Heartworm disease is an elusive diagnosis in feline patients. As such, a thorough understanding of the pathogenesis of feline heartworm disease (FHWD) is needed to interpret test results. How heartworm disease differs in cats and dogs Cats become infected with heartworms in much the same way as dogs. However, while cats are susceptible hosts, they differ significantly from dogs in the number of infective heartworm larvae that survive to adulthood. Once the infective third-stage larvae (L3) enter the host animal, they molt to fourth-stage larvae (L4), migrate through tissues, molt a second time to an immature worm (fifth stage), and then penetrate a peripheral vein. They are carried by the circulation to and through the heart to the caudal pulmonary arteries where they continue to develop. By 100 days postinfection, these immature worms are 2 in. long. The initial pulmonary artery pathology in the cat is similar to the dog in that there is muscular hypertrophy, villous endarteritis, and a cellular infiltrate of the pulmonary parenchyma adjacent to the pulmonary arteries. From this point (100 days) forward, major differences in the pathogenesis of disease develop between the cat and dog. In the latter, most of the worms continue to develop into adulthood and the familiar progression of canine heartworm disease unfolds. In the cat, a majority of immature worms die at three to four months postinfection. This results in an inflammatory reaction and development of the syndrome known as heartworm associated respiratory disease (HARD).1 Demonstrable histopathological lesions are evident even in those cats who clear the infection, and are exactly the same as those found in cats with adult worms. The most notable microscopic lesion is occlusive medial hypertrophy of the small pulmonary arterioles, but other changes are also noted in the bronchi, bronchioles, alveoli, and pulmonary arteries.2 Medial hypertrophy can also occur from toxocara and aelurostrongylus infections.3 Radiographic signs are similar to those of feline asthma or allergic bronchitis, which can result in missed diagnoses. These images show a histopathologic view of arterioles from heartworm-challenged cats. A) The cat received a monthly heartworm preventative; B) A cat with abbreviated juvenile worm infection; C) A cat infected with adult heartworm. Photos courtesy Tom Nelson Rates of feline heartworm disease In experimental models, dogs infected with 100 L3 larvae will develop 75 adult worms in almost 100 percent of cases. Using the same model of 100 L3 larvae in cats, one to 10 adult heartworms will develop in 75 percent of cases. However, under real-world conditions, a very different picture emerges. Many factors determine the number of infective larvae a cat or dog is exposed to, including available vectors, reservoirs of infection, and temperatures conducive for larvae to develop. Necropsy surveys of shelter cats have placed the prevalence of adult heartworm infections at five to 20 percent of the rate seen in unprotected dogs in a given area. However, it should be stressed heartworm infection and heartworm disease are two different entities, with the former referring to the presence of live worms within the host animal and the latter being the pathology resulting from ongoing or past infection. A critical conclusion regarding HARD is that, while the damage caused by immature worms is not deadly, cats do not need to have adult heartworms present to develop significant pulmonary pathology. In a necropsy study that included histopathology of lungs, it was noted that in a group of shelter cats without adult heartworms but were heartworm-antibody positive, 50 percent of them had occlusive hypertrophy in 20 to 40 percent of arterioles. Experimental studies designed to mimic abbreviated heartworm infections reproduced these lesions in the pulmonary arterioles and the lesions where still present eight months after the infection. These thoracic radiographs show heartworm infection and broncho-interstitial lung pattern in a cat. A) Lateral view; B) Dorsoventral view; C) A closer view of an enlarged right caudal lobar pulmonary artery. Diagnostic testing recommendations Diagnosing feline heartworm disease can present significantly greater challenges than it does for that in dogs. Specifically, testing methodologies routinely used in diagnosing canine heartworm disease may have varying degrees of value for feline patients. Microfilaria testing: Filtration testing for microfilaria is virtually useless because the cat is only transiently microfilaremic, if at all. Radiology: Over half of heartworm-positive cats show radiographic signs,6 the most common of which is an enlargement of the right caudal lobar artery best seen in a ventral-dorsal view. A broncho-interstitial lung pattern is also found, but is not unique to feline heartworm disease. Other less commonly seen findings are hyperinflation of the lungs with flattening of the diaphragm, focal parenchymal radio-densities, consolidated lung lobes, pleural effusion, and pneumothorax.7 Ultrasonography: Ultrasound in the hands of a skilled ultrasonographer has been shown to detect 90 percent of adult feline heartworm infections; however, the ultrasonographer must be able to follow the caudal pulmonary arteries to the bifurcation within the lung fields.8 Serology: While antigen and antibody testing is readily available, there is an ongoing debate regarding the accuracy of both tests in feline patients. Antigen tests: Cats with adult infections typically have only one or two adult worms; single-sex infections, including male-only infections, are common. In addition, the majority of feline heartworm disease is caused by the death of immature worms at three to four months postinfection. Because antigen tests do not detect early or male-only worm infections, this can result in false-negative test results. In addition, antigen-antibody complexes can interfere with antigen testing, resulting in false-negative tests.9 Laboratory