Sunday, July 24, 2011

Notes from July 2011 St. Louis AVMA Conference-Heart Worm Disease

These are papers from the July 2011 St. Louis AVMA conference.  I’ve edited them to delete some of the vet only jargon and for space considerations.  If you see (…) that means that information has been deleted due to these considerations.  The ones listed here include HCM, and other heart related papers, treatments, papers on x-rays and echos, thrombosis, kidney disease, idiopathic cystitis, pain management, anesthesia and cardiac disease, supplements and other hazards for pets, and some other basic information I hope is helpful.

Feline Heartworm Disease Update

Meg M Sleeper VMD, DACVIM (Cardiology)

Associate Professor of Cardiology; University of Pennsylvania School of Veterinary Medicine

Etiology and life cycle

Although dogs are the usual definitive host of Dirofilaria immitis, the life cycle of the parasite

can be completed in cats and feline infection rates in endemic regions are usually 10% to 20%

of that of dogs within the same enzootic region.  It is likely that the morbidity in cats associated

with heartworm disease is underestimated.  Cats are not the definitive host for the parasite and

typically have low and transient microfilarial counts and a longer average pre-patent period

(usually 1-2 months longer) than in dogs. Aberrant migration of the fourth-stage larvae (L4)

occurs more frequently in cats than in dogs. Third-stage larvae (L3) infect the cat via the bite

wound created when an infected mosquito feeds.  Larvae migrate through the subcutaneous

tissues and vascular adventitial tissues.  During this time, 2 molts occur.  Once the larvae enter

the blood stream, they are swept with the circulation to the pulmonary arteries. There is very

high mortality of the young adults (L5) as they reach the feline lungs approximately 3 to 4

months post infection and  only a subset of the larvae ever mature to the adult stage.  Adult

heartworms are typically sexually mature and able to reproduce by 7-8 months post-infection

(which is 1-2 months longer than is seen in the dog).

Prevalence and Pathogenesis

Several studies have shown the heartworm  infection rate in cats is greater than that for FIV or

FeLV. Acute lung injury is the major contributing factor to the initiation of clinical signs.  It is

hypothesized that the arrival of fifth stage larvae in the lungs and the death of adult worms are

the most likely stages of the life-cycle to be associated with clinical signs in the cat.  After an

initial host response, the signs may disappear or become subclinical. D immitis has evolved

various strategies to evade host immune attack and these capabilities could account for the

reduction of clinical signs after the initial, often marked  inflammatory response following arrival

of the L5 stage in the lungs, as well as the acute signs which follow death of the heartworm(s)

in the cat.  Although cats may clear the infection so that no adult worms develop, pulmonary

pathology can still be severe.  Thus, the disease process can be divided  into 3 main stages of

disease in cats, with the first being associated  with the arrival of juvenile worms in the

pulmonary arteries and an acute parenchymal inflammatory reaction.  This stage is followed by

a relatively symptom  free period after the  worms mature to adults and the host immune

response is suppressed.  However, when the worm(s) die, the immune system  is no longer

suppressed and an intense inflammatory response follows (stage 2) with sudden death

reported in 10-20% of affected cats. Finally, if the cat survives, it enters the final stage of

disease with permanent lung injury due to type II alveolar cell hyperplasia and chronic

respiratory disease.

History and clinical signs

The owner of an affected cat may report a wide range of clinical signs such as chronic

coughing, sudden or episodic dyspnea, and/or vomiting.  Vomiting and coughing are common

clinical signs in heartworm  infected cats, and the combination of these signs in a feline patient

warrants a high level of suspicion for heartworm infection.  Lethargy, decreased appetite and/or

weight loss may also be reported.  Occasionally central nervous system signs such as seizures

or blindness may be present, particularly when aberrant migration has occurred.  Asthmatic

signs are common manifestations and often occur about 3 to 4 months post-infection.  In a

subset of cats, severe respiratory distress +/- collapse or sudden death may be the first clinical

sign recognized by the owner…Acute death in affected cats has been attributed to

pulmonary arterial infarction following spontaneous death of adult heartworms; however filariae

are not always present embolizing the main pulmonary arteries and the lung  lobes are rarely

ischemic (based on radioisotope studies…On the other hand, approximately a third of affected cats will

be asymptomatic.


Diagnostic confirmation often requires a combination of tests.  Affected cats usually lack

circulating microfilaria (tests for microfilaremia are positive in less than 20% of infected cats)

and the low worm burdens in this species results in light or absent antigen loads.  Positive

antigen test results are the result of the presence of adult female worms.  In cats, antigen tests

have excellent specificity but false-negative results are common.  False-negative test results

are explained  by low worm  burdens with male-only infections, and infection with young (< 7

month old) female worms that have immature reproductive tracts. The sensitivity of commercial

Ag tests has improved dramatically in recent years and most are effective at detecting a singe

adult female worm.  Heartworm-associated antibody (Ab) tests are useful to rule out infections

in cats when there is an index of suspicion for the disease; however these tests also have

significant limitations.  Because these tests detect exposure to migrating heartworm  larvae,

they may be positive in cats with previous heartworm exposure or infection, so a positive

antibody test indicates exposure but not necessarily active infection.  Previously false negative

results were thought to be rare, but recent studies suggest approximately 14-50% of infected

cats are antibody negative.  Since both L5 larvae and adult worms are capable of causing

clinical disease in the cat, both antibody and antigen tests are useful tools, and the probability

of making appropriate diagnostic decisions improves when they are used together.

