Feline Heartworm Disease
Pathophysiology of Heartworm Associated Respiratory Distress (HARD) in Cats
The pathophysiology of feline heartworm disease is significantly different from that of dogs in that a great deal of the inflammatory condition and clinical signs stem from immature larvae in cats. While cats are significantly more "resistant" to heartworm infection than dogs, meaning that fewer infective larva will survive to adulthood, they seem to be much more susceptible to clinical disease on a "per parasite" basis. Consequently, serious disease may result in a cat that receives a smaller number of L3 larvae from the mosquito as compared with the dog.
Following infection with L3 larvae, a 3-4 mo migration occurs in the subcutaneous tissues while the larvae grow and molt twice. L5 larvae technically are young adults as they will not molt again; they enter the venous vasculature and are transported passively with the blood to the right heart. They are too large to pass the capillary bed of the pulmonary circulation and so are retained there. Cats are resistant to infection in that most infective larvae die before reaching adulthood. While there is a very high initial mortality rate as L5 larvae reach the lung, survivors may live for 2-3 years in the cat and attain the size of 4-5 inches in length.
One of the dramatic differences between dogs and cats is that the latter are extremely sensitive to the inflammatory reaction caused by larvae whereas the principal pathology in dogs is caused by interaction with the adult worms. Unlike dogs, cats have pulmonary intravascular macrophage (PIM) that engulf parasite fragments and contribute to the inflammatory reaction, releasing cytokines and promoting a proliferative response in the arteries and small airways of the lung. Arterial walls become thickened, contributing to increased vascular resistance. The inflammatory response leads to intercellular gaps and leakage of inflammatory fluid into the surrounding tissue. Intravascular thrombosis may occur and the inflammatory reaction may cause impairment of pulmonary function and intense clinical signs.
Clinical signs of HARD and Heartworm Disease in Cats
The initial inflammatory cycle occurs when immature parasites (L5) reach the lungs, 3-4 months post infection. Clinical signs of HARD, including severe respiratory distress and sudden death, can occur prior to seroconversion of any currently available antigen or antibody test. Recurrence or exacerbation of clinical signs may result when adult heartworms die, resulting in cough, respiratory distress (clinical signs of asthma), with each inflammatory cycle. Cataclysmic clinical signs are most often associated with parasite death.
Clinical signs are often vague and not localized to the cardiorespiratory system at all. One of the most commonly reported clinical sign in the cat is vomiting; this may be the only clinical sign. Clinicians won't diagnose this condition without a proactive inclusion of heartworm infection in the differential list for cats without localizing clinical signs. If it "ain't doin' right", it might be heartworm, just like it might be FeLV, FIV, CRD, etc. Here is a breakdown of clinical signs most typically noted in the cat.
- Frequent emesis-16%
- Sudden death-10%
- Central nervous system-4%
From Atkins, C. Feline Heartworm Disease. In Ettinger & Feldman. Textbook of Veterinary Internal Medicine, 6th edition. 2005 Elsevier
Cats are much more prone to aberrant infections than dogs. These are infections where adult parasites end up somewhere other than the pulmonary circulation. Notable locations include systemic arteries, the central nervous system, and the eye. Hence the possibility for "incidental" clinical signs in the above, i.e. a wide range of nonspecific abnormalities that depend on the location of the parasites.
Prevalence of Feline Heartworm Disease in the Northeast
One of the biggest questions we all have it is: What is the prevalence of heartworm disease in Vermont in cats, or in dogs for that matter? We know that the climate in Vermont is not particularly conducive to propagation of heartworm disease since maturation of Dirofilaria larvae (L1 - L3 stages) in the mosquito vectors depends on warm ambient temperatures for a minimum of 10 - 14 days. Prevention of the disease has never been easier which may contribute to the low prevalence in the reservoir canine population, thereby helping to minimize feline infections. Nevertheless, the canine prevalence is not negligible as suggested by official data from the American Heartworm Society (below). There is even a suggestion that the Lake Champlain area has an increased local prevalence.
