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Cani ne He ar t wor m Di s e as e

Matthew W. Miller, DVM, MS, DACVIM (Cardiology)

efore discussing therapeutic strategies for treatment of
dogs with severe heartworm disease i t is necessary to
establish criteria that define severe heartworm disease. Until
recently an organized grading scheme has not been available
for standardized categorization of dogs with heartworm dis-
ease. A clinical clasmflcation scheme has been put forth in an
attempt to facilitate communication between clinicians and
add some degree of objectivity to the comparison of therapeu-
tic interventions. This classification scheme categorizes dogs
based on subjective and objective parameters into those with
subclinical (mild), moderate, and severe disease. 1 The major
parameters used to categorize dogs are listed in Table 1. This
article will emphasize management strategies for those dogs
considered to have severe heartworm disease.
Although caval syndrome is most certainly a form of severe
heartworm disease we will not consider in detail the surgical
management of caval syndrome. Many of the concepts outlined
in this manuscript, however, are applicable to the therapy of
dogs with caval syndrome after surgical reduction of worm
burden. Please refer to the manuscript in this issue which deals
specifically with this topic. 2,3 The therapeutic strategy for dogs
with severe heartworm disease can be divided into several
stages: initial stabilization, adulticide therapy, management of
thromboembolic disease and evaluation of the efficacy of
adulticide therapy. Table 2 provides an outline of the medica-
tions commonly employed in the management of dogs with
severe heartworm disease.
Initial Stabilization
Eosinophilic Pneumonitis
Eosinophilic pneumonitis is manifested as an intense eosino-
philic pulmonary parenchymal infiltrate that develops in
response to the presence of adult heartworms (dead or alive) in
the pulmonary arteries. Radiographically this appears as dif-
fuse bronchointerstitial parenchymal infiltrate (Fig 1). It often
causes tachypnea, shortness of breath and cough. Eosinophilic
pneumonitis is usually very responsive to corticosteroid therapy
with chnical and radiographic improvement commonly seen 2
to 5 days following initiation of therapy. Once clinical response
has been noted the dose of corticosteroid should be gradually
tapered. Adulticide therapy should be instituted as soon as
possible after resolution of clinical signs.
From Texas A & M University, College Station, TX.
Address reprint requests to Matthew W. Miller, DVM, MS, DACVIM
(Cardiology), Associate Professor, Texas A & M University, C o l l e g e
Station, TX 77483-4474
Copyright 1998 by W.B. Saunders Company
Clinical Techniques in Small Animal Practice, Vol 13, No 2 (May), 1998 pp
Pulmonary Hypertension and Congestive Heart Failure
Signs of congestive heart failure are most commonly associated
with severe pulmonary hypertension. Evidence of long stand-
ing disease with pulmonary hypertension is readily seen with
thoracic radiographs (Fig 2). Myointimal proliferation, villous
endarteritis, thromboembolism, reactive pulmonary vasocon-
striction secondary to alveolar hypoxia and to a much lesser
extent, physical obstruction from the adult worms a l l play a
role in the pathogenesis of pulmonary hypertension. Strict cage
rest is the cornerstone of the management of these patients.
Numerous studies have documented the dramatic affects of
even mild physical activity on pulmonary hemodynamics. 4,5
There is little that can be done to address many of the factors
that contribute to elevated pulmonary vascular pressures and
ultimately pulmonary hypertension. The inflammatory vascu-
lar changes and the physical presence of worms respond only
to worm elimination and time. Administration of vasodilating
drugs may be associated with some reduction in pulmonary
vascular resistance. It is important to remember that the
pulmonary vasculature is markedly abnormal in these patients
and, therefore, would not be expected to respond normally to
vasodilating drugs. 6 Peripheral vascular dilation may be much
more dramatic than the degree of pulmonary vascular dilation.
This can result in marked reductions in systemic blood
pressure with minimal benefit with regards to pulmonary
vascular pressure.
