Systemic arterial embolism (SAE) is one of the more tragic syndromes affecting cats. The vast majority of affected cats have concomitant cardiac disease, although occasional affected cats have minimal or no identifiable heart disease and no other obvious cause for SAE. Neoplasia, particularly pulmonary angioinvasive adenocarcinoma, may be associated with SAE. The cardiac findings associated with SAE are most often hypertrophic cardiomyopathy (HCM) and an enlarged left atrium (with HCM or other cardiomyopathy). The size of the left atrium (LA) is probably proportional to the risk of development of SAE. Because of this and the fact that thrombi are occasionally "visualized" by echocardiography in the LA, this chamber is considered to be the source of SAE. Males are predisposed to both HCM and SAE.

Pathogenesis

The postulated pathogenesis of LA thrombi invokes the sluggish blood flow in this dilated chamber in which activated clotting factors re-circulate in eddying blood. This hypothesis is supported by the fact that SAE less commonly complicates hyperthyroidism, a high-output form of cardiac disease. This sluggish flow of blood and endothelial damage associated with mitral regurgitation (jet lesion) and/or the underlying heart disease (both of which reveal collagen to which platelets adhere) allow the genesis of thrombi. It is believed that these thrombi or fragments of these thrombi are released, lodging most commonly (at least from a clinical perspective) in the distal aorta at the origination of the iliac arteries (saddle thrombus). In actuality, the most frequent site in the author's experience is the kidney, which upon necropsy is often shown to have multiple small (clinically silent) infarcts in cats with saddle thrombi. Other sites for SAE include the abdominal or proximal aorta and the coronary, mesenteric, brachial and cerebral arteries. While the brachial artery location is associated with a better (guarded to good) prognosis, the remainder of these alternative SAE sites are typically associated with a fatal outcome.

Physical Examination & Diagnosis

SAE is typically associated with an acute or peracute presentation, usually with rear limb paralysis/paresis. Classical findings include posterior limb pain, lack of pulse, gradual (over days) hardening of the gastrocnemius and quadriceps muscles, lack of pulse and pale/cyanotic foot pads or nail beds, the latter not bleeding upon quicking. If SAE is partial, a pulse (weak or even normal unilaterally) may be detected, carrying a better prognosis. If the attending clinician cannot ascertain with certainty whether SAE is present, Doppler technology (Doppler diagnostic ultrasound or blood pressure monitoring equipment) or non-selective angiography may be used to confirm the diagnosis.

Typically, a murmur or gallop is noted--interestingly, the majority of affected cats have no prior history of heart disease. Sinus tachycardia is typical and may be complicated by arrhythmias (APC or VPC). Heart rate may be deceptively low if hypothermia is present. When SAE affects alternative sites, the signs may range from sudden death (coronary or cerebral arteries or proximal aorta) to an acute abdomen (aorta at level of kidneys or mesenteric arteries) or to front leg lameness. When affected, the kidneys can be isolated and are firm and quite painful to palpation. Often (approximately 50% of reported cases) heart failure (CHF) complicates SAE, probably because of the associated stress/pain and SNS activation. These cats demonstrate dyspnea (acute pulmonary edema most commonly) in addition to other aforementioned signs. Chronic complications may include contracture and necrosis, the latter requiring amputation in some cases.

Treatment

Attempts at "clot-busting" have given inconsistent, often tragic (reperfusion syndrome or hemorrhage), results. For that reason, the author does not utilize these therapies (streptokinase, tissue plasminogen activator [t-PA]). Surgery, while potentially useful in very early SAE, has fallen into disfavor. Treatment is therefore aimed at supporting and comforting the patient, stopping/slowing thrombus growth and further emboli formation, blocking vasoconstriction and allowing recanalization and revascularization to occur. Specifically, acute treatment includes warming (if needed), pain control/sedation, anticoagulation, and treatment of CHF, as needed. Later, passive physical therapy is applied in an effort to prevent contracture.

