients, the median follow-up time was 24 months.
Effect of the intensity of the murmur
To investigate a possible correlation between the intensity of the murmur on the tricuspid valve and
the survival time, two groups were formed. All patients were divided into these groups depending on
their murmur, being 1) either no murmur or a murmur with an intensity between 1 and 3 out of 6 or
2) a murmur set at 4 or higher.
Within these groups, the median survival time was reviewed. For the patient that had no detectable
murmur, we made the assumption that based on the findings on echocardiogram, there must have
been a murmur. It can probably be missed due to panting or heavily breathing. It is reasonable to
believe it has been a soft murmur, and therefore this dog was placed in the lower murmur category.
As can be seen in table 3, there is a big difference in survival time among the different murmur
categories. Because there is only a small amount of patients in each group and there is a big spread
among them, the median survival time is more interesting than the mean survival time. In the
evaluation of the total group, the group with a softer murmur had a higher median survival time,
than the group with a louder murmur (18.00 vs. 6.00). Since the follow-up time included patients
that were still alive at the time of study, this cannot be used for analysis on survival time.
The median asymptomatic period was longer in animals presenting with a softer murmur compared
to those with a louder murmur (24 months vs. 10 months). No significance could be proven,
unfortunately.
During follow up, 10 patients were euthanized because of cardiac failure. (table 2). In this group with
an actual known survival time, the median survival time of patients with a softer murmur is higher
when compared to the louder murmur category . Unfortunately, this last ‘group’ only consisted of 1
patient, and could thus not be proven to be significant. This higher categorized murmur patient also
had a younger age at time of death, when compared to the mean of the other group.
The groups that presented with a louder murmur, had a higher percentage of symptomatic patients
within one year of age. Since the numbers are too small, no statistics could prove any significance.
Effect of severity of echocardiographic abnormalities
As described, all echocardiograms findings as written down by cardiologist were marked as either
mild, moderate or severe. For this part of the study, a calculation was made whereby 1 point was
accredited for a mild change, 2 for moderate changes and 3 points for severe changes. The sum of
the three parameters that were used (table 2) defined the group in which the patient was placed
(table 4).
The median follow-up time of a patient with milder cardiac changes on echocardiogram, is higher
when compared to the group of patients with more severe changes (table 4). These results are found
in both the entire cohort, as well as in the group of patients that died during follow-up. In the group
that died during follow-up, these number are a twentyfold higher. Also, the mean age at death
among the symptomatic patients with more severe changes (28.33 months) is shorter, when
compared to the two patients with a lower score (51.50 months).
As seen in table 4, interestingly, patients with more severe changes on echocardiogram were more
likely to have developed cardiac complaints at a younger age, when compared to patients with fewer
changes on echocardiogram. Again, this is only a very small group of patients (n=2) so no statistics
could be used.
One patient with a high score from 7 out of 9 on echocardiographic changes, never developed any
complaints in his 183 months of life.
Symptomatic patients
Of the 18 patients that developed complaints during the time of study, the mean and median age of
onset of clinical complaints was calculated (table 5). The youngest age of onset was 4 months, the
eldest developed signs of cardiac failure at 65 months. The median was calculated at 11.50 months,
thus 50 percent of the patients that developed complaints, did so in the first year after birth.
Among the 10 symptomatic patients that died during follow up, 5 became symptomatic within 1 year
of age (table 6). The mean age at death among this 10 patients was 54.46 months, the mean age at
death among the deceased patients that became symptomatic within the first year of their life was
9.84 months. We have found a significant difference, between these two groups (p=0.006, twosampled t-test), thus if patients develop clinical signs within their first year of life, they die younger.
Cardiac drugs
Out of the 15 patients that developed clinical signs during the time of follow-up, 8 patients received
cardiac drugs. These drugs included multiple ACE-inhibitors, multiple different diuretics, digoxine, a
β1 receptor antagonist, calcium sensitizer and a calcium channel blocker. 7/8 dogs were euthanized
after an unknown period of receiving medication. The patient that was still on cardiac medication
during follow-up, had only a short follow-up period after diagnosis (2 months).
Discussion
6.1% off the patients with a congenital disorder, was diagnosed with TVD. Off these dogs, 50% was
male and 45.8% was a Labrador retriever. These findings are very similar to what has been found in
earlier studies.2-4 Other breeds which have been described with a higher prevalence of TVD , were
also found in our database.13 25 percent of our patients had more than one cardiac congenital
abnormality at time of diagnosing. Oliveira et al. found the combination of TVD with another
congenital heart defect in a prevalence of 26%.2 Our cohort can be seen as a representative group of
patients.
For this study we have used multiple parameters to compare with multiple outcomes. One of the
outcomes we used was defined as age of onset of complaints. A hazard in determining the age of
onset might be the fact that the owners were subjectively asked to determine this age. The best way
to define if a patient is symptomatic or not, would be to evaluate him in a veterinary clinic.
The small amount of patients included in this study, is most definitely the greatest hazard. Therefore,
hardly any statistics could be used to determine significance in our findings.
Since follow-up time includes patients that are still alive as well as patients that died in time of the
study, the follow-up time is not a good parameter for evaluating the effect of a more intense murmur
on survival time. The group of patients with a louder murmur that died during follow-up, only
consisted of 2 patients and therefore no conclusions can be drawn from this data.
We have found a very great variety in age of onset among our patients, which makes interpretation
very challenging. For example, the mean age of onset of clinical complaints in the group with a
murmur ranging from 0 to 3, is higher than in the higher categorized animals. This would suggest that
patients with a louder murmur, would develop clinical sings earlier on. Nevertheless, 4 out of 9
patients in that category didn’t develop any clinical signs at all. For example, one of the patients in
this group was diagnosed with a murmur from 5 out of 6 at 28 months of age, and this dog was
(according to the owners) still asymptomatic 24 months after diagnostics had taken place. According
to earlier literature, there is no correlation between the intensity of the murmur and severity of the
cardiac disease in dogs.1
The mean and median follow-up time of a patient with milder cardiac changes on echocardiogram,
are higher when compared to the other group (table 4). These findings are similar in both the entire
cohort, as in the group of patients that died during follow-up. It is interesting to see, that the more
severely affected animals also have a younger age at onset of complaints. Patients with more cardiac
changes on echocardiogram had a shorter survival time. As changes in the heart are a direct result of
a cardiac dysfunction, it is likely to assume that more cardiac changes equal a worse prognosis. This is
in line with what we expected and earlier found outcomes.1
Fifty percent of our symptomatic patients, developed cardiac failure within the 4th month up to the
first year of their life. The other 8 symptomatic patients developed clinical sings from 15 months, up
to 65 months of age. These data and also previous literature suggest, that the chance of developing
clinical signs, decreases greatly after the first year of age.1 Animals that developed symptoms within
the first year after birth, have a significant shorter lifespan than animals that become symptomatic at
a later age. This relationship between the age of onset of clinical signs in light of prognosis, has also
been described previously.1
Determining the intensity of the murmur, as well as the severity of abnormalities on
echocardiogram, can be quite subjective. All of our used parameters were determined by either a
cardiologist, or an older resident in cardiology while using standard guidelines. Therefore, we believe
that we were able to apply these parameters as objective as possible.
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