Most successful management strategies are directed at im-
proving alveolar oxygenation with resultant pulmonary vasodi-
lation. 6 Supplemental oxygen admimstration is the most expe-
dient way to affect this type of response. Corticosteroid therapy
may Improve alveolar oxygenation indirectly by reducing
pulmonary inflammation. Administration of bronchodilators
(TheoDur [Schering-Plough, Kenilworth, NJ] 10 mg/kg by
mouth twice daily) may improve alveolar oxygenauon through
elimination of bronchocorlstriction commonly associated with
pulmonary inflammation. In dogs with severe arterial changes
and pulmonary parenchymal infiltrate, supplemental oxygen
therapy may yield dramatic clinical results.
Most dogs with severe pulmonary hypertension have signs
attributable either to decreased cardiac output (weakness,
exercise intolerance, collapse) or elevated venous pressure and
congestion causing ascites with or without concurrent pleural
effusion. Aggressive use of diuretics should be avoided if at all
possible in these patients. Administration of high-dose diuret-
ics typically causes reductions in circulating plasma volume
and reductions in cardiac output. If patients have overt signs of
respiratory compromise secondary to substantial amounts of
pleural or abdominal effusion accumulation physical removal
is much more beneficial and associated with minimal complica-
tion. Medical management of right-sided congestive heart
failure should be directed at augmenting cardiac output by
optimizing heart rate augmenting myocardial contractility and
113-118 1 1 3
T ABL E 1. Pa r a me t e r s Used t o Cl assi f y Sever i t y of He a r t wor m Di sease
Parameter Class 1--Subclinical Class 2--Moderat e Class 3---Severe
Parasitologlc Diagnosis Negative or "weak" positive result on Positive result on test for HW Ag
semlquantitative test for HW Ag Knott test may be positive or negative
If Ag test negative: positive Knott test
History No clinical signs
Physical Examination
Thoracic Radiography
Good general condition
Mild to moderate exercise intolerance
Occasional cough with exercise
Good/Fair general condition
Normal Normal
+ / - Evidence of RVH
Normal cardiac silhouette; + / - mildly
enlarged pulmonary arteries; + / -
mild pulmonary parenchymal infil-
Laboratory Data Normal
Moderate enlargement of the nght ven-
tricle and main pulmonary artery;
moderate enlargement of the caudal
pulmonary arteries with evidence of
truncation and tortuosity; diffuse
perlvascular parenchymal infiltrates
+ / - moderate anemia (PCV 20-30%)
Mild to moderate protelnuria common
Prognosis Good Good/Fair
Positive test for circulating HW Ag;
Usually highly positive when using a
semiquantltative test
Knott test may be positive or negative
Marked exercise intolerance, weight
Increased respiratory rate at rest, per-
sistent cough
Fair to poor general condition; evi-
dence of right heart failure: (ascites,
jugular venous distention)
Right ventricular hypertrophy
Right axis shift or RBBB
Arrhythmias (VPC, A. Fib.)
Right ventricular and right atrial
Enlarged main pulmonary artery;
enlarged, tortuous and truncated
lobar pulmonary arteries; diffuse
perlvascular pulmonary paren-
chymal infiltrates with evidence of
Anemia common (PCV <20%)
Significant elevations in hepatic
enzymes and/or BUN and creatlnine;
moderate to severe proteinuna
Overlap between categories is common. All abnormalities need not be present to assign a patient to a given category. Classification of older dogs and
dogs weighing less than 10 kg should be biased toward the higher class. It should be emphasized that these s~mply represent guidelines for classification.
RVH = right ventncular hypertrophy; HW Ag = heartworm antigen; RBBB = right bundle branch block; VPC = ventncular premature complex; A. Fib. =
atrial fibrillation; PTE = pulmonary thromboembolism.
