Heartworm disease (dirofilariasis), produced by Dirofilaria immitis, primarily affects the pulmonary arteries, causing inflammation, endothelial remodeling, and vascular dysfunction. Secondarily, this results in pulmonary hypertension and right-sided cardiac pressure overload. Tertiary problems include right-sided heart failure, caval syndrome, coagulopathies (DIC), and aberrant heartworm migration. Most infected dogs are subclinically affected. When clinical signs are present, the most common is cough. With more severe disease, clinical signs may include exercise intolerance, labored breathing, abdominal distention (right-sided heart failure), syncope, and cachexia. Clearing a heartworm infection typically requires melarsomine, an organic arsenic compound; chronic use of certain macrocyclic lactones with doxycycline has also been effective. Consistent administration of preventatives containing macrocyclic lactones is crucial for prevention.
Heartworm disease is a potentially life-threatening parasitic disease caused by infection with heartworms (dirofilariasis). It is one of the most important parasitic diseases in veterinary medicine.
Etiology and Pathogenesis of Heartworm Disease in Dogs, Cats, and Ferrets
The etiological agent of heartworm disease is a filarial nematode of the genus Dirofilaria (synonym Nochtiella) in the family Onchocercidae.
While the canine heartworm (Dirofilaria immitis) is of greatest importance in companion animal medicine, approximately 40 species of Dirofilaria exist. Dirofilaria repens is a parasitic infection of dogs in Europe, Asia, and Africa and typically causes subcutaneous dirofilariasis. D tenuis is a parasite that resides in the subcutaneous tissues of raccoons (Procyon lotor) in North America and infrequently causes disease in humans.
D immitis primarily infects dogs and, less commonly, cats and ferrets. Patent infections are possible in numerous wild and companion animal species. Canids (especially dogs and coyotes) are the most prominent definitive hosts and principal reservoirs of D immitis. Animals are infected through the bite of mosquitoes carrying infective Dirofilaria larvae.
D immitis, as well as heartworms of the genus Acanthocheilonema, can also infect marine mammals (see Parasitic Diseases of Marine Mammals).
The endosymbiotic bacteria Wolbachia pipientis reside intracellularly within the uterus and lateral chords of filarid parasites, including D immitis, and are necessary for normal maturation, reproduction, and infectivity of the heartworm.
Wolbachia pipientis have also been implicated in the pathogenesis of filarial diseases, possibly through endotoxin production. Furthermore, studies have demonstrated that a primary surface protein of Wolbachia (wsp) induces a specific IgG response in hosts infected by D immitis. (See photomicrograph of W pipientis.)
Courtesy of Dr. Laura Kramer.
For veterinarians, the most important aspect of Wolbachia is its symbiotic relation with D immitis. If Wolbachia are eradicated, the heartworm becomes sterile and subsequently experiences a decrease in biomass. To accomplish this, doxycycline treatment has become an important part of the armamentarium against heartworms.
Pathogenesis of Heartworm Disease in Dogs
The severity of cardiopulmonary pathological changes in dogs is determined by the following factors:
heartworm numbers and viability
host immune response
duration of infection
host activity level
Live heartworms injure the pulmonary endothelium and incite inflammation via direct mechanical trauma and other suspected factors (eg, antigens and excretions). Macrophages, granulocytes, and platelets are attracted to sites of endothelial damage and contribute to a proinflammatory and proliferative milieu, leading to endarteritis and perivascular cuffing with inflammatory cells (especially eosinophils).
Death of microfilariae and the release of Wolbachia stimulate an immune response. Leakage of plasma and inflammatory mediators from small vessels and capillaries causes parenchymal lung inflammation (pneumonitis) and glomerulonephritis. Immune-mediated destruction of microfilaria also causes pneumonitis. These factors contribute to the cough that develops in some heartworm-infected dogs.
Long-term infections result in chronic vascular remodeling, subsequent scarring, progressive endothelial dysfunction, and pulmonary hypertension.
The presence of dead heartworms leads to more severe vascular reactions and subsequent pathological changes in the lung, even in areas not directly contacting dead heartworms. Dead worms also attract platelets, leading to thromboembolism.
Active dogs tend to develop pulmonary hypertension more often than inactive dogs for any given heartworm burden. Frequent exertion increases pulmonary arterial pathological changes and increases pulmonary artery resistance (with resultant pulmonary hypertension) and thereby may precipitate overt clinical signs, including right-sided congestive heart failure (R-CHF).
Pulmonary artery disease compromises vascular compliance, and this, with decreased ability to adequately vasodilate, results in increased flow velocity, especially with exertion. Resultant shear stresses further damage the endothelium. The process of endothelial damage, vascular dysfunction, increased flow velocity, and local ischemia is a vicious cycle. Inflammation with ischemia can result in irreversible interstitial fibrosis.
High heartworm burdens are most often the result of infections acquired from numerous mosquito exposures. High exposures in young, naive dogs in temperate climates can result in severe infections, possibly precipitating vena cava (caval) syndrome the year after. Caval syndrome can also develop in older dogs, presumably due to chronic infection, pulmonary hypertension, and R-CHF.
Caval syndrome is a consequence of severe pulmonary hypertension and decreased right ventricular function or a massive and simultaneous maturation of worms. Both scenarios lead to retrograde movement of heartworms into the right atrium and venae cavae and obstruction of venous return and subsequent decrease in right ventricular stroke volume.
Caval syndrome causes clinical signs of both "backward" (R-CHF) and "forward" (prolonged capillary refill time, poor pulse quality) heart failure and intravascular hemolysis (pallor, pigmenturia).
Dogs with caval syndrome often have a right-sided systolic heart murmur due to disruption of the tricuspid valve apparatus and tricuspid insufficiency.
The location of adult heartworms depends on the dog's size and worm burden. Increasing worm burden increases the risk for intracardiac worms and caval syndrome. The presence of intracardiac worms is more likely in small breed dogs (1).
Pathogenesis of Heartworm Disease in Cats and Ferrets
Feline heartworm infection occurs with a live tissue-phase larval infection or vascular phase immature adult or mature adult infection. However, cats are more resistant than dogs to infection with adult heartworms, with most immature heartworms in cats not surviving to maturity. Nevertheless, infections result in inflammatory vascular, bronchial, and interstitial pulmonary pathological changes and associated clinical signs (termed heartworm-associated respiratory disease, or HARD).
The arrival of immature heartworms to the pulmonary arteries and arterioles incites an intense vascular and pulmonary parenchymal inflammatory response (mediated by pulmonary intravascular macrophages) that contributes to the death of most worms. This inflammatory response results in the development of bronchitis and bronchoconstriction, leading to cough and clinical signs that mimic feline inflammatory airway disease (asthma or bronchitis). Some cats with immature adult worms will abort their infection, whereas others will develop adult heartworms.
Pulmonary arterial pathological lesions in cats and ferrets are similar to those in dogs; however, small arteries develop more severe muscular hypertrophy. Nevertheless, pulmonary hypertension with CHF is less common in cats than in dogs or ferrets. When the parasites die, pulmonary inflammation and thrombosis or embolism can lead to severe and sometimes fatal lung injury. In cats that survive, type II alveolar cells replace type I cells, which decrease oxygenation and cause permanent lung injury.
