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Effects of steroids on the heart in dogs | VETgirl Veterinary Continuing Education Podcasts

In today’s VETgirl online veterinary podcast, we review the use of steroids and whether or not steroids truly have detrimental effects on the heart. We’ve been taught since our early years in veterinary school to have a healthy respect for glucocorticoid use. Understandably, there are many unwanted side effects to steroids such as weight gain, immune system suppression, and polyuria, to name the most commonly encountered. But there are also many medical uses for steroids such as intentional immune suppression and to combat inflammatory processes. In cats, we have produced evidence that long-acting glucocorticoid use can precipitate development of congestive heart failure (CHF). To date, we do not have published supportive evidence for this in dogs. So, Masters et al out of Iowa State University wanted to evaluate this in a prospective study called “Effects of short-term anti-inflammatory glucocorticoid treatment on clinicopathologic, echocardiographic, and hemodynamic variables in systemically healthy dogs.” to see what cardiovascular effects anti-inflammatory doses of glucocorticoids would have on canine patients with no preexisting structural heart disease.

Ten client-owned dogs diagnosed with allergic dermatitis were used as the treatment group to receive anti-inflammatory doses of prednisone. These dogs were screened and found to have no evidence of concurrent systemic disease, no concerns on baseline blood work screening, and had not received any hemodynamically active medications prior to this study. The control group consisted of 10 healthy dogs that were roughly matched in age, sex, neuter status, and body weight to the treatment dogs. The treatment group dogs were administered a tapering course of oral prednisone starting with a 1 mg/kg dose once daily for 14 days, followed by a 0.5 mg/kg dose once daily for 3 days, then 0.5 mg/kg once every 48 hours for 3 doses, and then discontinued. Dogs were allowed to eat their commercial diets, but caution was taken to ensure they ate between 6-8AM on days they would enter the hospital for evaluation; they were evaluated on days 0, 7, 14, and 35 of the study. The following diagnostics were evaluated on each dog in the study: systolic blood pressure, body weight, baseline blood work (CBC and Chemistry), urinalysis, transthoracic echocardiogram (performed by one board-certified cardiologist), and a plasma volume calculation was performed. On days 0 and 14, all dogs had an insulin-to-glucose ratio and serum fructosamine concentration performed. Blood glucose was measured on days 1 through 4 in the treatment group. Prednisone concentration was measured in the treatment group on days 0, 14, and 35.

As we would expect, the treatment group exhibited a higher neutrophil count at day 7 and 14, elevated monocytes at all time points, and decreased eosinophils that returned to baseline at day 35. Interestingly, we tend to think platelet count will increase from steroid use as is seen in conditions of excessive glucocorticoid production (such as with hyperadrenocorticism), but no significant platelet increase was observed in this study. Three serum biochemical variables significantly changed from reference range including an increase in serum ALP and ALT activity, and a decrease in serum chloride concentration. Albumin and total protein concentrations increased, possibly as a result of increased production and lifespan of albumin. Urine specific gravity and urine pH both decreased in the treatment group owing to prednisone’s diuretic effect and hydrogen ion-secreting effect in the kidneys. Surprisingly, the cholesterol levels in treated dogs declined (still within reference intervals), which is opposite of what we would have expected from prednisone therapy. Treatment dogs also exhibited a drop in body weight, likely attributed to dehydration from steroid-induced polyuria and/or decreased muscle mass.

No changes in blood sugar or insulin-to-glucose ratios were detected in either group, and even within the first 4 days of starting prednisone, no significant elevation in blood glucose was detected. For unknown reasons, the control group reached a higher fructosamine concentration at day 14 than the treatment group, but both groups remained within the fructosamine concentration normal reference range throughout the study. No significant change in plasma volume was detected at any point during the study. These findings suggest that anti-inflammatory doses of prednisone do not cause diabetogenic effects in “normal” dogs, which is in contrast to what has been shown in cats. The theory in cats is that the glucocorticoids causes a transient hyperglycemia with resultant increase in plasma volume that can precipitate CHF, but this present study disproved this theory in “normal” dogs.

