Abstract
Objectives
The aim of the study was to describe the ultrasonographic characteristics of feline aortic thromboembolism (ATE) and determine potential associations between ultrasonographic findings and prognosis.
Methods
Data were retrospectively collected from the medical records (2013–2021) of cats that were diagnosed ultrasonographically with ATE based on the presence of a thromboembolus (TE) in the distal aorta beginning after the departure of the renal arteries.
Results
Twenty-nine cats were included in this study. The most frequent location for an ATE was at the aortic trifurcation. The median length of TEs was 9 mm (range 3.5–42.9). TEs appeared homogeneous and isoechoic to surrounding tissues in all cases. No correlation was found between the appearance of the TE and the duration of clinical signs. The obstruction of blood flow in the distal aorta at the aortic trifurcation was complete in 66% of cases and incomplete in 34% of cases. The survival rate was significantly lower when the obstruction was complete (11%, 95% confidence interval [CI] 2–34) compared with incomplete (70%, 95% CI 35–92). The arterial wall characteristics were as follows: smooth and thin (62%), and hyperechoic (38%).
Conclusions and relevance
Increased vascular obstruction of TEs was associated with a lower survival rate.
Introduction
Feline aortic thromboembolism (ATE) is a painful and life-threatening condition that represents approximately 0.3% of feline consultations. 1 Thrombosis is the pathological formation of a blood clot within a blood vessel, while a thromboembolus (TE) is defined as a dislodged blood clot that travels downstream within a blood vessel and subsequently creates a risk of blood flow obstruction. 2 Feline ATEs most frequently settle at the aortic trifurcation but can lodge in several other arteries, such as the brachial, cerebral or other abdominal arteries.2–5 Typically, feline ATE has a poor outcome, with euthanasia as high as 90% in some reports and a median survival time of 3 months.1,5,6 Although hypertrophic cardiomyopathy is considered the main cause of ATE in cats, other forms of cardiomyopathy have been associated with ATE. 5 Neoplasia and hyperthyroidism are also reported as other causes. 5
In cats, the clinical manifestation of ATE is characterised by acute paralysis or paresis, absent or weak arterial pulses, firm and painful limb musculature, and cold extremities.3,7,8 A final diagnosis of ATE in cats is usually based on physical examination, and can be confirmed by infrared thermography or direct visualisation of the TE with ultrasound (US), CT or MRI angiography.9–12 US has the advantage of being non-ionising, fast and non-invasive, but interpretation is highly operator-dependent.10,12 Despite the potential utility of this method, published reports on the ultrasonographic characteristics of ATE are currently lacking.
The objectives of this study were to describe the ultrasonographic features of feline ATE and to determine their correlation with prognosis. We hypothesised that feline ATEs are most frequently lodged in the aortic trifurcation and that the degree of blood flow obstruction may be correlated with survival rate.
Materials and methods
Inclusion criteria
This study included cats that were presented to the intensive care unit of a tertiary referral veterinary hospital (SIAMU, VetAgro Sup) for acute uni- or bilateral hindlimb paralysis or paresis between January 2013 and December 2021. Cats were included in the study if a diagnosis of ATE was made based on clinical findings, and a TE was visualised on US.
Medical records review
Medical information was obtained retrospectively from the database of the Veterinary School of Lyon by the first author (OE). The information collected for each case included signalment (age, sex, breed), abdominal US results, physical examination findings, echocardiography results, treatments received during hospitalisation, US and clinical follow-up (from database and telephone calls), outcome and autopsy results.
US data
A 4–10 MHz microconvex probe (ProSound Alpha 10; Aloka) and/or a 5–13 MHz linear probe (ProSound Alpha 10; Aloka) were used between January 2009 and September 2015 for 10 cases. An 8–11 MHz microconvex probe (Aplio 500; Toshiba) and/or a 12–18 MHz linear matrix transducer (Aplio 500; Toshiba) were used between October 2015 and December 2021 for the remaining 19 cases. All examinations were performed with the patient in dorsal or lateral recumbency.
US of the TE was performed either by a board-certified veterinary radiologist or a non-board-certified specialist in radiology. All US findings were stored in the medical records of the cats. All static images were saved and archived in Digital Imaging and Communications in Medicine (DICOM) files and were reviewed in agreement between two authors (OE and ES-W) using an image analysis workstation (iMac; Apple) and commercial software (Osirix; Pixmeo). The first author, a third-year radiology resident in training, was supervised by a board-certified veterinary radiologist for the assessment of this information. Both authors agreed with each other for all cases.