In ferrets, heartworm infection also causes pulmonary arteritis and pneumonitis. Because of ferrets' small size, heartworms are more commonly found within the heart and cranial and caudal vena cava. Sudden death in ferrets with heartworm infection is thought to be caused by pulmonary embolism.
Epidemiology of Heartworm Disease in Dogs, Cats, and Ferrets
The distribution of D immitis, the canine heartworm, depends on multiple factors:
presence of a competent mosquito vector
climate that favors mosquito reproduction and infective larval development
presence of a population to serve as a reservoir of infection (domestic or wild canids that are not receiving heartworm preventatives)
At least 70 species of mosquitoes can serve as intermediate hosts; Aedes, Anopheles, and Culex are the most common genera acting as vectors.
In tropical and subtropical latitudes, the transmission season is year-round. In temperate latitudes, transmission is seasonal, yet hard to predict, given variations in microclimate, temperature, the ability of larvae to pause and resume their development as temperatures fluctuate, and adaptation of mosquito vectors. Therefore, administering preventatives throughout the year in all climates is safest.
In companion animals, infection risk is greatest in dogs and cats housed outdoors, although any dog, cat, or ferret, indoor or outdoor, can be infected.
While heartworm infection rates in other companion animals, such as ferrets and cats, are lower than in dogs, they tend to parallel infection rates in dogs in the same geographic region. Other infections in cats, such as those caused by the feline leukemia virus or feline immunodeficiency virus, are not predisposing factors.
Infected mosquitoes can transmit heartworm infections to humans; however, there are no reports of such infections becoming patent. In a human, maturation of the infective larvae may progress to the point where they reach the lungs, become encapsulated, and die. The dead larvae precipitate granulomatous reactions called coin lesions, which are visible with thoracic radiography and can mimic the radiographic appearance of lung cancer.
Life Cycle of Heartworms in Dogs, Cats, and Ferrets
The life cycle of heartworms begins when mosquito vector species acquire microfilariae (a neonatal larval stage) while feeding on an infected host. Once ingested by the mosquito, microfilariae develop into the first larval stage (L1). They then molt into the second larval stage (L2) and again to the infective third stage (L3) within the mosquito in approximately 1–4 weeks, depending on environmental temperatures. This development phase takes 10–14 days when the mean ambient temperature is > 27°C (81°F) and the relative humidity is 80%.
When mature, the infective larvae migrate to the mosquito's labium. As the mosquito feeds, the infective larvae erupt through the tip of the labium, and with a small amount of hemolymph, onto the host’s skin. The larvae migrate into the bite wound, beginning the intramammalian phase of the life cycle. A typical Aedes mosquito can survive the complete development of < 10 larvae.
In canids and other susceptible hosts, infective larvae (L3) molt into a fourth stage (L4) in 3–12 days. After remaining in the host's subcutaneous tissue, abdomen, and thorax for approximately 2 months, L4 larvae undergo their final molt into immature adults at day 50–70, arriving in the cardiac and pulmonary arteries approximately 70–120 days after initial infection.
Only 2.5–4 cm long on arrival, heartworms rapidly grow within the pulmonary vasculature to adult forms (males approximately 15 cm long, females approximately 25 cm).
When immature adult heartworms first reach the lungs, blood flow forces them into the more distal small pulmonary arteries of the caudal lung lobes. As the parasites grow, they occupy larger and larger pulmonary arteries, occasionally moving into the right ventricle and even the atrium when the heartworm burden is high.
Gravid females produce microfilariae as early as 6 months after infection but more typically 7–9 months after infection.
Microfilariae are detectable in approximately 80% of infected canids not receiving macrolide prophylaxis but only occasionally in dogs placed on preventatives after having been infected. The number of circulating microfilariae does not correlate well to the adult female heartworm burden. Adult heartworms typically live 5–7 years, whereas microfilariae can survive for up to 2 years in a dog.
Most dogs are highly susceptible to heartworm infection, and in dogs, most (mean 56%) experimentally administered infective larvae (L3) develop into adults. Ferrets and cats are susceptible hosts; however, the infection success rate is low (an average of 6% in cats and 40% in ferrets).
In cats, the adult burden is often only 1–3 heartworms. Early death of heartworm larvae on arrival to the pulmonary vasculature appears to be largely responsible for heartworm-associated respiratory disease (HARD) syndrome in cats. HARD does not require maturation of heartworms but is due to the body’s response to dying and dead immature heartworms. When maturation does occur, adult heartworm survival in cats is typically not longer than 2–4 years.
Because cats and ferrets are abnormal hosts for D immitis, circulating microfilariae are uncommon. In all animals capable of being infected, aberrant larval migration can occur, resulting in parasitic lesions in the CNS, eye, scrotum, peritoneal cavity, and systemic arterial system, as well as in visceral and subcutaneous sites.
Clinical Findings of Heartworm Disease in Dogs, Cats, and Ferrets
See the table Diagnostic Tests, Clinical Signs, and Treatment for Dirofilariasis in Dogs, Cats, and Ferrets.
Diagnostic Tests, Clinical Signs, and Treatment for Dirofilariasis in Dogs, Cats, and Ferrets
Host | –-–----------------Diagnosis (Test Utility)-------------------- | Clinical Signs | Preventatives | ------------Treatment------------ | ||||
|---|---|---|---|---|---|---|---|---|
Microfilaria | Ag or Ab Test | Thoracic Radiography | Echocardiography | Adults | Microfilariae | |||
Dog | **** | ***** (Ag) | *** MPA, PA, RHE, PTE, PIE | ** | Respiratory, exercise intolerance, heart failure, weight loss | Ivermectin, milbemycin, selamectin, or moxidectin | Melarsomine, doxycycline, supportive treatment | Moxidectin,a ivermectin, milbemycin, or selamectin + doxycycline |
Cat | * | ** (Ag) *** (Ab)b | ** PA, PIE | **** | Respiratory, vomiting, sudden death, heart failure | Ivermectin, milbemycin, selamectin, moxidectin, or eprinomectinc | Supportive treatment, doxycycline, heartworm extraction | — |
Ferret | * | *** (Ag) | * RHE | *** | Heart failure, respiratory, sudden death | Ivermectin, milbemycin, selamectin, or moxidectind | Supportive treatment (including corticosteroids) | — |
Abbreviations: * = rarely useful; ** = somewhat useful; *** = moderately useful; **** = often useful; ***** = excellent test.; Ab, antibody; Ag, antigen; ML, macrocyclic lactone (macrolide); MPA, main pulmonary artery enlargement; PA, pulmonary artery enlargement; PIE, pulmonary infiltrate with eosinophils; PTE, pulmonary thrombosis or embolism; RHE, right heart enlargement. Adapted from McCall, JW. Clin Tech Small Anim Pract. 1998;13(2):112. aMoxidectin-imidacloprid is the only FDA-approved microfilaricide. bAb-positive result does not prove mature infection, only exposure/abbreviated infection. cDo not use in cats with the feline MDR1 mutation. dMoxidectin (in a formulation with the insecticide imidacloprid) is the only FDA-approved preventative in ferrets. | ||||||||
Clinical Findings of Heartworm Disease in Dogs
In dogs, heartworm infection is ideally identified by serological testing before onset of clinical signs; however, at the earliest, heartworm antigenemia and microfilaremia do not appear until approximately 5 and 6.5 months after infection, respectively. When dogs do not receive preventatives and are not appropriately tested, infection and disease progress undetected.