T ABL E 2. Dr ugs C o mmo n l y Used t o Tr eat Se v e r e He a r t wor m Di sease
Intervention Indication Dosage Complications
Prednisolone PTE
Eosinophihc pneumonltis
Heparin PTE prevention and therapy of DIC
Melarsomlne HCI Adultlclde
Thiacetarsamide Adultic~de
Supplemental oxygen
Pulmonary hypertension
Pulmonary hypertension, CHF
Pulmonary hypertension, CHF
Heart failure, supraventrlcular tachyar-
Furosemlde:l: CHF
Aspirin PTE
1-2 mg/kg divided PO BID taper fol-
lowing clinical response
50-100 IU/kg SQ TID or dose sufficient
to increase APTT to 1.5 to 2.0 times
baseline, start 2 weeks prior to adulti-
clde therapy and continue as long as 4
weeks after completion
2.5 mg/kg IM 2 injections 24 hours apart
or 1 rejection followed ->30 days later
by 2 injections 24 hours apart
2.2 mg/kg IV, 2 injections per day for two
consecutive days, 8 hours between
injections on the same day, no more
than 15 hours between injections 3
and 4
40% FiO2 via nasal insufflatlon or cage
0.5 mg/kg PO initial dose tltrated to
0.5-2.0 mg/kg PO BID
1 0-1.5 mg/kg PO TID
0 22 mg/M 2 PO BID or 0 005-0.01 mg/kg
0 5-2 0 mg/kg PO SID-TID
3-10 mg/kg PO SID
Potential to decrease adult worm kill, GI
Spontaneous hemorrhage
Mild, local celluhtis, excessive salivation
PTE following worm death
Severe celluhtls associated with extrava-
satlon, acute hepatic and/or renal dys-
function; PTE following adult worm
Long-term exposure to 100% FIO2 may
cause lung injury
Systemic hypotension
GI anorexia, vomiting
Systemic hypotension
GI: anorexia, vomiting
Cardiac: ventricular arrhythmlas, brad-
Hypovolemla, electrolyte and acid/base
GI ulceration
*Data regarding the response to vasodllators is sparse and somewhat conflicting; mdw~dual variation is marked and caution should be taken not to cause
systemic hypotension. This is especially important when using these drugs in combination with a diuretic.
1-The efficacy of d~goxin in severe heartworm disease ~s controversial, conservative dosing with frequent monltonng of serum dlgox~n levels ~s prudent, if
ascites is present an estimate of patient weight without ascltes should be the basis for dosing.
:~High doses of diuretic should be avoided.
The American Heartworm Society does not recommend the routine use of aspirin in dogs with heartworm disease. CHF = congestive heart failure;
PTE = pulmonary thromboembollsm; M = body surface area ~n meter squared; DIC = disseminated intravascular coagulation
Fig 1. Lateral thoracic radiograph from a dog with eosinophilic pneumonitis associated with heartworm disease. Notice the
intense and diffuse nature of the bronchointerstitial infiltrate. The pattern of infiltration may take several radiographic forms
and may appear nodular as well. The pneumonitis associated with heartworm disease is typically quite steroid responsive.
reducing afterload (reducing the severity of pulmonary hyper-
tension). The clinical efficacy of medications including di-
goxin, diuretics, Angiotension converting enzyme inhibitors
(ACEI) and the vasodllators hydralazine and &ltiazem is
variable and poorly described. 6 The effectiveness of conserva-
tive management (strict cage confinement, moderate dietary
sodium restriction, and supplemental oxygen) should not be
Adulticide Therapy
IMMITICIDE [Merial Limited, Isehn, NJ] (Melarsomine hydro-
chloride) has been shown to be more efficacious and safer than
sodium thiacetarsamide. 7,8 This is especially true in the setting
of severe heartworm disease where a staged reduction in worm
burden may be desired. Results of both clinical and laboratory
investigations suggest that a split dosing regimen (see Table 2)
allows for a staged worm kill. This drug is currently the
adulticide of choice for the therapy of heartworm disease in
dogs and is an especially welcome alternative to sodium
thiacetarsamide in this subset of dogs.
