Recent increases in the prevalence and severity of wildfires in some regions have resulted in an increased frequency of veterinary burn patients. Few studies exist regarding diagnostics and management of burn wounds in veterinary patients and current knowledge is extrapolated from human literature and research models. Post-burn cardiac injury is a common finding and predictor of mortality in human patients and echocardiography is an important tool in monitoring response to therapy and predicting outcome. We describe the notable findings from cats naturally exposed to California wildfires in 2017 and 2018. Domestic cats (n = 51) sustaining burn injuries from the Tubbs (2017) and Camp (2018) wildfires were prospectively enrolled and serial echocardiograms and cardiac troponin I evaluations were performed. Echocardiograms of affected cats revealed a high prevalence of myocardial thickening (18/51) and spontaneous echocardiographic contrast and thrombi formation (16/51). Forty-two cats survived to discharge and 6 died or were euthanized due to a possible cardiac cause. For the first time, we describe cardiovascular and coagulation effects of thermal burn and smoke inhalation in cats. Further studies in veterinary burn victims are warranted and serve as a translational research opportunity for uncovering novel disease mechanisms and therapies.

Introduction

A surge in Food and Drug Administration (FDA) consumer complaints identified concerns that legume-rich, grain-free diets were associated with nutritionally-mediated dilated cardiomyopathy (DCM). Golden retrievers represent the most reported breed affected by this condition and previous studies documented the disease is responsive to dietary change and taurine supplementation. Although dietary findings across cases are compelling, prospective studies with control groups are lacking. The role of diet in developing taurine deficiency and echocardiographic changes consistent with DCM in healthy dogs is unknown.

Objectives

We hypothesized that golden retrievers eating non-traditional diets are at a higher risk of having taurine deficiency and nutritionally-mediated DCM compared with those eating traditional commercial diets. We aimed to compare taurine concentrations and echocardiographic indices of systolic function between golden retrievers in each diet group and elucidate associations between diet and these variables. Additionally, we aimed to generate breed-specific reference intervals for whole blood and plasma taurine concentrations.

Animals

86 golden retrievers.

Methods

Golden retrievers eating traditional or non-traditional diets were evaluated and diet history, taurine concentrations and echocardiographic data were collected. Dietary features, taurine concentrations and echocardiographic findings were compared between diet groups. Relative risks were calculated for the likelihood of echocardiographic abnormalities and taurine deficiency in each diet group. Breed-specific reference intervals were constructed for taurine concentrations in dogs from the traditional diet group.

Results

Golden retrievers eating non-traditional diets had significantly lower taurine concentrations and more frequent systolic dysfunction. Breed specific reference intervals are higher than previously reported across breeds.

Conclusions

Non-traditional diets, which were typically grain-free and contained legumes in this study, were significantly associated with and have increased relative risk for the identification of taurine deficiency and echocardiographic abnormalities consistent with nutritionally-mediated DCM. These findings were identifiable in the absence of clinical signs and support the findings of multiple previous studies and the ongoing FDA investigation.

Hypertrophic cardiomyopathy (HCM) is the most prevalent cardiac disease in cats and lacks efficacious preclinical pharmacologic intervention, prompting investigation of novel therapies. Genetic mutations encoding sarcomeric proteins are implicated in the development of HCM and small molecule myosin inhibitors are an emerging class of therapeutics designed to target the interaction of actin and myosin to alleviate the detrimental effects of inappropriate contractile protein interactions. The purpose of this study was to characterize the pharmacodynamic effects of a single oral dose of the novel cardiac myosin inhibitor aficamten (CK-274) on cardiac function in purpose bred cats with naturally occurring A31P MYBPC3 mutation and a clinical diagnosis of HCM with left ventricular outflow tract obstruction (LVOTO). Five purpose bred cats were treated with aficamten (2 mg/kg) or vehicle and echocardiographic evaluations were performed at 0, 6, 24, and 48 h post-dosing. High dose aficamten (2 mg/kg) reduced left ventricular fractional shortening (LVFS%) by increasing the LV systolic internal dimension (LVIDs) and reduced isovolumic relaxation time (IVRT) compared with baseline without significant adverse effects. The marked reduction in systolic function and reduced IVRT coupled with an increased heart rate in treated cats, suggest a lower dose may be optimal. Further studies to determine optimal dosing of aficamten are indicated.

Hypertrophic cardiomyopathy (HCM) is the most prevalent inherited cardiac disease in humans and cats and lacks efficacious pharmacologic interventions in the preclinical phase of disease. LV outflow tract obstruction (LVOTO) is commonly observed in HCM-affected patients and is a primary driver of heart failure symptoms and reduced quality of life. Novel small-molecule cardiac myosin inhibitors target actin-myosin interactions to alleviate overactive protein interactions. A prospective, randomized, controlled cross-over study was performed to evaluate pharmacodynamic effects of two doses (0.3 and 1 mg/kg) of a next-in-class cardiac myosin inhibitor, aficamten (CK-3773274, CK-274), on cardiac function in cats with the A31P MYBPC3 mutation and oHCM. Dose-dependent reductions in LV systolic function, LVOT pressure gradient, and isovolumetric relaxation times compared to baseline were observed. Promising beneficial effects of reduced systolic function warrant further studies of this next-in-class therapeutic to evaluate the benefit of long-term administration in this patient population.