Vessels were scanned in both sagittal and transverse planes. A TE was defined as an echogenic intraluminal structure within an arterial vessel. The location of the TE was evaluated in the distal part of the aorta, beginning after the departure of the renal arteries. The echogenicity of the TE was described as hypoechoic, isoechoic or hyperechoic to surrounding tissues. The TE was characterised as either homogeneous or heterogeneous based on the detection of hypoechoic-to-anechoic areas within it. Blood flow was evaluated with colour Doppler US. Each TE was classified as obstructive or subobstructive on a scale of 1–4 based on the maximum degree of obstruction of the aortic trifurcation. A grade of 1 was given if the height or width of the TE was <50% of the height or width of the vessel in longitudinal or transverse section; a grade of 2 for 50 to <75%; grade 3 for 75 to <100%; and grade 4 for 100%. This grading is presented in Table 1. The degree of obstruction of the TE in the branches of the distal aorta was not scored given the small size of these vessels but was evaluated as complete or incomplete if blood flow was visualised distal to the TE on colour Doppler US. Arterial wall assessment was subjectively evaluated as smooth and thin or thickened and/or hyperechoic.
Grading of obstruction
Statistical analysis
Statistical analyses were performed by one author (TL). The data were gathered in a spreadsheet (Microsoft Excel 2013) and statistical analysis was performed using R 4.1.2 software (R Foundation for Statistical Computing). All descriptive data were expressed as percentages, and 95% confidence intervals (CIs) were calculated using the exact binomial formula with the function binom.test in R. When appropriate, comparisons between observed frequencies were performed with a χ2 test (chisq.test function in R). Continuous data are presented with their median, interquartile range (IQR; defined as the difference between the 75th and 25th percentiles) and range (minimum and maximum observed). Survivors were defined as alive cats at hospital discharge and non-survivors included naturally deceased cats and euthanased cats. The Mann–Whitney–Wilcoxon (MWW) test was used to compare the distribution of continuous variables between survivors and non-survivors (wilcox.test function in R). A P value <0.05 was considered to be statistically significant.
Results
Characteristics of the study population and clinical findings
Twenty-nine cats were included in this study. The median age of the cats was 6.4 years (IQR 7; range 1–18). Twenty-three cats (79%) were males (20 neutered [69%] and three intact [10%]) and six were neutered females (21%). Twenty cats were domestic shorthairs (69%). Other breeds were Chartreux (n = 2 [7%]), Bengal (n = 2 [7%]), Ragdoll, Sphynx, Birman, Maine Coon and Pixiebob (n = 1 each [3%]). For 10 cats (34%), the exact time of onset of clinical signs was known, and all these animals had their US within 6 h of the onset of clinical signs. The findings of all physical examinations and underlying diseases leading to feline ATE are summarised in Table 2.
Summary of clinical findings and outcomes in 29 cats with aortic thromboembolism
Data are presented as n (%) unless otherwise stated
CI = confidence interval
US findings
Locations of the TEs at the aortic trifurcation
Locations of feline ATEs are presented in Table 3. In 90% of cases (n = 26/29), feline ATE was located at the aortic trifurcation. The TE was most frequently detected in the aortic trifurcation, with no extension into one of the aortic branches in 12 cases (42%). The TE extended into both external iliac arteries in seven cases (24%), into the right external iliac artery in three cases (10%) and into the left external iliac artery in two cases (7%). In one cat (3%), the blood clot extended into both external iliac arteries and both internal iliac arteries, while in another cat (3%), the TE continued into the left internal iliac artery only.
Ultrasonographic findings of aortic thromboembolism (ATE) in 29 cats
Data are n (%) unless otherwise stated
Data presented for 26 cats
CI = confidence interval
Other TE locations
In three cats, an ATE was found in a location other than the aortic trifurcation (10%). The TE was visualised only in the left external iliac artery in two cases (7%), while in one cat (3%) the TE was detected in the left external iliac artery and continued into the left femoral artery. No TE was seen in the beginning of the sacral artery or in the right femoral artery in any cats.
US characteristics of the TEs
The major US findings of feline ATE are presented in Table 3. In the entire sample of cats, the median time between the onset of clinical signs and US examination was 24 h (IQR 20, range 2–192). The TEs appeared isoechoic to surrounding tissues in all cases (100%). The median TE length was 9 mm (range 3.5–42.9). The TEs appeared homogeneous in 24 cats (83%) and heterogeneous in five cats (17%; Figure 1). The arterial wall was smooth and thin in 18 cats (62%; Figure 2). Eleven cats (38%) showed increased vessel wall echogenicity (Figure 2), and in one of these cases, the vascular wall was subjectively noted as being thickened.