Clinical signs of heartworm disease in dogs include the following:
cough
exercise intolerance
unthriftiness
cyanosis
dyspnea
hemoptysis
syncope
collapse
ascites (in cases of right-sided CHF)
The severity of clinical signs in infected dogs is classified into 4 categories (see the table Classification of Heartworm Infection in Dogs).
Classification of Heartworm Infection in Dogs
Class | Clinical Signs |
|---|---|
Mild (class I) | No clinical signs or cough |
Moderate (class II) | Cough, exercise intolerance, abnormal lung sounds |
Severe (class III) | Cough, exercise intolerance, abnormal heart or lung sounds, dyspnea, hepatomegaly, syncope, ascites, death |
Caval syndrome (class IV) | Hemoglobinuria, anemia, low-output heart failure |
Most dogs have no, or only mild, clinical signs, and heartworm infection is incidentally diagnosed during routine blood screening. When clinical signs are present, cough due to pneumonitis is the most common complaint. Dogs without overt clinical signs usually do not have abnormal physical examination findings.
Dogs with more advanced heartworm infection may develop clinical signs relating to pneumonitis, pulmonary thrombosis or embolism (PTE), pulmonary hypertension, or elevated systemic venous pressures and R-CHF. Auscultation findings in animals with more advanced heartworm infection include the following:
increased lung sounds
adventitial lung sounds, such as crackles
right-sided systolic heart murmur (due to tricuspid valve insufficiency)
arrhythmia
With the progression of pulmonary hypertension and right-sided pressure overload, right ventricular stroke volume falls, leading to elevated systemic venous pressure and R-CHF. Clinical findings in dogs with R-CHF usually reflect elevated systemic venous pressures (jugular distention) and resultant cavitary effusions (usually ascites, although pleural effusion, small volume pericardial effusion, or subcutaneous edema is also possible).
Caval syndrome causes clinical signs of both "backward" (right-sided) congestive heart failure and "forward" heart failure (prolonged capillary refill time, poor pulse quality), as well as intravascular hemolysis (pallor, pigmenturia).
Clinical signs associated with caval syndrome include weakness, depression, collapse, and dyspnea. The pigmenturia in caval syndrome is hemoglobinuria due to microangiopathic hemolytic anemia caused by sieves of heartworms fragmenting RBCs in the circulation. Dogs with caval syndrome often have a right-sided systolic heart murmur due to disruption of the tricuspid valve apparatus and tricuspid insufficiency.
Clinical Findings of Heartworm Disease in Cats
Cats with heartworm infection may be subclinically affected or may develop severe disease. Clinical signs of heartworm disease in cats include the following:
intermittent coughing
dyspnea
vomiting
lethargy
anorexia
weight loss
syncope
right-sided heart failure (pleural effusion with or without ascites)
When evident, clinical signs in cats usually develop during 2 phases of the heartworm life cycle: the arrival of immature heartworms in the pulmonary vasculature (approximately 3–4 months after infection) and the death of adult heartworms.
Early clinical signs are associated with an acute vascular and parenchymal inflammatory response to immature heartworms and the subsequent death of many or all of these worms. This initial phase is often misdiagnosed as feline inflammatory airway disease (asthma or bronchitis).
Cats that abort an immature adult infection will not have detectable antigen. Cats with mature adult infection usually do not have detectable antigen due to low worm burden and are also usually amicrofilaremic. In both scenarios, results of the heartworm antibody test may be positive, yet currently available tests lack sensitivity in naturally infected cats, and a negative antibody test result doesn't necessarily rule out a current or past infection (2).
The natural history of disease in cats with aborted infection and respiratory signs is not well characterized. Clinical signs may permanently resolve in some cats, whereas others have chronic respiratory signs. Clinical signs such as syncope and R-CHF (pleural effusion with or without ascites) are uncommon and most likely to occur in cats with mature adult infections.
In cats harboring mature adult heartworms, death of even one worm can lead to acute respiratory distress and shock, which can be acutely fatal and appears to be the consequence of pulmonary thrombosis or anaphylactic-like shock.
Clinical Findings of Heartworm Disease in Ferrets
Clinical signs in ferrets, more so than in cats, are similar to those of heartworm infection in dogs. However, as in cats, the large parasite:host body weight ratio dictates that ferrets develop clinical signs with relatively small heartworm burdens.
Clinical signs in ferrets with heartworm disease include the following:
weight loss
fatigue
cough
rapid or labored breathing
heart murmur
distended and pulsatile jugular veins (CHF)
gray and cold mucous membranes
ascites
pleural effusion
fainting
sudden death
Diagnosis of Heartworm Disease in Dogs, Cats, and Ferrets
Serological testing
Detection of microfilariae
Diagnostic imaging
Ancillary testing
Heartworm Detection in Dogs
The antigen detection test is the preferred diagnostic method for routine screening or when seeking verification of a suspected heartworm infection. Antigen testing is the most sensitive and specific diagnostic method available to veterinary practitioners.
Microfilaria testing is limited by the fact that approximately 20% of infected dogs are amicrofilaremic. This percentage is even higher for dogs that are infected with adult heartworms and consistently administered monthly or long-term formulations of macrolide prophylaxis, because this kills microfilariae and induces embryostasis in mature female dirofilariae.
Microfilaria testing still has value because a small percentage of heartworm-infected dogs are antigen-negative and microfilaria-positive, allowing an otherwise missed diagnosis to be made. For this reason, especially in endemic areas, combining a microfilaria test (eg, modified Knott test, microfilaria filter-concentration test, drop of fresh blood under coverslip, microscopic evaluation of buffy coat in microhematocrit tube) with the antigen test should be considered for routine annual screening.
At a minimum, checking for microfilariae is critical when antigen test results are positive, due to the need to understand microfilarial burden and hence risk of reaction to the first macrocyclic lactone administration.
Timing of antigen testing is critical and should take into account the prepatent period, or the time from exposure to seroconversion (ie, when antigen test results will be positive). Because these tests detect only adult female heartworms, a reasonable interval is 7 months after last possible exposure. There is no value in testing a dog for antigen or microfilariae before approximately 7 months of age.
To ensure that a previously acquired infection does not exist in young dogs, they should be tested 6–7 months after beginning heartworm prophylaxis. For dogs > 7 months old and not on heartworm prophylaxis, testing should be performed at that time and 7 months after initiating treatment with preventatives. Subsequently, annual antigen detection tests are recommended. This same rationale is applied to testing dogs after a lapse in macrolide prophylaxis.
Although antigen tests are highly sensitive, false-negative results do occur. Some experts use the terminology “no antigen detected” in place of "negative results" to underscore the possibility of a false-negative result. False-negative test results may be caused by antigen-antibody complexing, immature or all-male infections, or low numbers of female heartworms.
If the negative result is unexpected, heat treatment helps “unmask” antigen-antibody complexing and may increase test sensitivity in the case of low worm burden or all-male infections. Heat treatment causes immune complex dissociation in samples where antibody has bound the heartworm antigen, thereby freeing the antigen for detection.