The ideal treatment/prevention of SAE is not agreed upon. Part of the confusion lies in controversial data from small, typically retrospective, clinical studies or data from normal cats. I will not explore these controversies but will advise the reader as to what I do and recommend.

When an owner or referring veterinarian calls and describes clinical signs compatible with acute SAE, this author advises that the cat be given a baby aspirin (81 mg) or ¼ adult aspirin and brought post-haste to the NCSU CVM or referring veterinarian, whichever is nearer. Early treatment, though not supported by confirmatory data, is thought to be of paramount importance. Upon arrival, treatment might include Lasix, IV or IM, nitroglycerin topically, and oxygen therapy for CHF patients. This treatment is typically adequate for HCM patients, with addition of lusitropic agent(s), namely, beta- and/or calcium channel-blockers, in 24-48 hours in most cases. The beta-blocker propranolol is contraindicated in SAE because of its B₂-blocking (vasoconstrictive) properties. At the time of admission, anticoagulation is begun with dalteparin (low molecular weight heparin )100 u/kg SQ daily, Fragmin^R) SQ once daily. Additionally, if not administered earlier by owner or referring DVM, 81mg aspirin (to impair platelet adhesion and growth of thromboembolus and to block release of platelet-derived vasoconstrictors--thromboxane A₂ and serotonin) is given once. If financial concerns will ultimately prevent the chronic use of dalteparin, I use instead, unfractionated heparin, SQ at 250-300 units/kg tid, with our without monitoring APPT during the hospital stay. Pain control is achieved (buprenorphine @ .01 mg/kg IV, SQ, or PO [buccally] or with another opiate) and, as needed for persisting hypothermia, heat is provided with a warm water blanket. If tolerated, a warm, water-filled exam glove is placed between the rear legs for heat and to improve circulation. Other nursing/supportive care might include fluid therapy (cautiously, especially if patient has experienced CHF) using formulations poor in sodium (e.g., Plasmalyte 56^R or 50:50 0.45% saline and 2.5% dextrose with potassium added when appropriate, based on clinical findings), ensuring adequate caloric intake, care of ulcerated wounds in chronic cases, and cleaning and care of paralyzed limbs. Care should be taken not to apply ECG electrodes to ischemic limbs as the tape or elastic wrap necessary to ensure contact with prolonged monitoring may worsen the ischemia.

Other potential therapies, typically not used in this situation at NCSU, are aimed at dilating vasoconstricted collateral arteries and arterioles. These drugs include vasodilators (diltiazem [7.5 mg PO tid], amlodipine [0.625-1.25 mg once daily], hydralazine [2.5 mg PO once daily to bid] or acepromazine [0.02-0.03 mg/kg SQ PRN to end-point of mild sedation]) and cyproheptadine (2-4 mg once daily to bid) to block serotonin-induced vasoconstriction. The latter drug has been shown to be effective in experimental SAE when administered prior to aortic occlusion, but is not believed to be useful after the event. My logic in the use of this drug is that it has theoretical benefit in maximizing collateral circulation as long as serotonin is being released from platelets and is an appetite stimulant as well. Other vasodilators should be used with caution because resultant hypotension will worsen the results of ischemia and reduced afterload in cats with HOCM (hypertensive obstructive cardiomyopathy) has the potential to worsen outflow obstruction and to reduce cardiac output. Finally, there is no proof of efficacy for these drugs.