studies have shown heating the sample test tube to 104 C (219 F) for 10 minutes will break these complexes down and release any antigen, resulting in more positive test results. Most reference labs now offer heat treatment as an option when antigen test results are in question. A caveat: practitioners must be careful not to overinterpret a positive test on heat-treated samples, as it could indicate bound residual antigen from a worm that has recently died and is still in circulation. In other words, it does not necessarily mean live adult worms are present.10 Antibody tests also have limitations—a negative antibody test cannot be used to rule out heartworm infections. Whereas all antigen tests detect the same glycoprotein secreted from the reproductive tract of adult heartworms, not every antibody test is looking for the same antibody. In experimental studies, antibody tests initially detected 98 to 100 percent of heartworm infections,11 but have failed to perform at the same level of accuracy in naturally infected cats in real-world settings. We have now found a significant number of cats with adult heartworms are negative to antibodies. In a retrospective study of 50 heartworm-positive cats conducted at North Carolina State University, 14 percent were false negatives, while a large majority of these cats (72 percent) had clinical signs indicating active disease.12 Meanwhile, a necropsy study of shelter cats in Texas reported a 50 percent false negative,13 while another necropsy study of shelter cats in Florida had an 11 to 68 percent false negative14 on six different antibody test. Twenty-one of 31 heartworm-positive cats were negative on at least one of eight antibody tests evaluated.15 Two separate studies have compared multiple antibody tests, antigen tests, and radiographs in an effort to diagnose feline heartworm disease. The first study was on client-owned cats that were presented with a primary complaint of coughing.6 The second study was on shelter cats who had necropsy-confirmed heartworm status and histopathology of lungs.10 Both studies concluded no one test proved to be definitive in diagnosing FHWD, an array of diagnostic tests increased the ability to make a diagnosis, and FHWD is far more prevalent than our current diagnostic abilities are able to detect. The bottom line When using antigen and antibody tests, veterinarians need to be aware of their shortcomings. It is difficult to get a diagnosis of feline heartworm disease using a single method unless screening reveals a positive antigen test or a finding of a worm on ultrasound. Most cases require performing multiple tests, and veterinarians should be prepared to run additional tests if antigen or antibody results do not support clinical suspicions. References 1 Nelson CT, Seward RL, McCall JW, et al. Guidelines for the Diagnosis, Prevention, and Management of Heartworm (Dirofilaria immitis) Infection in Cats. American Heartworm Society, 2007. 2 Dillon AR, Blagburn B, Tillson DM, et al. Immature heartworm infection produces pulmonaryparenchymal, airway, and vascular disease in cats. J Vet Intern Med. 2007;21:608–609. 3 Dillon AR, Tillson DM, Hathcock J et al. Lung histopathology, radiography, high-resolution computed tomography, and bronchio-alveolar lavage cytology are altered by Toxocara cati infection in cats and is independent of development of adult intestinal parasites. Vet Parasitol. 2013;193:413–426. 4 Ryan WG, Newcomb KM. Prevalence of feline heartworm disease—a global review. In Proceedings of the Heartworm Symposium ’95, Auburn, AL. American Heartworm Society, 1995, pp 79-86. 5 Browne LE, Carter TD, Levy JK, et al. Pulmonary arterial disease in cats seropositive for Dirofilaria immitis but lacking adult heartworms in the heart and lungs. Am J Vet Res. 2005;66:1544-1549. 6 Dillon AR, Brawner WR, Robertson-Plough CK, Guerrero J. Feline heartworm disease: Correlation of clinical signs, serology, and other diagnostics. Results of a multicenter study. In Recent Advances in Heartworm Disease: Symposium ’98, American Heartworm Society, Tampa, FL. 1998:153-158 7 Brawner WR Jr, Dillon AR, Robertson-Plouch CK, Guerrero J. Radiographic diagnosis of feline heartworm disease and correlation to other clinical criteria: Results of a multicenter clinical case study. In Recent Advances in Heartworm Disease: Symposium ’98, Tampa, FL. American Heartworm Society, 1998, pp 91-95. 8 Atkins CE, Arther RG, et al. Echocardiographic quantification of Dirofilaria immitis in experimentally infected cats. Vet Parasitol. 2008;158(3):164-170. 9 Little SE, Raymond MR, Thomas JE, et al. Heat treatment prior to testing allows detection of antigen of Dirofilaria immitis in feline serum. Parasites Vectors. 2014;7:1. 10 Nelson CT. Comparison of Dirofilaria immitis antigen and antibody test results to gross necropsy, histopathology, and radiographic findings in adult shelter cats in NE Alabama. American Heartworm Society Symposium, New Orleans 2019 11 McCall JW. Evaluation of feline heartworm antibody test kits and diagnostic laboratory test. In Recent Advances in Heartworm Disease: Symposium ’01. American Heartworm Society, 2001, pp 125-134. 12 Atkins CE, DeFrancesco TC, Coats JR, et al. Heartworm infection in cats: 50 cases (1985-1997). J Am Vet Med Assoc. 2000;217:355-358. 13 Nelson CT, Self TS. Incidence of Dirofilaria immitis in shelter cats in southeast Texas. In Recent Advances in Heartworm Disease: Symposium ‘98, Tampa, FL. American Heartworm Society, 1998, pp 63-66. 14 Nelson CT, Self TS. Incidence of Dirofilaria immitis in shelter cats in southeast Texas. In Recent Advances in Heartworm Disease: Symposium ‘98, Tampa, FL. American Heartworm Society, 1998, pp 63-66. 15 Snyder PS, Levy JK, Salute ME, et al. Performance of serologic tests used to detect heartworm infection in cats. J Am Vet Med Assoc. 2000;216:693-700. Tom Nelson, DVM, is research chair for the American Heartworm Society (AHS) and medical director for VCA Animal Medical Center of NE Alabama in Anniston.