Heat-treatment tests are available at many commercial diagnostic labs. Heat treatment of serum should be considered in cases where heartworm disease is suspected, yet no antigen is detected, such as a dog with a negative test result accompanied by D immitis microfilaremia or clinical signs or by diagnostic test results supportive of heartworm infection, especially when the animal is from an endemic region and is receiving no or inconsistent macrocyclic lactone preventatives
Heat treatment is not recommended for routine screening or retesting an animal after arsenical adulticide therapy because the meaning of positive results after adulticide administration is not well established. For example, a heat-treated sample during a routine recheck antigen test 9 months after initiating an arsenical adulticide protocol may yield a positive result due to detection of low levels of residual antigen released after adult heartworm death. It is also not known whether heat treatment leads to detection/cross-reaction of off-target epitopes formed after denaturation. For kits including additional tests (eg, tickborne disease), heat treatment destroys antibodies and invalidates the results of these tests.
A positive microfilaria test result in conjunction with a positive antigen test result is confirmatory of heartworm infection. If the microfilaria test result is negative, a second antigen test, ideally using a different type of assay, should be performed for confirmation before adulticide therapy.
Pearls & Pitfalls
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In dogs, echocardiography is relatively unimportant as a diagnostic tool, although it can allow assessment of cardiac damage and performance in dogs with clinical or radiographic signs of pulmonary hypertension and/or R-CHF. Visualization of heartworms in the right heart and vena cava is associated with high-burden infection with or without caval syndrome. Severe, chronic pulmonary hypertension causes right ventricular hypertrophy, septal flattening, underloading of the left heart, and high-velocity tricuspid and pulmonary valve regurgitation.
Point-of-care ultrasonography or echocardiography is useful to confirm intracardiac worms in dogs with clinical signs of caval syndrome (pigmenturia, anemia, signs of low cardiac output). The echogenic cuticles of the heartworm will appear as hyperechoic parallel lines that look like long, bright equal signs (see 4-chamber and short-axis view echocardiograms).
Courtesy of Dr. Marisa K. Ames.
Courtesy of Dr. Marisa K. Ames.
Findings on echocardiography are usually normal in infected dogs. However, right ventricular hypertrophy patterns are observed in severe, chronic pulmonary hypertension, often associated with overt or impending R-CHF (ascites). Cardiac rhythm disturbances are usually absent or mild; however, atrial fibrillation is an occasional serious complication in dogs.
Heartworm Detection in Cats and Ferrets
The diagnosis of heartworm infection in cats is based on historical and physical findings, index of suspicion, and results of thoracic radiography, echocardiography, and serological testing.
Cats may show positive antigen test results 7–8 months after L3 inoculation. However, antigen tests alone are considered too insensitive as the sole screening test for cats.
False-negative results occur with low female worm burdens, clinically apparent immature infections, all-male infections, and antigen-antibody binding. Nevertheless, the antigen test is recommended in cats in which heartworm infection is suspected.
Heat treatment increases the sensitivity of the antigen test and should be considered in cats at high risk of heartworm infection or cats in which heartworm disease is suspected. For kits including additional tests (eg, FIV), heat treatment destroys antibodies and invalidates the results of these tests.
Antibodies against heartworms appear 2–3 months after L3 infection and are generally detectable by 5 months. Antibodies can persist at detectable concentrations for several months after heartworm death. In addition, antibodies induced by larvae can persist in aborted infections and after macrolide prophylaxis has been instituted, killing the early larval stages. Thus, a positive antibody test result indicates that an infection (aborted larval or mature adult) occurred but does not guarantee a current infection.
Antibody seropositivity identifies cats at risk that should receive regular macrolide preventatives. False-positive results from cross-reactivity with other parasites have not been observed. Because currently available antibody tests have relatively low sensitivity in naturally infected cats, a negative antibody test result does not rule out exposure or infection. Microfilariae are rarely detected (< 10%) in cats, regardless of the method used.
Pearls & Pitfalls
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Annual screening of cats informs veterinarians and owners of the risk of heartworm infection yet is not necessary before initiating macrolide preventatives.
Because of the relative sizes of the heartworms and the right heart and pulmonary arterial system of cats, heartworms can often be visualized using echocardiography.
Heartworms, particularly females, are long enough to occupy the pulmonary arteries as well as the right heart, where they can be easily visualized. Parallel hyperechoic lines, produced by the heartworm cuticle, may be observed in the right heart and pulmonary arteries. Echocardiography is more important in cats than in dogs because of the increased difficulty of diagnosis in cats (low antigen test sensitivity and low antibody test specificity for mature infection) and the relatively high sensitivity of echocardiography when performed by an experienced operator (see mature heartworm infection, echocardiogram, cat).
Courtesy of Dr. Marisa K. Ames.
In ferrets, commercial antigen tests have detected heartworm antigen in experimental infection as early as 5 months after infection and are effective in clinical situations. False-negative results can occur, especially in species that harbor lower heartworm burdens (cats and ferrets). Furthermore, although microfilaria testing is only rarely helpful, adult heartworms can often be observed with echocardiography and nonselective angiography.
Ancillary Tests for Heartworm Detection in Cats, Dogs, and Ferrets
In addition to antigen, antibody, and microfilaria tests in cats and dogs, a CBC, chemistry profile, urinalysis, and particularly thoracic radiography are sometimes indicated. Laboratory data are often normal.
Eosinophilia and basophilia alone or together may occur in dirofilariasis. Eosinophilia is most often observed at the time that immature adults arrive in the pulmonary arteries. Subsequently, eosinophil counts vary but are usually high in dogs with immune-mediated clearance of microfilaria, especially if eosinophilic pneumonitis develops.
Anemia in heartworm-infected dogs occurs due to chronic inflammation (usually mild) and due to hemolysis (more severe) during caval syndrome.
Hyperglobulinemia, due to antigenic stimulation, may be present in dogs and cats.
Hypoalbuminemia in dogs can be associated with proteinuria in severe immune-complex glomerulonephritis or with severe emaciation (as in cardiac cachexia). Occasionally, severe glomerulonephritis can lead to hypoalbuminemia and nephrotic syndrome. Dogs with hypoalbuminemia, secondary to glomerular disease, also lose antithrombin III and are at risk of thromboembolic disease.
Serum ALT and alkaline phosphatase activities are occasionally increased but do not correlate well with abnormal liver function, efficacy of adulticide treatment, or risk of drug toxicosis.
Urinalysis may reveal proteinuria that can be quantitated by a urine protein:creatinine concentration ratio.
Hemoglobinuria is associated with caval syndrome and occurs when RBCs are lysed in the circulation.
In dogs, thoracic radiography provides the most information on disease severity and is particularly important in patients with clinical signs. High-risk infections are characterized by a large main pulmonary artery segment and dilated, tortuous caudal lobar pulmonary arteries. Right ventricular enlargement may also be observed and, along with enlarged pulmonary arteries, is indicative of pulmonary hypertension. With PTE and pulmonary infiltrate with eosinophils (pneumonitis), ill-defined parenchymal infiltrates surround the caudal lobar arteries, typically most severe in the right caudal lobe.