Example ultrasound images showing the appearance of a feline aortic thromboembolism. Longitudinal views of the thromboembolus (TE) were obtained with (a) a linear 18 MHz probe and (b) a linear 13 MHz probe. (a) Note the heterogeneous aspect of the TE, with some hypoechoic areas. (b) The TE appears homogeneous and isoechoic to surrounding tissues
Ultrasound images of the arterial wall facing the thromboembolus (TE). Longitudinal views of the TE were obtained with a linear 18 MHz probe. (a) Note the smooth and thin appearance of the arterial wall (arrow). (b) The arterial wall is slightly thickened and hyperechoic (arrow)
Grades of obstruction are presented in Figure 3. At the aortic trifurcation, the obstruction of blood flow by the TE was grade 4 in 17/26 cats (66%), grade 3 in 4/26 cats (15%) and grade 2 in 5/26 cats (20%). No cats showed grade 1 of vascular obstruction. Of the three cats (10%) that had TEs located elsewhere, vascular obstruction was complete in two cases and incomplete in one.
Ultrasound (US) images of different degrees of vascular obstruction, obtained with (a) a microconvex 8 MHz probe, (b,d–f) a linear 18 MHz probe and (c) a linear 13 MHz probe. (a,c,e) Longitudinal views; (b,d,f) transverse views. Note the grade 2 obstructions in (a) and (b); the degree of obstruction was 59% in (a) and 67% in (b). Note also the partial filling defect created by the thromboembolus (TE) on colour Doppler US. (c,d) Grade 3 obstruction in two different cats; the degree of obstruction was 86% in (c) and 80% in (d). (e,f) Grade 4 obstruction. The TE occupies 100% of the vascular diameter in these two images
Outcome and treatment
The outcomes for all cats are summarised in Table 2. The median time between the onset of clinical signs and euthanasia was 29 h (IQR 33.5, range 5–312), and the time between the onset of clinical signs and spontaneous death was 72 h (IQR 20, range 12–212). The median time between US and euthanasia was 24 h (IQR 12, range 2–120) and between US and spontaneous death was 48 h (IQR 24, range 6–120).
In 28 cats (96%), analgesia was administered upon presentation. Diuretic treatment was administered to 16 cats (55%). Twenty-seven cats (93%) received specific medical treatment for ATE; the range of drugs used in the treatment of ATE and the associated survival rates are summarised in Table 4.13,14 The only adverse effect reported for a few cats during these treatments was the presence of nausea when taking clopidogrel. In these cases, the treatment was changed to aspirin. In comparing the use of medical thrombolysis, antiplatelets alone or a combination of antiplatelets and anticoagulants, no significant difference was found in survival rates following any of the treatments.
Drugs used in the treatment of and associated survival rates in 29 cats with aortic thromboembolism
The administration of tissue plasminogen activator (t-PA) was always associated with anticoagulants (enoxaparin) and/or antiplatelets (clopidogrel, aspirin)
CI = confidence interval; IV = intravenous; PO = per os; SC = subcutaneous
Prognostic factors and US appearance of the TE
The median number of vessels into which the TE extended was two in non-survivors (range 1–5) and one in survivors (range 1–3). The maximum number of vessels into which the TE extended was five in a single non-surviving cat, namely the distal aorta at the aortic trifurcation and both external and internal iliac arteries. However, the number of vessels affected by the TE was not statistically significantly different between survivors and non-survivors (P = 0.26, MWW test). Furthermore, the survival rate was not significantly affected by the location of the TE (aortic trifurcation vs external iliac artery P = 0.45). The median length of the TEs was 8.9 mm (range 4.7–42.9) for non-survivors and 10.3 mm (range 3.5–25) for survivors, but this difference was not statistically significant (P = 0.5746).
For the TEs located at the aortic trifurcation, the proportion of survivors with each grade of obstruction is presented in Table 5. The survival rate was significantly lower with higher grades of obstruction (P = 0.0035).
