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.
Diagnosis
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.
Treatment
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
diagnosis.
• 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…
Prevention
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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