See lateral and ventrodorsal radiographs (mild lesions) and left lateral and ventrodorsal radiographs (severe lesions).
Courtesy of the University of Florida.
Courtesy of the University of Florida.
Courtesy of Dr. Marisa K. Ames.
Courtesy of Dr. Marisa K. Ames
In cats, cardiac changes and pulmonary hypertension are less common. In approximately 50% of infected cats, caudal lobar arteries are larger than the corresponding vein and > 1.6 times the diameter of the 9th rib at the 9th intercostal space. Patchy parenchymal infiltrates and/or a bronchial pattern may also be present in cats with respiratory signs. The main pulmonary artery segment is usually not visible because of its relatively midline location in cats. (See radiographs of presumed aborted larval infection and mature heartworm infection, cat.)
Courtesy of Dr. Marisa K. Ames.
Courtesy of Dr. Marisa K. Ames.
In ferrets, radiography can demonstrate cardiac and pulmonary arterial changes compatible with heartworm disease. In addition, adult heartworms can often be observed with echocardiography and nonselective angiography.
Treatment of Heartworm Disease in Dogs
Doxycycline, a 3-dose melarsomine protocol, and exercise restriction
Nonarsenical protocols using ivermectin where melarsomine is unavailable or contraindicated
Pretreatment Evaluation for Heartworm Treatment in Dogs
The extent of the preadulticide evaluation varies, depending on the clinical status of the dog, the likelihood of coexisting diseases that may affect treatment outcome, and cost considerations. Clinical laboratory and imaging data should be collected selectively to complement information obtained from a thorough history, physical examination, and antigen and microfilaria tests.
Two important variables are known to directly influence the probability of posttreatment thromboembolic complications and treatment outcome: the extent of concurrent pulmonary vascular disease and the current heartworm burden. Although there is no effective way to determine heartworm burden, prevention history, geography, and age can be used to assess a dog's risk for heavy infection.
Pulmonary thromboembolic complications after adulticide treatment are most likely to occur in dogs already exhibiting clinical and radiographic signs of severe pulmonary vascular disease, especially when severe pulmonary hypertension and CHF are present. However, thromboembolic complications can occur in dogs that had no clinical signs at diagnosis, especially when activity is not restricted. Exercise restriction is crucial to reducing complications, regardless of clinical status and adulticide protocol used.
Before adulticide treatment, heartworm-infected dogs are assessed and rated for high or low risk of postadulticide thrombosis or embolism.
Dogs in the low-risk category would ideally fulfill the following conditions: young, no clinical signs, normal findings on thoracic radiography, no heartworms visualized by echocardiography, and no concurrent disease, as well as having owners capable of completely restricting exercise. The low-risk group would also include dogs that have previously undergone adulticide treatment but remain antigen-positive (presumed low heartworm burden).
Dogs at high risk of thromboembolic complications include those with clinical signs related to heartworm infection (eg, frequent coughing, dyspnea, ascites), abnormal findings on thoracic radiography, intracardiac heartworms visualized by echocardiography, concurrent disease, and little or no possibility that the owners will restrict activity.
After evaluation, risk assessment, and financial considerations, an adulticide protocol is chosen. (See the table Guide to Choosing a Heartworm Treatment Protocol.)
A minimum database (CBC, serum biochemistry, urinalysis) and thoracic radiographs are ideal in any dog with heartworm infection; these tests establish a baseline, should complications arise, and screen for concurrent systemic disease. Dogs with normal or near-normal findings on baseline thoracic radiography may develop severe thromboembolic disease, especially when activity is not restricted. That said, in dogs without clinical signs, treatment should be prioritized over additional diagnostic tests when finances are a concern.
A heartworm preventative (injectable, topical, or oral) that fits the owner's lifestyle should be initiated and continued year-round for the rest of the dog's life. Activity restriction is recommended for all protocols, which are listed below:
doxycycline and split-dose melarsomine (three doses)
doxycycline and two-dose melarsomine
nonarsenical adulticide: doxycycline, preventive dosage of ivermectin or moxidectin
nonarsenical adulticide ("slow-kill"): preventive dosage of ivermectin or moxidectin (not recommended; see below)
Preparing for Adulticide Therapy in Heartworm Treatment in Dogs
In most dogs, once the diagnosis of heartworm infection is made, the protocol for adulticide treatment can be started.
A macrocyclic lactone preventative and doxycycline (10 mg/kg, PO, every 12 hours for 4 weeks) should be initiated at the time of diagnosis in all dogs. Doxycycline has become an important part of treatment of heartworm infection in dogs. Through its negative action on Wolbachia, doxycycline provides benefits to the canid host and works to the detriment of D immitis.
Pearls & Pitfalls
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Doxycycline decreases the severity of lung injury after adulticide treatment, probably by decreasing the amount of Wolbachia antigen and the proteins released from the heartworm uterus as the bacteria die and the uterus degenerates. Doxycycline treatment hastens heartworm death when a nonarsenical protocol is used, thereby presumably decreasing the negative impact of heartworms on the host. Doxycycline paired with a macrocyclic lactone also clears the host of microfilariae. Therefore, in dogs undergoing nonarsenical treatment protocols, this combination decreases the risk of macrolide resistance.
Doxycycline administration is indicated when treating dogs with heartworm infection regardless of disease severity classification or protocol. Doxycycline is effective at killing migrating tissue-phase heartworms (L3/L3-L4 molt and L4). Microfilaria picked up from dogs that have received the recommended course of doxycycline will mature to L3 within the mosquito, yet the resulting L3 will not be capable of establishing a successful infection in the next dog.
Doxycycline should be given with food to decrease GI upset. If the drug is not tolerated, reducing the dosage to 7.5 mg/kg or 5 mg/kg may be indicated. Minocycline can be substituted at the same dosages when doxycycline is not available.
A 30-day waiting period after the completion of the doxycycline course is recommended; this delay allows for more dissipation of Wolbachia metabolites and further weaning of the worm before melarsomine. Melarsomine injections are started 2 months after diagnosis. In shelter/rescue practices, this wait period is sometimes shortened or removed to speed up the treatment protocol.
Pretreatment Stabilization in Heartworm Treatment in Dogs
Cough and/or tachypnea in dogs with heartworm infection before adulticide administration is most often due to pneumonitis, and a tapering course of steroids is indicated (prednisone/prednisolone 0.5 mg/kg, PO, every 12 hours for 7 days; then 0.5 mg/kg, every 24 hours for 7 days; then 0.5 mg/kg, every 48 hours for 2 weeks). This course can be tapered more slowly in dogs with refractory cough.
The timing of the first melarsomine injection can be delayed in very sick dogs (ie, while R-CHF is controlled). For treatment recommendations, see Heart Failure in Dogs and Cats.
Ideally, the diagnosis of pulmonary hypertension is supported by echocardiography. However, severe pulmonary hypertension is usually a major factor leading to R-CHF in dogs with heartworm infection, and sildenafil is a reasonable choice for empirical treatment. Sildenafil is a pulmonary arterial vasodilator (usually started at 1 mg/kg, PO, every 8 hours, then up-titrated to 2 mg/kg, PO, every 8 hours as clinically indicated). Sildenafil is usually a long-term medication that may be able to be discontinued once the infection is successfully controlled.