Thoracic radiography and/or echocardiography are the two most useful diagnostic tests after

serology in feline patients exhibiting evidence of heartworm disease. The caudal lobar arteries,

especially the right, are the first to enlarge and typically are the most severely diseased… the absence of radiographic abnormalities does not exclude a diagnosis of feline heartworm disease.  In fact, radiographic changes consistent with heartworm disease are noted in only half of the cats suspected to have disease on physical examination.

Echocardiography is a particularly useful adjunctive test in cats in which there is a suspicion of

heartworm disease despite negative Ag test results…The bottom line is that diagnosis of  feline  heartworm disease often requires multiple tests.  

The diagnosis is particularly difficult to confirm in the subset of cats which have stage 1

disease.  In these cats, immature worms may result in severe pulmonary damage, yet be nearly

impossible to diagnose because they are cleared  prior to maturation. Since the antibody

disappears quickly, the only remaining evidence of their presence may be pulmonary lesions

which are virtually impossible to diagnose as caused  by heartworm disease. The syndrome of

vascular, airway and interstitial lung lesions caused by the death of immature worms has been

coined “HARD” or heartworm-associated respiratory disease.


Retrospective studies suggest that 10-20% of cats with adult heartworm infections die

secondary to death of the worm, but adulticide treatment itself is associated with significant risk

in cats, as well.  Infected cats are usually managed with supportive treatment.  Life-long

treatment for chronic bronchial disease may be necessary even after death of all heartworms

in some cats due to residual, chronic pulmonary disease.  Unfortunately, acute death syndrome

may still occur without premonitory signs until all adult worms have died.  It is possible that

therapy with doxycycline will reduce pathology associated with eventual worm death (due to a

reduction in Wolbachia antigens), but studies in cats are still lacking…General treatment

recommendations for heartworm disease in cats:

Treat asthma-like signs with prednisolone (2 mg/kg, daily for 10 days; gradually tapering

to 0.5 mg/kg every other day by two weeks and discontinue in another 2 weeks). Repeat

treatment as needed if recurrent clinical signs occur. Prednisolone is also warranted in cats

without clinical signs if there is radiographic evidence of lung disease.

Consider the addition of a bronchodilator if clinical signs persist despite antiinflammatory

treatment with corticosteroids (i.e. terbutaline, 0.625-1.25 mg/cat PO B-TID;

aminophylline, 4-6 mg/kg PO B-TID; theophylline, 25 mg/kg PO SID; albuterol sulfate

inhaler, 1 actuation BID).

Canine data suggests doxycycline treatment reduces pathology associated with

eventual worm death (due to a reduction in Wolbachia antigens). Although efficacy in cats

remains unclear many clinicians recommend a course of doxycycline at the time of


The monthly use of ivermectin at the prophylactic dose (24 mcg/kg) for 2 years has

been reported to reduce worm burdens by 65% as compared to untreated cats. Therefore,

in cats suspected to have heartworm infection, prophylactic ivermectin therapy is

recommended to both prevent super-infection and to slowly kill the current infection.

However, the inflammatory response to worm  death is likely to occur with ivermectin

treated worm death as well, and therefore owner education is important.

Acute crisis due to a dying worm(s) may require emergent therapy with supportive therapy for

treating shock. Depending on the individual case, this may include:

IV corticosteroids (dexamethasone sodium phosphate, up to 2.2 mg/kg IV or IM)

fluid therapy

bronchodilator therapy (terbutaline, 0.01 mg/kg IV; aminophylline, 4-6 mg/kg IV-inject

slowly; albuterol sulfate inhaler, 1 actuation- Intravenous medications would be preferable

in a dyspneic cat, however in a crisis the owner can administer albuterol with an inhaler

while en route for emergency care)

oxygen supplementation

Diuretics and non-steroidal anti-inflammatory drugs such as aspirin are not

recommended. Studies in cats with heartworm disease have shown only limited benefit to

aspirin therapy at a dose that was approached the feline toxic range.18,19

Use of injectable arsenicals has been associated with fatal thromboembolism or acute lung

injury in cats, and is not recommended. However, surgical removal of heartworms is feasible

and effective in cats with echocardiographically visible filariae in the right heart and/or main

pulmonary arteries.

Monitoring and Prognosis

Periodic monitoring at 6 to 12 month intervals with repeat Ag and Ab testing and thoracic

radiography is warranted. After clearance of adult heartworms (iatrogenic or spontaneous),

infected cats will usually become antigen negative within 4 or 5 months.  However, it is

important to review the results carefully for each  individual case recognizing the inherent

weaknesses of the available tests.  At least regression of radiographic signs and

seroconversion of a positive Ag test suggests the period of risk of an acute crisis following

worm death and embolization is over…


Cat owners should be advised  regarding the potential risk of heartworm  infection in their

community and the comparative ease of preventing the disease vs. the difficulty of treatment.

When monthly heartworm chemoprophylaxis is elected, it should be initiated at least 30 days

following the estimated  seasonal onset of transmission and continued for 30 days after that

period has ended. Year round administration has been recommended by some because: 1)

depending on the product chosen, the cat may also be protected from intestinal or external

parasites, 2) studies suggest owner compliance is better, and 3) there is retroactive efficacy

(“reach back”) if doses are missed inadvertently.  Currently four macrocytic lactone products

are registered for feline heartworm chemoprophylaxis: ivermectin, moxidectin, milbemycin and

selamectin. All of these products are safe and effective options for cats living in areas where

canine heartworm disease is considered endemic and each is administered monthly.

Ivermectin and milbemycin oxime are administered orally while moxidectin and selamectin are

topical. All of these drugs can be safely administered in seropositive cats.

References available from author

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