Prevalence of heartworm disease in dogs, 2007: From the American Heartworm Society
Available reports of feline prevalence refer to an article in the Proceedings of the American Heartworm Society where no cases were reported for Vermont (Ryan WG, Newcomb KM. Prevalence of feline heartworm disease - a global review. In: Soll MD, Knight DH, eds. Proc Heartworm Symposium '95. American Heartworm Society, Batavia, IL. 1996;79-86.) However, the methods of this determination must be considered carefully. The paper reported only on heartworms seen at necropsies performed at animal shelters. It's clear that you won't find any if you don't look, and that's about all we can infer from the report -- nobody looked. A high "index of suspicion" is critical for diagnosing feline dirofilariasis regardless of geographic location or the method by which infection was determined. I daresay it's probable that many heartworm positive feline cases would be missed on necropsy examination since 1) it's unusual for parasites to reach adulthood in the cat, 2) adult parasites typically die and fragment so that one would not necessarily any, and 3) small parasite fragments are located in the distal pulmonary arteries, i.e. are relatively inaccessible. It takes a diligent, experienced pathologist who's willing to dice the lung out to these locations to have a chance of finding evidence of infection in the form of fragmented or whole parasites.
The same paper above reported a prevalence of 0 - 8% in New Hampshire (necropsy evaluation). Why the immense variation? Well, one year there were no parasites found. The next year there were 5 cases in 66 cats necropsied!! This raises the issue that some years may be particularly conducive to propagation of the disease, e.g. depending on how consistently warm the summer months are in a given year.
From Atkins, C. Feline Heartworm Disease. In Ettinger & Feldman. Textbook of Veterinary Internal Medicine, 6th edition. 2005 Elsevier. Original data from Stackhouse LL, Clough E. Clinical report: five cases of feline dirofilariasis. VM /SAC 1972;67:1309-10).
If the true prevalence of feline heartworm disease in Vermont were anything like 8%, then we would be seeing one heck of a lot of heartworm disease (or it would be seeing us). My perspective on this condition is different from yours. I (hopefully) get the cases that are suspected of the disease funneled in for cardiac evaluation, so I actually see a few of these every year (none confirmed in Vermont yet). So if your perspective is that you hardly ever see the disease, mine is "Oh no, not again!" Affected cats can be very sick and there are no good treatment options. Prednisone seems to help them feel better and improve clinical disease, but the presence of adult heartworms means you never know when the cat might experience clinical signs that may include severe dyspnea or sudden death. After you've dealt with a few of these cases, and the distress that both cats and owners go through, you wonder why they aren't all on preventative. How high does the prevalence need to be before you start recommending heartworm preventative for cats? I believe that the answer to this question is simpler than you might think. If you believe that Vermont dogs should be on heartworm preventative, then you believe that the cats should be also! Necropsy surveys of shelter cats have placed the prevalence of adult heartworm infections at 5 to 15% of the rate in unprotected dogs in a given area. With most cats unprotected, we could very well have a higher incidence in the cats than the dogs. While mosquito species do appear to prefer canine blood, cats are being attacked by the same population of insects!
Serologic Testing for Feline Heartworm Disease
We have two kinds of serologic tests used for feline heartworm disease: antigen tests and antibody tests. Antigen tests detect somatic antigen from the female reproductive tract of adult heartworms. Consequently this test will be positive if there are a sufficient number of mature female adults that are secreting antigen into the circulation. Manufacturers of heartworm antigen tests are now claiming sensitivity down to a minimum of a single female adult parasite. I think it is advisable to discount this claim somewhat and not rule out the possibility of a small number of female adults in the presence of a negative test, i.e. false negatives may still occur. I remember a case where the 3Dx test run by a practitioner was positive, and heartworms were visible on echo, but the sample sent off to IDEXX for confirmation was negative - twice! A common scenario that will increase the sensitivity of the test is to have a female adult die. This releases antigen into the circulation and results in a much more reliable test. If you suspect heartworm disease in a dog or cat that's coming up negative, recheck the test a week or two after an exacerbation of clinical signs (which is often caused by heartworm death).
There are obvious problems with the antigen test for cats. 1) Because of the small number of parasites involved in a typical infection (e.g. 1-3), it's statistically likely that male unisex infections will occur resulting in a false negative. Necropsy data from animal shelters indicated that 50-70% of cats had 1 or more female adults; that's the best sensitivity you can hope for with this test. 2) It's common for the cat's immune system to destroy the parasites before (or after) they reach adulthood so that the test is a poor indication of whether the cat was infected. 3) Clinical disease in cats is not dependent upon the presence of adult heartworms as it is typically in dogs. Consequently the antigen test may be a very poor test if you are trying to relate clinical disease to heartworm infection. Nevertheless, the presence of a positive antigen test in a cat experiencing appropriate clinical signs is a strong indication of heartworm disease.