An arsenical adulticide can be initiated if the R-CHF is well controlled. If the R-CHF is refractory to medical therapy, the prognosis is guarded, and a nonarsenical approach could be considered.
In caval syndrome, removal of heartworms from the right atrium and orifice of the tricuspid valve is typically necessary to save the dog's life. The patient is usually placed under general anesthesia, though sedation and local anesthetic blocking of the venotomy site may be enough in severely compromised patients. With the patient in left lateral recumbency, the right jugular vein is surgically prepared and draped. The right jugular vein is exposed, and a 2–3 mm venotomy is created. Silk sutures, tied in open loops proximal and distal to the venotomy site, help with manipulation of the vessel and provide hemostasis. If available, fluoroscopy or transesophageal or transthoracic echocardiography is used to direct the retrieval equipment within the right heart.
Retrieval instruments include rigid alligator forceps, flexible alligator forceps (as described by Ishihara et al), nitinol gooseneck snare kits, endovascular snares, and endoscopic retrieval baskets. The retrieval device is directly introduced into the venotomy site, yet great care must be taken when handling the jugular vein to prevent trauma and hemorrhage. Excessive force (pulling the snare or basket too hard into its catheter or tension on grasping forceps) should be avoided when using the retrieval equipment to grasp or ensnare; otherwise, worm laceration and release of antigen with subsequent anaphylaxis can result.
Once there are several negative passes through the vein with the retrieval device, or transthoracic or transesophageal echocardiography confirms a successful decrease of worm burden, the venotomy is ligated or repaired, and the skin incision is closed in routine fashion. Medical stabilization is continued after the procedure.
In dogs, doxycycline and initiation of a macrocyclic lactone preventative can be started during the initial hospitalization, before or after worm removal. The timing of melarsomine injections can follow the American Heartworm Society protocol or be delayed until all adverse sequelae of caval syndrome (heart failure, pulmonary hypertension) are medically controlled.
Arsenical (Melarsomine) Adulticide Heartworm Treatment Protocol in Dogs
The only approved heartworm adulticide is melarsomine dihydrochloride, which is effective against mature (adult) heartworms of both sexes, with male heartworms being more susceptible.
The American Heartworm Society recommends initiation of a macrocyclic lactone preventative and a course of doxycycline (10 mg/kg, PO, every 12 hours for 4 weeks; decreased to 7.5 or 5 mg/kg, PO, every 12 hours if not tolerated) at the time of diagnosis. One month after the completion of the doxycycline course (2 months after initiation of treatment), adulticide injections are initiated as the dog's condition allows.
At the initiation of therapy, a tapering course of steroids (prednisone/prednisolone 0.5 mg/kg, PO, every 12 hours for 7 days; then 0.5 mg/kg, PO, every 24 hours for 7 days; then 0.5 mg/kg, PO, every 48 hours for 2 weeks) is recommended in dogs with clinical signs of heartworm infection. This course can be tapered more slowly in dogs with refractory cough. The tapering course of steroids is recommended in all dogs after their melarsomine injections. The rationale for the tapering courses of steroids during the treatment protocol is to decrease the inflammation associated with pneumonitis and to decrease thrombosis around the dead and dying heartworms within the pulmonary arteries.
Melarsomine (2.5 mg/kg, deep IM in the belly of the epaxial [lumbar] musculature in the area of the third to fifth lumbar vertebrae, at intervals as recommended by the American Heartworm Society) is administered using the following recommended needle sizes in dogs:
dogs ≤ 10 kg: use a 23-gauge, 2.5-cm (1-inch) needle
dogs > 10 kg: use a 22-gauge, 3.8-cm (1.5-inch) needle
On each administration, the left and right sides should be alternated. Superficial injection should be avoided. Pressure at the injection site should be applied and maintained for 5 minutes to prevent drug migration.
Approximately one-third of dogs develop local clinical signs of pain, swelling, soreness with movement, or rarely, sterile abscess formation at the injection site. Local fibrosis is not uncommon (and is the reason for targeting the belly of the epaxial musculature).
The American Heartworm Society recommends the 3-dose melarsomine protocol, regardless of the stage of disease or risk category. Using this protocol, a single injection of melarsomine is given; then, 30 days later, two injections are given 24 hours apart.
In the 2-dose melarsomine protocol, 2 injections of melarsomine, separated by 24 hours, are given 30 days after the doxycycline course is completed. In the shelter/rescue setting, the 30 day waiting period is sometimes eliminated to decrease the duration of treatment.
Exercise restriction is critical to minimize the risk of PTE due to dead and dying adult heartworms. Although exercise is minimized from the day of diagnosis, crate rest must be enforced for 6–8 weeks after the final injection. If, after the first injection, the dog displays substantial pulmonary damage from the resultant heartworm death, the same assessments discussed in the pretreatment stabilization section can be undertaken.
For the utility and advisability of various treatment protocols, see the table Guide to Choosing a Heartworm Treatment Protocol.
Guide to Choosing a Heartworm Treatment Protocol
Protocol | Efficacy | Disadvantages | Utility | |
|---|---|---|---|---|
1 | Three-dose (split-dose): melarsomine and doxycycline; activity restriction during protocol and 6–8 weeks after final injection | Kills 99% of heartworms (renders most dogs antigen-negative) | Requires the most veterinary visits of any protocol | Appropriate for all; best approach for all stages of heartworm disease; this is the protocol recommended by AHS |
2 | Two-dose: melarsomine and doxycycline; activity restriction during protocol and 6–8 weeks after final injection | In studies without doxycycline, this protocol kills 90% of heartworms (clears approximately 75–80% of dogs); doxycycline likely improves the kill | Greater risk for respiratory complications and lower kill compared to 3-dose protocol | Consider in rescue or shelter settings when there are time and/or financial constraints; appropriate for dogs with mild to moderate heartworm disease |
3 | Nonarsenical adulticide treatment: ivermectin, or moxidectin with doxycycline; activity restriction for months (ideally until antigen-negative) | Approximately 95% of dogs will have "no antigen detected" test result within 1 year | Lung disease progression; time of heartworm death unknown. Risk remains for respiratory complications during nonarsenical protocols. | Appropriate when melarsomine is not available, the dog has had prior life-threatening reaction to melarsomine, or the dog has a comorbidity with a guarded to grave prognosis |
4 | Slow-kill nonarsenical adulticide treatment with ivermectin, or moxidectin at preventive dosage; activity restriction for months (ideally until antigen-negative) | Likely takes more than 2 years of continuous administration before a "no antigen detected" test result | Risk of selecting for resistant strains of microfilariae; lung disease progression; time of heartworm death unknown. Risk remains for respiratory complications during nonarsenical protocols. | Not recommended; must clear microfilariae; ideally also use an insecticide product to prevent mosquitoes from picking up microfilariae |
Abbreviations: AHS = American Heartworm Society | ||||
Nonarsenical (Macrolide + Doxycycline) Adulticide Heartworm Treatment in Dogs
An arsenical (melarsomine) adulticide heartworm treatment protocol is the only FDA-approved approach and is the American Heartworm Society's recommendation for treating heartworm. However, lack of access to care and other concerns, as well as melarsomine availability, may dictate the need for alternatives. Cases in which nonarsenical adulticide treatment might be considered include the following:
melarsomine shortage or lack of access
history of life-threatening adverse reaction to melarsomine
comorbid condition conferring guarded to grave prognosis
Most options have focused on the use of macrocyclic lactones in a nonarsenical or slow-kill approach. This is controversial, largely because of the duration of treatment, yearslong reliance on patient compliance, ongoing host damage, and concern for resistance development.
