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It happened in a flash. When Laura McKinnon left for the gym,
“Polo”, a spirited 13 year-old orange and white domestic
shorthaired cat was perfectly fine. When she returned,
Polo was unable to move his rear legs. His owner, Laura
McKinnon, was panicked.
Upon evaluation, Polo was very agitated. His rear legs
were stiff and cold, and no pulses could be detected in
the arteries that supply his rear limbs.
Polo’s clinical signs were very suggestive of a blood
clot disrupting the flow of blood to his rear legs.
Knowing that these blood clots tend to originate from a
larger clot residing within the heart’s left atrium, an
emergency cardiac ultrasound was scheduled for Polo. Not
surprisingly, a large blood clot was indeed detected in
Polo’s left atrium. The ultrasound also revealed Polo’s
primary problem: hypertrophic cardiomyopathy (HCM), the
most common feline heart disorder. Last month, Catnip
subscribers read about HCM and the potential for cats
with HCM to develop a devastating complication called
arterial thromboembolism (ATE). This month, we take a
further look at this serious condition.
Reviewing Hypertrophic Cardiomyopathy
Hypertrophic cardiomyopathy is the most common feline
heart disease seen in clinical practice. In this
condition, the walls of the left ventricle – the heart
chamber responsible for pumping blood out through the
aorta – become progressively thicker. This causes the
chamber size to become reduced, and the ventricle to
become stiffer and less compliant, affecting the
chamber’s ability to fill with blood. This ultimately
affects the heart’s ability to function normally. As a
result, cats with HCM have a guarded prognosis.
There are several potential outcomes for cats with HCM.
Many cats respond well to medical therapy and remain
symptom-free for years. Some cats develop fatal heart
arrhythmias and die suddenly. In some cats, the disease
progresses steadily, ultimately leading to congestive
heart failure. A significant number of cats with HCM
develop aortic thromboembolism. This is one of the most
serious complications associated with hypertrophic
cardiomyopathy (HCM), and is one of the most common
causes of hind limb paralysis in the cat.
The “hows” and the “whys” of ATE
Thrombosis is the formation of a blood clot – called a
“thrombus” – which, in cats with HCM, occurs primarily
within the heart’s left atrium. Aortic thromboembolism
occurs when a piece of this thrombus – called an
“embolus” – breaks free from the main thrombus and
enters the circulation. In some cases, the entire
thrombus breaks free and is carried through the
circulation. The thrombus or embolus eventually becomes
lodged in a vessel, cutting off the blood supply to that
area. Most emboli lodge in the aorta – the biggest
artery in the body – or in one of its major branches.
Smaller emboli may travel into smaller arteries and
affect arterial blood flow to only one limb, or to other
sites such as the brain, lungs, or kidneys. The vast
majority (>90%) of emboli lodge in a spot known as the
aortic trifurcation – the area at the very end of the
aorta where it branches off to supply the left and right
rear legs and the tail. This area has also been called
the “saddle” area, and a blood clot lodged in this area
is commonly called a “saddle thrombus”. Cats are
literally normal one second, and paralyzed in the next
second.
Why do these blood clots form in the first place? In
cats with HCM, the left atrium grows progressively
larger as it tries to send blood into the thickened,
non-compliant left ventricle. As the atrium becomes
dilated, blood flow can become stagnant, increasing the
risk for a blood clot to develop within the atrium.
Blood flow can also become turbulent within the atrium,
and this turbulence can damage to the lining of the
atrium. A blood clot may begin to form at the site of
the damage.
Making the diagnosis
A diagnosis is usually based on clinical signs at
presentation. Most cats present exactly the way Polo
presented: acute onset of lameness, partial paralysis,
or complete paralysis of the affected limbs. Physical
exam often reveals an absence of femoral pulses in both
legs, cold hind limbs, cyanosis (bluish coloration) of
the nail beds and pads, bilateral hind limb paralysis,
hypothermia (low body temperature), and in most cases,
severe pain. Many of the cats with ATE show signs of
shock. Virtually all cats with ATE are in obvious and
considerable pain, as evidenced by excitement, frenzy,
vocalization, rolling, and panting.