Prognosis

Euthanasia is a reasonable option for cats with SAE, particularly if there are financial constraints, if CHF complicates the syndrome, or if negative prognostic indicators are noted (e.g., rock-hard legs or hypothermia). Other negative prognostic indicators (Smith, et al. 2003) include rectal temperature <96.5⁰F (<25% of cats so-affected are released from hospital), slower heart rate [mean 188bpm vs 210bpm for "survivors"], lack of motor function, multiple sites affected, and hyperphosphatemia. It is my opinion that every client whose cat suffers SAE should be offered euthanasia as an option. In one retrospective study (Schoeman, 1999) 39% of SAE cats were released from the hospital while 28% died and 33% were euthanized. Overall, the prognosis for SAE is grim, with most studies reporting a release from hospital of <50% of SAE cases, a median survival of ~50-250 days, a recurrence rate of ~25-75%, and treatment-related deaths of ~10-20% (Smith SA and Tobias, 2004; Smith, CE, et al., 2004). On a more optimistic note, the NCSU experience with dalteparin suggests the possibility of a more promising outcome. This cautious optimism is supported by data from Tufts University which showed only a 15% recurrence rate in dalteparin-treated cats and a very low incidence of adverse side-effects (Smith, CE, et al. 2004). We have also experienced post-SAE survival years in duration with dalteparin treatment, some of which have occurred in amputees.

Prevention

The cautious optimism displayed above carries over to prevention, as well. There again is no consensus among veterinary cardiologists as to the best (or any) method for preventing SAE. Aspirin has never been proven to prevent SAE, nor has it been studied in this regard. It is known that aspirin at 81 mg/72h effectively disables platelets in normal cats. Recently, a retrospective study showed no difference between 81 and 5 mg/72h in terms of SAE development and survival (Smith SA and Tobias, 2004). In lieu of an actual prospective clinical trial, this author uses aspirin at 40 mg/72h for cats <4kg and 81 mg/72h for cats >4kg which have no history of SAE and whose LA (2-D long-axis view) is 1.6-2.0 cm in diameter. If signs of gastric distress are noted (vomiting or anorexia), the dosage is halved or the drug discontinued. More aggressive anticoagulation is chosen if the LA is > 2.0 cm, if there is a history of SAE, if a murally-attached thrombus (a free-floating LA thrombus is a death knell--if pharmacologically reduced in size, it will likely lodge in the left ventricular outflow tract or aorta, producing catastrophic results) is identified in the LA, or if spontaneous echo contrast ("smoke") is visualized in the LA. My preference for aggressive anticoagulation is dalteparin at 100 units/kg SQ daily (>$100/month for adult cat). At NCSU, if SAE develops in cats on dalteparin or if the patient is judged to be at very high risk, aspirin may be added to the dalteparin treatment regimen. Our experience with dalteparin suggests benefit when current patients are compared to historical controls and efficacy equal to that of warfarin (with less cost and risk). If cost is a factor, 18.75 mg/day clopidogrel (Plavix^R; Hogan, D, et al. J Am Vet Med Assoc, 2005) is substituted for dalteparin. There is no proof of clopidogrel's efficacy in cats, though this drug has been shown to be safe in cats and the benefit/risk ratio in humans is favorable. No monitoring of coagulation function is performed with any of these drugs. The use of warfarin is avoided because of the difficulties in its use, cost and frustration of monitoring PTT, and frequency of hemorrhagic complications.

Cardiovascular formulary for cats.

*Selected name brands; some available as generic.
**Most appropriate formulations for cats--other sizes available for many drugs.

References

1.  Smith SA, Tobias AH, Jacob KA, et al. Arterial thromboembolism in cats: Acute crisis in 127 cases (1992-2001) and long-term management with low-dose aspirin in 24 cases. J Vet Intern Med 2003; 17:73-83.

2.  Smith SA, Tobias AH. Feline arterial thromboembolism: an update. Vet Clin SA Pract 2004; 34:1245-1271.

3.  Moore KE, Morris N, Dhupa N, et al. Retrospective study of streptokinase administration in 46 cats with arterial thromboembolism. J Vet Emerg Crit Care 2000; 10:245-247.

4.  Smith CE, Rozankski, Freeman LM, et al. Use of low molecular weight heparin in cats: 57 cases (1999-2003).

5.  Hogan D, Andrews DA, Green HW, et al. Antiplatelet effects and pharmacodynamics of clopidogrel in cats. J Amer Vet Med Assoc 2004; 225:1406-1411.