Submitted by: Patricia Shea, DVM
Prognostic value of neutrophil-to-lymphocyte ratio in cats with hypertrophic cardiomyopathy.
Fries RC, Kadotani S, et al.
Hypertrophic cardiomyopathy (HCM) is cats’ most common acquired cardiac disease and can be present and significant even in apparently healthy cats. HCM is estimated to exist in 16-34% of the healthy domestic feline population. This condition can progress to congestive heart failure (CHF) in some animals. The “gold standard” for HCM diagnosis is echocardiography, which also facilitates establishing a prognosis for an individual patient and provides risk assessment for the eventual development of CHF. However, echocardiography is not universally accessible and affordable for the owners of cats with HCM, and even with this modality, additional prognostic indicators for feline cardiomyopathies are likely to be useful.
As in humans, cardiac function biomarkers are now available for veterinary species, including cats. The most well-known are N-terminal brain natriuretic peptide (NT-proBNP), cardiac troponin I (cTnI), and cardiac troponin T. These assays can identify patients who need further cardiac workup; cTnI, if significantly elevated, has been shown to be a negative prognostic indicator for cats with HCM.
In this prospective observational study of 96 client-owned cats, the authors hypothesized that the neutrophil-lymphocyte ratio (NLR), which is readily accessible on any complete blood count (CBC) and is a hematological biomarker of inflammation and stress, could serve as a prognostic indicator in cats with HCM, as it does in veterinary patients, including cats, with neoplastic and systemic inflammatory diseases. The NLR is simply the number of neutrophils divided by the number of lymphocytes listed on the CBC. In humans with a variety of cardiac and arterial diseases, including heart failure and HCM, a higher NLR has been shown in a number of studies to be associated with a poorer prognosis for the patient. However, it is important to note that in both animals and humans, neutrophil counts can increase and lymphocyte numbers decrease due just to the effects of physiologic stress, so the NLR is not necessarily always a biomarker of inflammatory or neoplastic disease.
The study population comprised 38 healthy cats and 58 cats with HCM, enrolled in the study between April 2016 and May 2021. The entire study group was middle-aged. The median age of the healthy cats was 6.2 ± 1.2 years; cats with HCM only had a median age of 6.7 ± 0.75 years, and the median age of patients with both HCM and CHF was 7.5 ± 2.0 years. The healthy group comprised 24 males and 14 females; the HCM-only group contained 16 males and 13 females, and the HCM/CHF group included 18 males and 11 females.
All animals were evaluated with a physical examination, indirect blood pressure measurement by Doppler, CBC, biochemical screen including a total thyroxine (T4) assay, urinalysis, transthoracic echocardiogram, and thoracic radiography. HCM diagnosis was defined by a diastolic left ventricular free wall or interventricular septal thickness > 6 mm on echocardiography. Cats with systemic hypertension, pulmonary hypertension (as estimated by Doppler echocardiography), non-HCM cardiac disease, hyperthyroidism, use of glucocorticoids in the three months prior to the evaluation, and any other serious systemic disease with significant potential to limit survival, were eliminated from the study. Outcomes were assessed by follow-up examinations and telephone interviews with owners.
Healthy cats were defined as those for whom all diagnostic tests were within normal limits. Heart failure was identified in cats in the HCM group based on thoracic radiographic findings. The HCM group was subdivided into stage B (healthy, with subclinical heart disease; n=29) and stage C (heart failure; n=29) based on the American College of Veterinary Internal Medicine guidelines for classification, diagnosis, and management of cardiomyopathy in cats. The healthy cats and the stage B cats received no other medications besides topical flea and heartworm preventatives. All patients diagnosed with heart failure (stage C) were required to be receiving oral furosemide upon hospital discharge.
Median NLR for the healthy group was 1.80 (range, 0.41-8.85); for the stage B group, the median NLR was 2.48 (range, 0.73-7.35); for stage C, those with CHF, the median NLR was 5.11 (range, 1.55-48.1). In this latter group, the maximum left atrial diameter on echocardiography (LAmax), and NLR were the significant variables predicting survival time in the univariable model. In the multivariable analysis, NLR alone was significant in this regard, implying that NLR, at least in this population of cats with CHF, is an independent predictor of cardiac death.
For each patient, the endpoint of the study was sudden cardiac death or euthanasia for CHF. Survival time was measured as the time from enrollment in the study to this endpoint. None of the cats were lost to follow-up. Almost half of the cats (43/96; 44.8%) had died by the end of the study period. One healthy cat was euthanized due to septic peritonitis, and four stage B cats were euthanized due to non-cardiac diseases. All of the stage C cats who died were euthanized or died of causes attributable to complications of CHF: refractory pulmonary edema or pleural effusion, arterial thromboembolism, and sudden death.
The Median follow-up time for the entire group was 344 days. Survival time was analyzed for the HCM and HCM/CHF cats only, and for the entire cohort, the median survival time (MST) was 265 days. The stage B (HCM only) cats had significantly longer MST (456 days; range, 67-1043 days) than those in stage C (HCM and CHF), where the MST was 188 days (range, 19-546 days).