Most affected cats are male, although this is probably a
result of the greater predisposition of male cats to
develop HCM. Although any age cat can be affected, the
highest occurrence occurs in cats between four and seven
years old. Certain breeds, including Ragdolls, Birman,
Tonkinese, and Abyssinian, appear to have an increased
risk for development of ATE. Some cats with ATE have
been diagnosed with HCM recently. Others may have been
diagnosed with HCM months or even years before, with no
clinical signs until that day. Some cats with congestive
heart failure that is well-controlled may suddenly fall
victim to ATE. The majority of cats with ATE, however,
present without any evidence of pre-existing heart
disease, just like Polo McKinnon. For these cats,
diagnostic tests such as cardiac ultrasound invariably
confirm that there is heart pathology, and that a blood
clot is indeed present within the left atrium. Today’s
ultrasound machines are able to evaluate arterial blood
flow. During the cardiac evaluation, the ultrasound
probe can be placed on the inside of the thigh to
evaluate arterial blood flow to the rear limbs.
Inability to detect arterial blood flow supports the
diagnosis of ATE.
Initial treatment
The ultimate goal of managing the acute episode of ATE
is to pull the cat through this initial critical phase.
Initially, the focus is on providing rest, controlling
pain, improving cardiac blood flow, and treating CHF if
present. Cats that are in heart failure at the time ATE
strikes may need to be stabilized using oxygen,
vasodilators, and diuretics. Restoring blood flow to the
rear limbs is of secondary importance; making sure the
cat survives takes center stage.
Pain control is essential, as these cats are in great
discomfort. Aspirin, dosed very carefully, can be used
as an analgesic in cats, and may also be beneficial at
inhibiting blood clotting and preventing further clots.
Narcotic pain relievers provide excellent analgesia and
can be safely given to cats with cardiovascular disease.
Improving circulation and perfusion using intravenous
fluids is of paramount importance, however, this can be
a challenge, in that fluid therapy must be administered
cautiously in cats with heart disease.
Acepromazine, a sedative, has been used to decrease
anxiety and improve blood flow to the affected areas by
dilating the blood vessels. No studies have been done to
evaluate the use of this drug in cats with ATE, however,
and its use is still considered to be controversial,
because cats with already low cardiac output run the
risk of having their cardiac output diminished even
further by the use of vasodilators like acepromazine.
Anticoagulants are recommended during the acute crisis.
The goal, in theory, is to prevent any new thrombi from
forming in the heart, and to prevent the embolus from
growing in size and further reducing the blood flow to
the affected region. Anticoagulant therapy is discussed
in more detail below, in the prevention section.
Many cats do not survive the initial episode and they
either die or are euthanized within the first 48 hours
of the onset of paralysis.
Dissolving the clot?
There are drugs available that have the potential to
dissolve a thrombus or embolus. Whether these drugs
offer any real benefit remains controversial. The two
drugs most commonly used are tissue-plasminogen
activator (t-PA) and streptokinase.
TPA is a protein. It is very expensive – one 50 mg vial
costs over $1000. Studies using this drug in cats are
scarce. In one study, about two-thirds of cats given
this drug had perfusion restored to their limbs.
Streptokinase is less expensive. A study of 46 cats with
ATE that were treated with streptokinase showed about
half of the cats had their pulses restored, and 30% had
motor function returned to their limbs within 24 hours.
The side-effects of treating cats with streptokinase or
t-PA make their use questionable. When cats are treated
with thrombolytic (clot dissolving) agents, they become
susceptible to “reperfusion injury” as blood flow is
suddenly restored to the limbs. Electrolyte disturbances
such as hyperkalemia (excessively high potassium levels)
and metabolic acidosis can result, with dire
consequences. In one report of using t-PA to treat cats
with ATE, 70% of fatal complications were due to
metabolic acidosis and hyperkalemia. Hemorrhage can be
another adverse side effect, since these drugs are
designed to dissolve clots.