Feline antibody tests detect antibody generated by the host against either male or female larvae; this occurs as early as 2 months post-infection. However host defenses often rid the cat of the infection prior to maturation of the parasites. Hence feline antibody tests have the potential to indicate whether an infection occurred but do not indicate that parasites are present, either immature forms or adults. Furthermore, these tests may be much less sensitive than hoped for. While initial laboratory testing suggested 98% sensitivity, field sensitivity ranged from 32-89% in cats with adult parasites present as determined from necropsy examinations performed at animal shelters. A negative antibody test does not rule out heartworm disease in a cat! It seems that the test is more likely to be positive if there are clinical signs.
Here's the bottom line (in my opinion):
- Neither the antigen or antibody test is an adequate screening test for feline heartworm disease. Neither is sufficiently sensitive.
- Negative antigen and/or antibody tests do not rule out clinical disease from heartworm in a cat.
- A repeatably positive antigen test is indicative of adult females, alive or recently dead. Clinical disease from adults is likely.
- A repeatably positive antibody test is compatible with past or current heartworm infection. A cat with a positive test need not be experiencing any clinical signs or pathology. However the possibility that clinical signs are related to infection must be carefully weighed.
We've recently had some e-mail discussion about IDEXX bundling their feline antibody test with other test products. This might be valuable from an epidemiological standpoint if IDEXX were to make the results known to area veterinarians. We know from the above that positive test results would give some indication of the prevalence of exposure in the test population; the prevalence might be underestimated by a factor of 2-3 by this method. Cats with a positive test and clinical signs consistent with heartworm disease (just about any clinical signs) would be candidates for further investigation. However, we would also expect that many cats testing positive would have no clinical disease. Most experts agree: It takes a high index of suspicion and a multi-pronged approach to diagnose FHD.
Imagine yourself in the position of working up a feline patient with a nebulopathy (ADR). You may have already run a CBC and chemistry profile on the cat that presents for nonspecific reasons. These tests are unlikely to give you a hint that heartworm disease is present. If respiratory signs are present, however, thoracic radiography may be the first specific test you perform on a cat that actually has the disease. You already know what those radiographs may look like, and that's because you've already seen a cat with asthma. The radiographs may look just the same! Findings suggestive of heartworm disease include:
- Enlarged caudal pulmonary arteries with ill-defined margins
- Focal or diffuse infiltrates; interstitial, bronchointerstitial, or alveolar
- Perivascular density
- Pulmonary hyperinflation
Enlargement of the main pulmonary arteries may be a relatively specific finding suggesting feline heartworm disease, plus/minus tortuosity just as seen in the dog; this is only about 50% sensitive for adult infection however. Pulmonary angiography actually is a sensitive and specific test for adult parasites which appeared as linear filling defects within the pulmonary arteries. We don't like to be that invasive unnecessarily.
Example radiographs from a cat with feline heartworm disease. Click here for another example.
The occurrence of dirofilariasis in a cat is unusual enough that it takes a great deal of suspicion and expertise to make this diagnosis echocardiographically. It's possible for there to be only a single frame in an entire study that depicts a parasite definitively. Parasites must be differentiated from artifact and so there is the potential both for false negative (frequently due to inaccessibility of parasites) and false positive results (due to overinterpretation of images). Nevertheless sensitivity of echocardiography for making this diagnosis in the cat has been estimated at about 80%. In my view, variation of parasite size/maturity in the cat complicates the image interpretations. Clinical signs may be the result of highly immature worms and these may be quite different in appearance from expectations derived from seeing parasites in dogs. Nevertheless, it is my feeling that all cats (and most cysts dogs) suspected of heartworm disease should be examined echocardiographically.
It's typical that a diagnosis of heartworm disease has not been established by the time we perform an echo. You're still trying to find out what the problem is and echocardiography is a pretty good test for heartworm disease! We are not only looking for parasites, but a reason for cardio-respiratory signs in general. If the patient does have heartworm disease (e.g. visualized parasites), then we also need to evaluate the severity of the condition and the echo is helpful for that as well. We can establish some idea of parasite burden and location (important if we're going to try to remove them) as well as their effect upon the cardiovascular system including pulmonary hypertension, right ventricular dilation and/or hypertrophy, and tricuspid regurgitation. Abdominal and/or pleural effusion may occur secondary to heartworm disease, readily determined by echocardiography or radiography.
Echocardiographic image from a cat with extreme Dirofilaria infestation. The left-hand side of the image depicts the right ventricle near the top of the image and the right atrium towards the bottom. The right atrium contains many adult parasites which appear as "double track" echogenic structures (sagittal of parasite) or "doughnuts" (transverse). This constitutes a rare case of vena cava syndrome in a cat. A video image of this heart depicts the parasite mass moving between the right ventricle and right atrium with each cardiac cycle. Typical feline infestations include 1-3 parasites which may be very difficult to spot.