The chemotherapeutic agent sodium thiacetarsamlde is still
occasionally used for the elimination of adult heartworms In
dogs. The therapeutic regimen recommended by the American
Heartworm Society is 2.2 mg/kg IV twice daily for 2 consecu-
tive days. Using an increased dose (2.64 mg/kg/injection) is not
recommended because a rapid, more complete adult worm kill
in patients with severe disease may result in life-threatening
pulmonary embolic disease. Clinical trials suggest that reduc-
tion of worm numbers, even without complete elimination of
adult worms, frequently results in significant clinical improve-
ment. r The goal of initial adulticide therapy should be to
reduce the worm burden with improvement in clinical signs.
Much has been written about the affects of corticosteroid
therapy on the aduhicidal efficacy of thiacetarsamide. 9 Stud-
ies have suggested that steroid therapy prior to adulticide
therapy will protect the worms and decrease worm kill. 9 This
can be viewed in two ways. First, the data to support this
assertion are not nearly as strong as the fervor with which the
statement has been perpetuated. Second, if prior corticoster-
oid therapy decreases worm adult kill; is that necessarily a
bad thing in patients with severe heartworm disease? Would it
not be advantageous to kill a portion of the adult worms and
obtain some clinical benefit? After administration of adulticide
therapy, reinfection could be prevented with the use of
appropriate chemoprophylaxis and aduhicide therapy repeated
at a later date if necessary. Corticosteroids do not appear to
have any adverse effects on the adultictde efficacy of Immiti-
cide.7, 8
Recent experimental evidence has confirmed the long held
clinical suspicion that the HEARTGARD Plus Chewables
[Medal Limited, Iselin, NJ] product containing ivermectin and
pyrantel has important adulticidal activity. McCall et al re-
ported that administration of HEARTGARD Plus Chewables
(administered to provide 6 l~g/kg of ivermectin and 5 mg/kg of
pyrantel) for 16 consecutive months provided an incomplete
but significant reduction in worm counts relative to untreated
in worm mass may be accomphshed surgmally, chemotherapy
to eliminate remaining worms is commonly required and still
presents a sigmficant risk (pulmonary thromboembolism) to
the patient.
Fig 2. Ventrodorsal thoracic radiograph from a dog with
severe heartworm disease and pulmonary hypertension.
Notice the dramatic right ventricular enlargement manifested
as rounding of the right heart border and the classic "re-
versed-D" appearance of the cardiac silhouette. The dramatic
dilation and tortuosity of the caudal pulmonary arteries is
strong evidence of pulmonary hypertension. Pulmonary hy-
pertension can be documented noninvasively with Doppler
echocardiography (see manuscript on caval syndrome).
controls and to dogs treated with INTERCEPTOR [Novartis
Animal Health] (administered to achieve a dose of 500
pg/kg).I0 Although several people have suggested that this may
be the ideal way to manage dogs with severe disease there is
currently little evidence to support that claim. Decisions as to
whether or not dogs with severe &sease should receive
conventional adulticide therapy should take into account the
perceived benefits of an exceptionally slow adult worm kill and
the potential for progressive pulmonary vascular and parenchy-
mal injury. The exact amount of time over which the worms die
is unknown.
Surgical Removal
In cases of caval syndrome, surgical removal of worms using an
endoscopm basket retrieval device or alligator forceps may
result in significant clinical improvement. While the surgical
approach to caval syndrome is widely accepted, surgical
management of dogs with heavy adult worm burdens without
signs typical of caval syndrome is less well estabhshed (Figs 3A
and 3B). A recent study demonstrated that percutaneous
removal of worms from the pulmonary arteries using a flexible
alligator forcep was beneficial in heavily parasitized animals
without signs of caval syndrome or congestive heart failure. 11
In this study it should be emphasized that although reductmn
Fig 3. (A) Right parasternal short axis view showing the
bifurcation of the pulmonary arteries. The hyperechoic struc-
tures within the lumen are adult heartworms. This patient
presented for progressive weakness followed by collapse.