In the natural course of disease, blood flow will often
resume to the affected area as the body eventually
dissolves the clot on its own. Vessels in the tissues
adjacent to the blocked vessel experience a gradual
increase in blood flow as they learn to adapt to their
injury. In addition, new vessels form, arising from the
embolized vessel. In one large study at the University
of Minnesota Veterinary Medical Center, 45% of cats
survived to be discharged from the hospital with no
therapy to dissolve the clot.
The risk of reperfusion injury, hemorrhage, the
significant cost of the drugs, and the lack of evidence
of improved outcome in cats treated with thrombolytic
agents makes their use questionable, and many
practitioners remain reluctant to administer this form
of therapy.
Removing the clot?
“Rheolytic Thrombectomy” is a technique by which a
special catheter (the “AngioJet” catheter) is used to
remove the clot. A study performed by doctors at the
University of California’s School of Veterinary Medicine
suggests that this technique may hold promise for some
cats with aortic thromboembolism. The study looked at 6
cats that presented with arterial obstruction. Once a
diagnosis of aortic thromboembolism was made, cats were
anesthetized and the AngioJet catheter was inserted and
then threaded down the carotid artery, to the level of
the clot. The clot was then removed using the catheter.
In 5 of the 6 cats studied, the clot was successfully
removed. Three of the 5 cats survived long enough
post-surgery to be discharged from the hospital,
resulting in a survival-to-discharge rate of 50%. The
shortest survival time of the discharged cats was 4
months. The longest survival time was 24 months. The 50%
survival rate compares favorably with survival rates
using other methods, suggesting that this technique
might be a viable alternative for treatment.
Preventing ATE
Preventing ATE is certainly an ideal and logical goal,
however, no studies have been performed in veterinary
medicine, so no therapeutic recommendations can be made
with any scientific support. Over the years,
veterinarians have been only moderately successful at
devising therapeutic protocols that might prevent ATE
from occurring, or from reoccurring. There is no
reliable method to determine which cats with HCM are at
greater risk of developing ATE, although cats that have
been treated with corticosteroids may be at higher risk.
A recent report suggests that cats with HCM that develop
CHF are at higher risk of subsequently developing ATE.
The study also suggests that cats with HCM that undergo
sedation or anesthesia may become at increased risk for
developing ATE. In terms of recurrence, on the basis of
prior reports of cats that have had one ATE episode,
from 25 to 75% may be expected to have another episode.
New drugs, however, may offer some hope in this area.
As discussed above, it is believed that a clot forms in
the heart as a result of blood stagnating in the left
atrium, combined with injury to the lining of the
atrium. When the inside lining of the atrium is damaged,
platelets adhere to the injured area, and the
coagulation cascade begins, leading to the development
of a thrombus or blood clot. Emboli that originate from
the thrombus also contain platelets. Clearly, platelets
play a significant role in the pathogenesis of ATE.
Antiplatelet drugs such as aspirin, therefore, are a
logical choice for prevention of ATE. Aspirin treatment,
however, has not been reported to result in dramatic
reduction in the prevalence of ATE. Recurrence of ATE
has been reported in 75% of cases on aspirin in one
study. Interestingly, a new class of antiplatelet drugs,
the thienopyridines, have been shown to significantly
reduce the risk of stroke and myocardial infarction in
humans, compared with aspirin therapy. One drug in
particular, called clopidogrel (Plavix) is safely used
for this purpose in humans. A recent study in cats has
shown that the drug can be safely administered to cats,
and that it has significant antiplatelet effects. No
adverse side effects were noted. The study wasn’t able
to determine the minimum effective dose, but if used at
the lowest dose used in the study, the cost of the drug
would be approximately $30 a month. The monthly cost
might be even less if it is determined that an even
lower dose was effective. Further studies are needed to
determine the lowest effective dose needed to inhibit
platelets, and more importantly, whether this dose does
in fact reduce the incidence of ATE in cats with HCM.