Studies have shown that moxidectin and ivermectin have better adulticidal effect than selamectin and milbemycin. Doxycycline likely increases the efficacy of a macrocyclic lactone–based adulticide regimen and should be included in any nonarsenical adulticide protocol.
Several small studies have evaluated the combination of ivermectin or moxidectin (topical and injectable) and doxycycline in dogs with experimental and natural infections. Although the macrocyclic lactone–doxycycline protocols used in these studies appear to be safe and rendered most dogs "no antigen detected" on a conventional antigen test within 1 year, larger prospective studies are still needed.
A 4-week course of doxycycline (ideally 10 mg/kg, PO, every 12 hours) should be initiated at the time of diagnosis. Complications such as pneumonitis, thrombosis, and PTE are still possible, and exercise restriction should be imposed for months when using a nonarsenical protocol.
An antigen test should be repeated 10 months after initiation of the nonarsenical protocol.
If the antigen test result is positive, continue macrocyclic lactone treatment and repeat the antigen test in 3 months.
If a "no antigen detected" result is obtained, retest with a heat-treated antigen test. If this test has a "no antigen detected" result, then the heartworm infection has presumably been cleared; if the heat-treated test result is positive, macrocyclic lactone treatment is continued, and the test is repeated again in 3 months.
Macrocyclic lactone treatment should be considered lifelong in dogs that have had heartworm infection.
The rationale for using heat treatment in this scenario is that the use of doxycycline and macrocyclic lactones in dogs with heartworm infection increases the likelihood of antigen-antibody complexing and false-negative test results.
Certain canine breeds and individual dogs with polymorphisms in the MDR1 (ABCB1) gene encoding the multidrug efflux pump P-glycoprotein at the blood brain barrier are more susceptible to macrocyclic lactone CNS toxicity. (See discussion in Antiparasitic Drugs for Integumentary Disease in Animals.) Chronic use or use of doses higher than the labeled preventive dosage of these medications should be carefully considered before using in these dogs.
After Adulticide Heartworm Treatment in Dogs
Acute adverse effects after melarsomine injection may include pain, coughing, gagging, and hypersalivation. Treatment of these adverse effects consists of managing the clinical signs.
If an anaphylaxis-like reaction is suspected, treatment should include diphenhydramine (2 mg/kg, IM, every 8–12 hours during hospitalization), dexamethasone (0.1–0.2 mg/kg, IV, every 24 hours during hospitalization), and supportive care.
Adverse effects related to worm death typically occur within 5–10 days after melarsomine injection and include lethargy, GI signs (inappetance, vomiting, diarrhea), and cough. Treatment of these adverse effects consists of managing the clinical signs.
The exact mechanisms for GI signs associated with heartworm infection and adulticide therapy are not known.
PTE may occur in dogs after adulticide therapy as worms die and disintegrate (usually 1–3 weeks after a melarsomine injection or at variable times during nonarsenical protocols). Prevention of PTE by strictly curtailing activity for 6–8 weeks after the final melarsomine injection is extremely important.
D-dimer concentration, when used to monitor dogs before, during, and after adulticide therapy, is variably elevated, appears to correlate to worm burden, and is typically highest 2 weeks after adulticide administration.
Therapy for PTE usually consists of supportive care and individually tailored acute and chronic pharmacotherapy. Strict cage confinement, oxygen administration via oxygen cage or nasal insufflation (50–100 mL/kg/min), and dexamethasone (0.1–0.2 mg/kg, IV, every 24 hours during hospitalization) or prednisone/prednisolone (0.5 mg/kg, PO, every 12 hours, followed by a taper) has been the regimen advocated for severely affected dogs.
No consensus exists regarding the use of antithrombotics such as clopidogrel (1–2 mg/kg, PO, every 24 hours). Novel anticoagulants (eg, factor Xa inhibitors such as apixaban and rivaroxaban) hold promise for PTE therapy but haven't yet been studied in this situation.
The pulmonary vasodilator sildenafil (1 mg/kg PO, every 8 hours) and the positive inotrope pimobendan (0.25 mg/kg, PO, every 12 hours) are used empirically as long as needed when there is evidence of severe pulmonary hypertension.
Laboratory findings associated with adulticide treatment may include the following:
inflammatory leukogram
thrombocytopenia
prolonged activated clotting time or prothrombin time
increased serum CK activity
Antigen testing should be performed 9 months after the final dose of melarsomine. If a positive test result is obtained at this time, consideration can be given to abbreviated retreatment (2 melarsomine injections, 2.5 mg/kg, deep IM as described in the package labeling, 24 hours apart) or a nonarsenical approach with ivermectin or a moxidectin-imidacloprid combination product, at preventive dosages. The course of doxycycline (10 mg/kg, PO, every 12 hours for 4 weeks) should be repeated regardless of which protocol is chosen.
Microfilaricide Heartworm Treatment in Dogs
If not already being used, a macrocyclic lactone preventative is initiated when heartworm infection is diagnosed. Although all FDA-approved macrocyclic lactones have microfilaricide activity, only moxidectin (in combination topical products also containing imidacloprid) is labeled for use as treatment of circulating microfilariae.
Milbemycin oxime is also an effective microfilaricide yet does not carry a label for this. Selamectin and ivermectin will decrease microfilarial numbers but may not clear microfilaria. Doxycycline speeds the clearance of microfilaria when paired with any of these macrocyclic lactones.
Preparations of macrocyclic lactones intended for use in livestock should not be used in dogs or other small animals due to the risk of death or other severe adverse effects related to dose calculation error and accidental overdose.
Performance of a microfilaria test is recommended at the time of diagnosis and 1–3 months after microfilaricide treatment has begun.
Hypersensitivity reactions are a risk after macrocyclic lactone therapy in dogs with microfilaria. Care should be exercised when preventatives are administered to dogs with heavy microfilarial burdens. This care ranges from observation at home on the day of administration to hospitalization with or without pretreatment with corticosteroids and antihistamines.
Although uncommon in dogs, hypersensitivity reactions after macrocyclic lactone administration may develop within hours, with clinical signs ranging from vomiting and salivation to depression and shock. Treatment should include diphenhydramine (2 mg/kg, IM, every 8–12 hours during hospitalization), dexamethasone (0.2 mg/kg, IV, every 24 hours during hospitalization), and fluid therapy. Diphenhydramine and dexamethasone can also be used as a pretreatment to decrease the chances of an adverse reaction in dogs with heavy microfilarial burdens.
Treatment of Heartworm Disease in Cats
Heartworm infections are more often lethal in cats than in dogs; however, some cats survive infection without demonstrable clinical signs. The lifespan of adult heartworms in cats is thought to be 2–4 years, so spontaneous recovery is possible. Cats may remain subclinically affected, experience sudden death, or have clinical signs including episodic vomiting, coughing, dyspnea (resembling asthma), syncope, or rarely, clinical signs of R-CHF.