Proportion of survivors with each grade of obstruction at the aortic trifurcation in 26 cats
Data are presented as n (%) unless otherwise stated
CI = confidence interval
Among all TE locations, 17/20 non-survivors (85%, 95% CI 62–97) had complete vascular obstruction. Seven of the nine survivors (78%, 95% CI 40–97) had partial vascular obstruction and the other two (22%, 95% CI 3–60) had complete obstruction. The survival rate was statistically significantly lower (P = 0.004) when obstruction was complete (11%, 95% CI 2–34) compared with incomplete (70%, 95% CI 35–92).
All 17 cases with a grade 5 obstruction (100%, 95% CI 80–100) presented bilateral paralysis and absent femoral pulses. In contrast, cats with a grade 3 or 4 obstruction presented with bilateral paralysis significantly less frequently (44%, 95% CI 14–79; P = 0.004) and bilateral paresis more frequently (56%, 95% CI 21–86; P = 0.004). Within this group, two cats (22%, 95% CI 3–60) had a weak femoral pulse and seven (78%, 95% CI 40–87) had an absent femoral pulse, but the proportions for weak femoral pulse were not statistically different between grades 3/4 and grade 5 (P = 0.21). All three cases in which the TE was settled in another location than the aortic trifurcation presented paresis (uni- or bilateral). The proportion of survivors was significantly higher (P = 0.006) in cats presenting uni- or bilateral paresis (75%, 95% CI 35–97) compared with cats with paralysis (14%, 95% CI 3–36), but there was no statistically significant difference between survivors and non-survivors in the presence or absence of a femoral pulse (P = 0.76).
US follow-up
US follow-up was available for three cats.
Cat 1
This first cat had a TE lodged at the aortic trifurcation that extended into the left external iliac artery, with grade 5 vascular obstruction. A first US follow-up was performed immediately after medical thrombolysis and revealed no changes. A few hours after the US, the cat had a weak pulse in the right hindlimb, then in the left hindlimb. Another US was performed 24 h later, revealing complete disappearance of the TE. The cat was determined to have made a complete physical recovery and was discharged.
Cat 2
The second cat had a TE settled in the left external iliac artery extending into the left femoral artery and had complete vascular obstruction. This cat had repeat US performed 24 h and 48 h after medical thrombolysis. After 24 h, no change was observed in the US, but some voluntary movements were observed, along with the gradual reappearance of a weak pulse in the left hindlimb. After 48 h, the TE had decreased in size and appeared hypoechoic and heterogeneous, in contrast to its previous appearance as isoechoic to surrounding tissues and homogeneous. At this time, clinical improvement continued and recoloration of the digits was visible. However, 2 days later, the cat was euthanased owing to non-responsive congestive heart failure and hyperkalaemia.
Cat 3
The TE in the third cat was lodged at the aortic trifurcation and extended into both external iliac arteries. The degree of vascular obstruction was of grade 5 at the aortic trifurcation and was complete into both external iliac arteries. This cat had a US follow-up 4 days after medical thrombolysis, which revealed a regression in the size of the TE from 7.7 mm to 2.5 mm. There was partial recovery of blood flow, with grade 4 vascular obstruction at the aortic trifurcation and incomplete vascular obstruction in both external iliac arteries. Unfortunately, hyperkalaemia and cardiac decompensation led to the death of the animal.
Discussion
To our knowledge, this study is the first to describe the ultrasonographic findings of feline ATE and to investigate associations between ultrasonographic findings and prognosis. Consistent with the existing literature, 12 the most frequent location for feline ATE was at the aortic trifurcation (26 cats [90%]). In most cases, there was no visible extension of the TE into one of the aortic branches. When the TE did extend into one of the aortic branches, the most frequent location was into both external iliac arteries. When TEs were found in one or both internal iliac arteries (two cats), they always extended from the aortic trifurcation. In our study, a TE was never detected at the beginning of the sacral or right femoral artery. The median length of the TEs was 9 mm, with no significant difference between survivors and non-survivors.