Although the elevated NLR in the HCM groups could in part be due to physiologic stress, systemic and myocardial inflammation is known to exist in feline HCM. Cats with CHF due to cardiomyopathies, including HCM, have been found to have increased plasma concentrations of tumor necrosis factor alpha (TNF-A), which may promote peripheral lymphocyte apoptosis, as well as increased serum amyloid A. Recent research has also demonstrated that systemic inflammatory diseases activate the transcription of inflammatory cytokines and remodeling enzymes in the feline myocardium, but it is still unclear if this process ultimately results in cardiac myocyte injury and death. Connections between inflammation and HCM in humans have also been documented.
The potential association between local and systemic inflammation and arterial thromboembolism (ATE), a complication of HCM in some cats, is another fascinating avenue of inquiry. Given that development of ATE is not universal in cats with left atrial enlargement, there may be other factors contributing to this comorbidity, including hypercoagulability. In a 2015 study of cats with a non-cardiac disease, pro-inflammatory, and remodeling markers were found in higher levels in the myocardium of feline atria than in the ventricles. Data reported in the present paper demonstrate that increased NLR is significantly associated with the presence of spontaneous echo contrast (“smoke”) and thrombus within the left atrium, also suggesting a link between ATE and inflammation.
Limitations of this study include its observational nature and that NLR as well as other variables were not monitored over time. In addition, there was no antemortem assessment of myocardial inflammation with magnetic resonance imaging, and only mortality due to cardiac disease was analyzed.
Sterile neutrophilic dermatitis in a cat associated with a topical plant-derived flea preventative.
Zhou Z, Noland E, et al.
Most pet owners visit pet stores and other brick-and-mortar- or online retailers for pet foods and supplies, likely more often than they obtain these commodities from veterinary clinics or their online stores. Moreover, many pet owners, following human trends, seek “natural” or “holistic” products for their animals, even though such terms have no legal definition. The following case report, involving a 4-year-old female spayed domestic shorthair cat, is a cautionary tale.
Cats and dogs can experience significant adverse effects when exposed to plant-derived flea preventatives, even when these products are applied in accordance with label directions. In cats, agitation and hypersalivation are common side effects observed with the use of these products, but cutaneous reactions similar to those described in this case study have not been previously reported.
Sterile neutrophilic dermatitis (SND) is rarely reported in both humans and animals. In humans, three forms of SND have been described: Sweet’s syndrome, pyoderma gangrenosum, and superficial amicrobial pustulosis. Several cases of similar disease, not associated with the application of an over-the-counter flea product, have been reported in dogs. In cats, only one previously published case report exists, in which no microbial culture was performed.
The patient presented with acute fever (104°F), lethargy, and skin lesions. Eight days prior to presentation, the owner applied an over-the-counter topical flea preventative containing oils of peppermint, clove, and lemongrass, as well as canola oil, vanillin, and citric acid. The clinical signs appeared six days after application of the product and included multifocal ulcerations and crusts on the lips and pinnae, and a large number of pustules, some of which coalesced into larger bullous plaque-like lesions. These plaque-like lesions, which were present on the ventral abdomen and extended into the thorax and medial thighs, had ulcerated and appeared painful. Paronychia was identified on all four paws.
Laboratory evaluation demonstrated a mild left shift and bilirubinemia; thoracic radiographs and abdominal ultrasound findings were unremarkable. No ectoparasites were found on deep skin scrapings. An aerobic bacterial culture from one of the pustules did not grow. Cytologic samples from the pinna, nailbed, and lesions on the cat’s ventral aspect all demonstrated a similar neutrophilic inflammation without any bacteria or acantholytic cells. The cat was sedated and three punch biopsies were taken from the skin of the ventral abdomen.
Neutrophilic dermatitis ranging from mild interstitial and dense perifollicular neutrophilic infiltrates to large abscess-like accumulations of neutrophils and small neutrophilic pustules were found in the biopsies. Moderate to severe edema was also observed in the biopsies. As in the cytologic findings, no infectious agents or acantholytic cells were identified on histopathology. The application of a Luna stain demonstrated that the granulocytes in the biopsies were definitely not eosinophils. Caliciviral infection was ruled out with immunohistochemistry.
The presence of an immune-mediated disease was assumed while the patient was awaiting the results of the histopathology, and treatment with intravenous dexamethasone (0.28 mg/kg once daily) was initiated. Improvement in the lesions and resolution of the fever was noted by the next morning and the cat was more active and appeared less painful. Prednisolone, 0.94 mg/kg PO twice daily, was sent home with the cat at hospital discharge. Eleven days later, most of the skin lesions had resolved, and by 54 days after discharge, the skin lesions were no longer present. The prednisolone was tapered and discontinued, and at follow-up (237 days later), there were no new lesions.
Although the skin at the application site of the topical product (dorsal neck) was unaffected, the authors suspect that the trigger for the severe SND in this patient was the topical plant-derived oil flea preventative, given that the clinical signs appeared 6 days after application of this product. Pemphigus foliaceus, the only common sterile neutrophilic dermatosis in cats, was a major differential diagnosis for this cat’s presentation. However, this disease, which can manifest as a drug reaction, was ruled out due to the lack of acantholytic cells found on cytologic and histopathologic evaluations. There was also no recurrence of the clinical signs after prednisolone was discontinued, further eliminating pemphigus foliaceus as a possibility. The large abscess-like pools of neutrophils observed in this feline patient are similar to those found in dogs with pyoderma gangrenosum, and the fever and neutrophilic infiltrate in the superficial and mid-dermis bear similarities to the human Sweet’s syndrome.