Melarsomine is not recommended for use in cats due to the risk of severe pulmonary inflammation and death, and most cases are managed conservatively. The cat should be started on a macrocyclic lactone to prevent new infection. Macrocyclic lactones are generally safe to administer to cats with adult heartworm infection. Cats typically have a low adult worm burden and do not have circulating microfilaria because of immune clearance. Hence, the concern that a hypersensitivity reaction could develop as a result of microfilaria death is largely eliminated.
A slow-kill approach using doxycycline (10 mg/kg, PO, every 12 hours for 4 weeks) and a macrocyclic lactone with adulticidal activity (moxidectin or ivermectin) may be used in cats. Possible adverse effects associated with doxycycline include esophageal injury, nausea, vomiting, and inappetence. Measures to help minimize the risk of adverse effects include reducing the dose to 7.5 or 5 mg/kg and administering doxycycline in a liquid formulation or immediately chasing tablets or capsules with 5–6 mL of water.
Oral and/or inhaled steroids are used to control respiratory signs such as cough and tachypnea. Low-dose steroids are beneficial for asthmalike clinical signs but will not prevent the acute respiratory distress syndrome-like reaction that can occur with the death of an adult worm in the cat. Cats that develop acute, severe respiratory distress may require higher dosages of injectable steroids and oxygen therapy for stabilization.
Bronchodilators (eg, inhaled albuterol) can be prescribed for acute attacks related to bronchial reactivity.
Serial antigen and antibody testing (at intervals of 6–12 months) can be used to monitor status.
Surgical retrieval of heartworms from the right atrium, right ventricle, and vena cavae via jugular venotomy can be attempted in cats in which heartworms are detected by echocardiography. An endoscopic basket, snare, or horsehair brush can also be advanced via the right jugular vein under fluoroscopy. Risks with this procedure include hemorrhage from the venotomy site, tearing/breaking the worms and anaphylaxis (which can be fatal), and damage to the tricuspid valve. Cats in CHF have been cured by heartworm removal.
Treatment of Heartworm Disease in Ferrets
As in cats, heartworm treatment in ferrets is difficult because there is no approved agent for this purpose. Treatment with adulticides (thiacetarsamide and melarsomine) has resulted in a mortality rate in ferrets of approximately 50%. Topical moxidectin and imidacloprid (combination), approved by the FDA for use in ferrets to prevent heartworm infection and to prevent and treat flea infestations, is a logical choice as an adulticidal macrocyclic lactone.
Prevention of Heartworm Disease in Dogs, Cats, and Ferrets
Year-round administration of a macrocyclic lactone preventative is the only way to reliably prevent heartworm infection.
The prevalence of heartworm infection is increasing, and historically nonendemic regions are becoming endemic. In temperate climates, heartworm transmission is seasonal, yet microclimates, temperature fluctuations, and the ability of mosquito larvae to pause and resume their development as temperatures fluctuate complicate knowing exactly when to start and stop the preventative. For this reason, year-round administration is recommended.
An added benefit of continuous administration is that many macrocyclic lactone preventatives are efficacious in preventing other nematode parasites. Dogs traveling to known endemic regions and not receiving a heartworm preventative should have an antigen and microfilaria test; if the result is negative, they should start a macrocyclic lactone preventative before travel. Macrocyclic lactone drugs (ivermectin, milbemycin oxime, moxidectin, and selamectin) target the larval stages of D immitis, preventing the parasite from releasing molecules that help it hide from the host immune system. This allows the host immune system to recognize the parasite as an invader and destroy it. The currently available macrocyclic lactones are highly effective at killing L3 and early L4 heartworm stages.
A diversity of formulations allows monthly topical and oral administration or biannual or annual injectable administration.
Dogs with the MDR1 (ABCB1) gene mutation have deficient activity of the P-glycoprotein drug efflux pump and are at greater risk for toxicosis with certain drugs, including macrocyclic lactones. However, all macrocyclic lactone preventatives are considered safe in dogs with the MDR1 mutation when used at approved dosages.
The use of repellents (eg, permethrin in dogs) and ectoparasiticides such as isoxazolines (afoxolaner, fluralaner, or sarolaner) further decreases D immitis transmission. These drugs should not be used as a stand-alone prevention program but can be used as part of a dual defense strategy against heartworm infection.
Control of the mosquito vector via environmental modifications is also helpful.
Heartworm prevention is also recommended for all cats, especially those in endemic regions, due to the lack of well-studied and effective treatment protocols for heartworm infection. Performing microfilaria testing in cats before starting prophylaxis is recommended but not required, because cats have no or low numbers of microfilariae and their risk for a hypersensitivity reaction is low.
Monthly oral milbemycin oxime; topical moxidectin, selamectin, and eprinomectin; and alternate-month topical moxidectin formulations are available. The commercially available eprinomectin product is labeled for kittens > 7 weeks old, whereas the others are approved for kittens > 6 weeks old.
Although all currently marketed preventatives are likely effective in ferrets, only topical moxidectin/imidacloprid is approved by the FDA. Importantly, the preventive dosage for ferrets is the same as that for dogs, but not cats.
Resistance to Heartworm Treatment in Dogs, Cats, and Ferrets
Macrocyclic lactone–resistant heartworms have been identified; however, their occurrence is still seemingly rare and geographically limited (eg, the Mississippi Delta in the US). All the current molecules used to prevent dirofilariasis have been implicated. However, some formulations (eg, those containing moxidectin) appear to be more effective than others against some currently recognized resistant isolates.
Preventatives are effective in most cases and should not be abandoned. Emphasis should be placed on owner compliance and year-round prophylaxis, as well as on alternative methods of heartworm prevention, including topical and oral mosquito repellent and insecticides; indoor or screened housing, especially at night; and mosquito abatement programs.
If a nonarsenical treatment protocol is unavoidable, it should absolutely be accompanied by 4 weeks of doxycycline administration at the outset, with assurance that microfilariae are eradicated.
Key Points
Heartworm disease is preventable in most instances.
Some form of heartworm adulticide treatment should be offered to all owners of heartworm-infected dogs, other than those with terminal illness or other definite contraindication to treatment.
Although resistance to macrocyclic lactones is an important concern, its immediate threat is limited and localized to the Mississippi Delta region.
Due to the lack of well-studied and effective treatment protocols for heartworm infection, heartworm prevention is recommended in all cats, especially those in endemic regions.
Ferrets are also susceptible to heartworm infection, and treatment is difficult. However, an approved preventive medication is available.
For More Information
References
Romano AE, Saunders AB, Gordon SG, Wesselowski S. Intracardiac heartworms in dogs: clinical and echocardiographic characteristics in 72 cases (2010-2019). J Vet Intern Med. 2021;35(1):88-97. doi:10.1111/jvim.15985
Evaluation of feline heartworm disease based on gross necropsy, serology, pulmonary histopathology, and radiographic evidence in adult shelter cats in northeastern Alabama. Parasit Vectors. 2024;17(1):161. doi:10.1186/s13071-024-06178-9