A previous study reported that the ultrasonographic appearance of thrombi depended on their duration. 11 Immature or acute thrombi have been described as hypoechoic to anechoic and homogeneous, and thus difficult to distinguish from flowing blood on B mode US.12,15 Within 6 h of the induction of experimentally induced thrombi, however, echogenicity of the forming thrombus rapidly increased. 16 Finally, Drost et al 15 reported that chronic thrombi typically appeared echogenic to hyperechoic and heterogeneous. In our study, the most frequent ultrasonographic appearance of feline ATE was isoechoic to surrounding tissues and homogeneous. In the current study, 10 cats had a US examination within 6 h of the onset of clinical signs, according to the medical records. However, we identified no correlation between the appearance of the TE and the time since the discovery of clinical signs by the owners. This is likely due to the difficulty of objectively determining when obstructive TE first occurs; it is thus possible that the observed onset of clinical signs by owners does not reflect the actual onset of obstruction. Furthermore, ATE occurs when a thrombus, typically formed in a dilated left atrium or auricle, embolises to a peripheral artery. 6 The thrombus has already been present for quite a long time when it breaks off to form a TE. This likely explains why all the TEs in our study were isoechogenic to surrounding tissues and homogeneous. In a recent study of the use of thrombolysis in feline ATE, there were similar rates of survival and complications in cats that were treated with t-PA and those that received the current standard of care. 14
In our sample population of cats, the degree of obstruction of blood flow at the aortic trifurcation was of grade 4 in 65% of cases and grades 2 or 3 in 35% of cases. None of the cats had a grade 1 of obstruction. The authors hypothesised that if there were thrombi of such size, they would have lodged further into smaller vessels (eg, distal collaterals in the hindlimbs) and would not have been seen them on US. To our knowledge, these represent the first published data on the degree of obstruction in feline ATE. In more than 90% of cases, the obstruction was complete when the TE extended from the aortic trifurcation into one of its branches. There was a significantly higher frequency of complete obstruction in non-survivors than in survivors. Thus, the degree of obstruction is the main negative prognostic factor identified in this study.
We included euthanased cats in the non-survivors, which led to an overall survival rate of 31% (n = 9/29) in our study. This survival rate is comparable with that in other studies.5,6,17,18
No statistically significant difference was found in a univariate comparison of the survival rates for the treatments applied here. However, our study was not designed to assess the efficacy of these treatments and we did not account for any potential confounding factors in the univariate analysis. Further studies are needed to assess the relative efficacy of these treatments. Based on our findings, it appears that the degree of vascular obstruction may have a stronger influence on survival than the treatments administered. Unsurprisingly, the degree of vascular obstruction corresponded to the clinical signs presented by the animal. In all cases of grade 4 obstruction, there was bilateral paralysis with absent femoral pulses. Bilateral paralysis was also present in fewer than half of cats with grade 2 or 3 obstruction. It is possible in these cases that other TEs were lodged further in the branches of the distal aorta and were not visualised on US. Paresis was also present when the TE was only located in the branches of the distal aorta.
In our study, 23 cats (79%) with ATE were males, of which 20 were neutered. This aligns with previous reports of an increased incidence in male cats due to their predisposition to cardiomyopathies. 5,6,17–19
Our study has several limitations, the first being the small sample size, which limits our ability to draw conclusions from the data. Secondly, the lack of accurate knowledge regarding the time between the onset of clinical signs and the US examination made it difficult for us to characterise the relationship between the time since the thromboembolic event and the ultrasonographic appearance of the TE, in particular its echogenicity. Finally, the lack of US follow-up over time is another limitation. In general, follow-up examinations can be challenging in cats with ATE due to the low short- and medium-term survival rates.
Conclusions
The results of the current study support the use of abdominal US as a useful and safe diagnostic tool for the evaluation of feline ATE. In our sample, the most common ultrasonographic characteristics of TEs were an isoechoic to surrounding tissues and homogeneous intraluminal structure, with a median length of 9 mm. Feline ATE was most frequently located at the aortic trifurcation in 90% of cases, and increased vascular obstruction was associated with non-survival. Further studies with increased US follow-up are needed to better evaluate the ultrasonographic evolution of ATE over time.
Footnotes
Acknowledgements
The authors would like to thank Dr Camille Lecourtois for her help with the recruitment of cases, and Dr Mark Kim for help with manuscript editing.
Conflict of interest
The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
Funding
The authors received no financial support for the research, authorship, and/or publication of this article.
Ethical approval
The work described in this manuscript involved the use of non-experimental (owned or unowned) animals. Established internationally recognised high standards (‘best practice’) of veterinary clinical care for the individual patient were always followed and/or this work involved the use of cadavers. Ethical approval from a committee was therefore not specifically required for publication in JFMS. Although not required, where ethical approval was still obtained, it is stated in the manuscript.
Informed consent
Informed consent (verbal or written) was obtained from the owner or legal custodian of all animal(s) described in this work (experimental or non-experimental animals, including cadavers) for all procedure(s) undertaken (prospective or retrospective studies). No animals or people are identifiable within this publication, and therefore additional informed consent for publication was not required.