Sodium concentrations in the treatment dogs did not increase and plasma volume, as described above, also did not increase. Lack of these two factors essentially eliminates the theory of prednisone causing sodium retention and resultant plasma volume increase. Therefore, the mineralocorticoid properties of prednisone do not appear to be a precipitating factor in development of CHF when used at anti-inflammatory doses in dogs.

This study also looked at cardiac structures and indices of cardiac function after starting prednisone therapy. Only 3 of the cardiac indices were significantly different between the treatment and control groups [e.g., the left ventricular internal diameter at end diastole (LVIDd), the early diastolic mitral inflow velocity to early diastolic mitral annular motion (E:Ea ratio), and the global longitudinal strain (GLS)]. The LVIDd and E:Ea ratio both increased mildly, and the GLS decreased mildly. The changes were not outside reference ranges, and so, were considered clinically insignificant. Therefore, the authors conclude that anti-inflammatory doses of prednisone do not cause cardiac remodeling or other structural changes to precipitate CHF in normal dogs.

At day 7, the treatment group exhibited an elevation in systolic blood pressure compared to baseline. The change in systolic arterial blood pressure was considered clinically significant. The mean systolic arterial blood pressure in the treatment group increased from 148 mmHg to 167 mmHg, which falls into the category of systemic hypertension. To further complement this finding, the authors found that heart rates in the treatment group decreased during treatment with prednisone, attributable to a baroreceptor response from the increase in blood pressure. However, the decrease in heart rate failed to reach statistical significance. The finding of increased systolic arterial blood pressure does provide a plausible theory by which dogs with preexisting heart disease could develop CHF owing to an increase in afterload. The authors provide possible explanations for how prednisone therapy can cause an increased afterload. The mineralocorticoid effects can cause sodium retention and resultant increase in plasma volume. (However, the findings of this study suggested that anti-inflammatory doses of prednisone did not cause plasma volume increases or a change in sodium concentration in dogs). Other possible mechanisms include activation of the renin-angiotensin-aldosterone system, increasing vascular sensitivity and receptivity to endogenous catecholamines, suppression of the body’s vasodilatory systems or enhancement of the vasoconstrictive systems, and precipitation of glomerulosclerosis. Further studies are needed to determine why prednisone appears to cause systemic hypertension in dogs.

So, what do we take away from this VETgirl podcast? Based on this study, there’s no evidence that anti-inflammatory doses of prednisone will precipitate CHF in “normal” dogs. The authors offer that if these doses precipitate CHF in dogs with preexisting heart disease, a possible theory may be prednisone’s indirect vasomotor effects causing an increase in SAP and increased afterload. The authors recognize the main limitation of this study, which is small sample size, and also note that blood samples in the treatment groups were not obtained at times of peak prednisone concentrations in the blood, which could cause dampened test results. However, in VETgirl’s opinion? This study rocked! It was prospective and really helped provide strong evidence based on the clinicopathologic, echocardiographic, and hemodynamic variables that were assessed in this study. Further studies are needed to determine if long-term anti-inflammatory prednisone use or use of these doses in dogs with evidence of heart disease will cause any significant changes to precipitate CHF in dogs. Keep in mind that this study evaluated “normal” dogs – those without cardiac disease – so we still want to be cautious using steroids in dogs with underlying heart disease!

References:
1. Masters AK, Berger DJ, Ware WA, et al. Effects of short-term anti-inflammatory glucocorticoid treatment on clinicopathologic, echocardiographic, and hemodynamic variables in systemically healthy dogs. AJVR 2018;79(4):411-423.

Abbreviations:
ALP = Alkaline phosphatase
ALT = Alanine aminotransferase
CHF= congestive heart failure
E:Ea ratio = Early diastolic mitral inflow velocity to early diastolic mitral annular motion
GLS = Global longitudinal strain
LVIDd = Left ventricular internal diameter at end diastole
SAP = systolic arterial blood pressure
USG = Urine specific gravity

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