(B) Necropsy specimen from the patient in figure 3A. Notice
the large mass of worms within the opened main pulmonary
Fig 4, (A) Lateral thoracic radiograph from a dog with heart-
worm disease. There are minimal changes typical of heart-
worm disease, Since this patient was clinically normal it
would be assigned to Class 1 disease status, (B) The same
patient 10 days following adulticide therapy. Notice the
diffuse interstitial and alveolar pulmonary infiltrate typical of
severe embolic disease.
Thromboembolic Disease
Although local celluhtis and acute hepatic or renal toxicity
occasionally occur (renal and hepatic toxicity are very uncom-
mon with Immiticide), the most serious complication follow-
ing aduhicide therapy is thromboembolic disease. Several
studies have addressed the topic of thromboembolic &sease yet
ideal therapy remains elusive. There is good evidence that the
subcutaneous administration of heparin can reduce the sever-
lty of thromboembolic disease in dogs with heartworm &sease.
In dogs with severe heartworm disease it has been suggested
that heparin administration begin as early as 2 weeks prior to
aduhicide therapy and continue for 2 to 6 weeks after
completion. 12 Dogs presenting with clinical signs of severe
pulmonary embolic disease (shortness of breath, hemoptysis,
cyanosis) require aggressive supportive care (Figs 4A and 4B).
Strict cage confinement administration of supplemental oxy-
gen and cautious fluid therapy are indicated. Heparin therapy
should be instituted to combat ongoing pulmonary embolism
and for potential beneficial affects on the clinical progression
of disseminated intravascular coagulopathy (DIC). The admin-
istration of warfarin derivatives or clot lysing agents requires
intensive monitoring capabilities and is assocmted with severe
potential complications, most notably spontaneous hemor-
rhage (Fig 5). The use of diuretics, anubiotics, and bronchodi-
lators is somewhat controversial.
Evaluation of Adulticide Therapy
A serologic test for circulating adult heartworm antigen should
be performed 5 to 6 months after adulticide therapy. Although
some dogs will seroconvert within 12 to 16 weeks of comple-
tion of adulticide therapy, a small percentage will not convert
for as many as 20 weeks or longer/13,14 Also, if a posiuve test is
obtained and the decision to repeat adulticide therapy is made
it would be ideal to walt at least 6 months from the time of the
first therapy. The adult worms that were not killed during the
first adultlclde therapy were most likely immature females,
perhaps made more resistant by exposure to corticosteroids
(this would only be true if thiacetarsemide was used as the
adulticide). If the dog is receiving appropriate chemoprophy-
laxis between the ume of initial aduhicide therapy and the
decision to repeat therapy, reinfection is extremely unlikely.
Clinical improvement associated with reduction of worm mass
will make the repeated use of corticosterolds unnecessary. The
worms that survived the first regimen of adulticide therapy
should be fully mature by the time the decision to repeat
aduhlcide therapy is made and therefore the chance of com-
plete elimination of adults is maximized by using this regimen.
The decision to repeat aduhicide therapy should be made on an
individual basis taking into account client expectations in
addition to patient parameters including age, concomitant
problems, complications with the initial therapy and clinical
con&tion. There is an important distinction between heart-
worm disease and heartworm infection.
Fig 5. Necropsy specimen from a dog with heartworm dis-
ease that died suddenly, A large thrombus is present in the
pulmonary artery. Mature thrombi such as this typically do
not respond to thrombolytic therapy. Therapeutic measures
should include attempts to slow progression of clot expan-
sion and promote collateral circulation.
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worm disease classification, serum antigen concentration, and associ-
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Heartworm Symposium 1995
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advances Proc Heartworm Symp 1989 27-31, 1989
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dysfunchon m an experimental model of heartworm caval syndrome in
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of dogs following heartworm adultlclde treatment with melarsomlne.
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