Fortunately, studies are currently underway to determine
whether aspirin is better than clopidogrel at preventing
further embolic events in cats that survived an initial
episode of ATE.
Warfarin is another drug that may be used as long-term
therapy to prevent further ATE episodes. Warfarin
prevents the synthesis of certain clotting factors. This
inhibits blood clotting, and makes a thrombus less
likely to form. Hemorrhage is a major concern when
instituting warfarin therapy. In fact, it has been
reported that the frequency of fatal hemorrhage in cats
treated with long-term warfarin to prevent blood clots
is 11%. Owners of animals receiving warfarin must be
very committed to their cat’s care and need to monitor
for such signs as bloody stool, blood in the urine, nose
bleeds, pale gums, and bruising.
In people at risk for thromboembolism, low molecular
weight heparin is the current treatment of choice.
Studies in cats are limited, however, there seems to be
a feeling amongst veterinary cardiologists that heparin
might be superior to aspirin or warfarin. Dr. Ross
agrees. “In these cats, some form of clot ‘prevention’
is recommended. Aspirin (81 mg every 3 days) is the
least expensive, but does not prevent all
thromboembolism. In fact, nothing does prevent it 100%,
but low molecular-weight heparin injections given every
day do a better job-- and we generally recommend that in
cats with HCM who seem at high risk for developing
arterial thromboembolism”. Heparin needs to be injected
subcutaneously, in similar fashion to insulin, once or
twice daily by owners. A recent study of the use of low
molecular weight heparin in cats showed that the drug
was easily administered and well tolerated in cats with
cardiac disease. Bleeding complications are infrequent,
and routine coagulation testing in cats may not be
required. The drug is expensive, however, and may exceed
$250 a month if required twice daily. The study,
however, was not able to draw any firm conclusions as to
whether LMWH was able to reduce the frequency of ATE in
cats with HCM. Until further studies are performed, the
fact remains that there is no safe drug with proven
efficacy in preventing ATE.
The prognosis is guarded for cats with HCM that is
complicated by ATE. In a study of 100 cats with ATE, 34%
survived their initial episode. Of those that survived
their initial episode and were released from the
hospital, their average life expectancy was 11 ½ months.
Polo survived his initial episode, however, he never
regained satisfactory use of his rear legs. Despite
medical therapy and aggressive nursing care at home,
Polo’s quality of life continued to deteriorate, and
Polo was euthanized two months after his initial
episode. In early January of this year, Romeo, a sweet
Sphynx belonging to my client Lynn Martin, also
succumbed to ATE. Romeo had been diagnosed with HCM
several months prior. He was stable and doing well,
until stricken with acute hind limb paralysis. Given his
guarded prognosis, Ms. Martin elected to take Romeo home
and try nursing him through his condition. “I turned my
apartment into his very own hospice care clinic. I had
medication, needles, heating pads, special food…
everything. He was here for about 20 hours, and then he
died in my arms”.
The unpredictability of HCM makes it a frustrating
disorder to treat. When ATE strikes cats with HCM, the
frustration factor multiplies by 100. Although there is
no predicting which cats with HCM will be stricken with
ATE, continued research in the areas of prevention and
treatment will allow for more successful management of
this devastating disease in the future.
Glossary
Thrombosis – the formation of a blood clot within the
heart or blood vessels
Thrombus – a blood clot. In this article, it refers to a
blood clot that has formed within the heart.
Embolus – a piece of blood clot that has broken off of
the main thrombus in the heart.
Aorta – the largest artery in the body. It emerges from
the heart and descends alongside the spine, giving off
branches that supply other parts of the body with blood
Aortic trifurcation – the very end of the aorta, where
three branches emerge, one to supply the left leg with
blood, one to supply the right leg, and one to supply
the tail.
Sidebar: clinical signs of ATE
• Acute onset of hind limb paralysis
• Cold rear limbs
• Hard rear limb muscles
• No pulses felt in the rear limbs
• Cyanotic (blue tinged) paw pads and nail beds
• Severe pain
• Low body temperature
• Signs of shock
Updated
7/21/06 |
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