Page 178 - Small Animal Internal Medicine, 6th Edition

150 PART I Cardiovascular System Disorders

with DCM phenotype and CHF. Some of these dogs have Cardiac conduction defects (infranodal AV block and bundle
responded to oral L-carnitine supplementation. branch block), as well as ventricular and supraventricular
VetBooks.ir Prognosis tachyarrhythmias, can also develop with chronic toxicity.
ECG changes do not necessarily precede CHF.
Chronic doxorubicin-induced cardiotoxicity is directly
The prognosis for Boxers with ARVC and normal systolic
function is good with antiarrhythmic treatment. A longitu- related to the cumulative dose of doxorubicin administered.
dinal study showed no difference in life span between Boxers Echocardiographic changes and CHF are generally seen at
2
with and without ARVC (median survival time in both cumulative doses of greater than 150 mg/m , although ECG
2
groups was between 10 and 11 years). In contrast, prognosis changes can be seen at doses as low as 90 mg/m . Cardiotox-
for Boxers with the DCM phenotype form of ARVC is icity becomes particularly likely when cumulative dose of
2
guarded. Most dogs with DCM phenotype progress to CHF, doxorubicin exceeds 240 mg/m . In dogs that have normal
and survival after onset of CHF is generally less than 6 pretreatment cardiac function, clinical cardiotoxicity causing
months. Unfortunately, sudden death remains the most CHF is uncommon, occurring in an estimated 2% to 5% of
common cause of death in dogs with ARVC, regardless of treated dogs. Depending on the underlying neoplastic
LV systolic function, and antiarrhythmic treatment may process (e.g., hemangiosarcoma), dogs may not live long
ameliorate but does not eliminate this risk. enough to experience chronic toxicity from doxorubicin
treatment. Although predicting whether and when clinical
ARRHYTHMOGENIC RIGHT cardiotoxicity will occur is difficult, dogs with underlying
VENTRICULAR CARDIOMYOPATHY IN cardiac abnormalities and those of breeds with a higher
DOGS OF OTHER BREEDS prevalence of idiopathic myocardial disease (e.g., Dober-
A form of cardiomyopathy that mainly affects the RV has mans, Great Danes, Boxers) are thought to be at higher risk.
been observed rarely in English Bulldogs and other breeds. Echocardiography and ECG are used to diagnose doxo-
It appears similar to ARVC described in people and cats. rubicin cardiotoxocity. Increases in circulating cardiac tro-
Pathologic changes are characterized by widespread fibrous ponin concentrations can also be seen. However, no screening
and fatty tissue replacement in the RV myocardium. Marked modalities (biomarkers or imaging) have proven effective in
right heart dilation is typical. In certain geographic areas, predicting future cardiotoxicity. Whether and how frequently
trypanosomiasis is a possible differential diagnosis. Clinical to screen dogs for cardiotoxicity during treatment depends
manifestations are largely related to right-sided CHF and on multiple factors, including breed, presence of preexisting
severe ventricular tachyarrhythmias; sudden death is a heart disease, underlying neoplastic disease, and relative risk
potential outcome. aversion of the oncologist and owner.
Various strategies have been employed in an attempt to
decrease risk of cardiotoxicity with doxorubicin administra-
SECONDARY MYOCARDIAL DISEASE tion. In humans, giving doxorubicin as a prolonged continu-
ous infusion (at least 6 hours) decreases drug toxicity; there
Poor myocardial function can result from a variety of iden- is some evidence that in dogs, administering the drug diluted
tifiable insults and nutritional deficiencies. Myocardial infec- (0.5 mg/mL) over 1 hour may similarly decrease risk. Con-
tions (see p. 153), inflammation, trauma (see p. 155), current administration of the iron chelator dexrazoxane
ischemia, neoplastic infiltration, and metabolic abnormali- (Zinecard) prevents doxorubicin-induced lipid peroxidation
ties can impair normal contractile function. Hyperthermia, and might also decrease risk of toxicity. However, application
irradiation, electric shock, certain drugs, and other insults to veterinary medicine is somewhat limited due to expense
can also damage the myocardium. Some substances are of this drug. Other attempts have involved use of pegylated
known cardiac toxins. liposome-encapsulated doxorubicin or concurrent adminis-
tration of antioxidants such as carvedilol or vitamin E and
MYOCARDIAL TOXINS selenium.
Doxorubicin Other toxins
The antineoplastic drug doxorubicin induces both acute Ethyl alcohol, especially if given IV for the treatment of
and chronic cardiotoxicity. Release of histamine with sec- ethylene glycol intoxication, can cause severe myocardial
ondary catecholamine release appears to underlie acute tox- depression and death; slow administration of a diluted
icity, which is idiosyncratic and leads to transient ventricular (≤20%) solution is advised. Other cardiac toxins include
or supraventricular arrhythmias during drug administra- plant toxins (e.g., Taxus, foxglove, black locust, buttercups,
tion. Chronic cardiotoxicity appears to be mediated by DNA lily-of-the-valley, gossypol); anesthetic drugs; catechol-
intercalation, inhibition of topoisomerase II, and free-radical amines (including the feed additive ractopamine); and iono-
production. The resulting myocardial damage is character- phores such as monensin. Other potential cardiac toxins
ized histologically by vacuolization and degeneration of car- recognized in humans include heavy metals (e.g., arsenic,
diomyocytes. Chronically, cellular toxicity leads to LV lead, mercury); antineoplastic drugs (cyclophosphamide,
dilation and decreased LV systolic function, mimicking idio- 5-fluorouracil, interleukin-2, α-interferon); other drugs
pathic DCM. Left-sided CHF is the eventual clinical outcome. (e.g., thyroid hormone, cocaine, amphetamines, lithium);