Borgeat K, Niessen SJM, et al. (2018) Time spent with cats is never wasted: Lessons learned from feline acromegalic cardiomyopathy, a naturally occurring animal model of the human disease. PLoS ONE 13(3): e0194342
A number of cardiac diseases identified in cats, including hypertrophic cardiomyopathy, arrhythmogenic right ventricular cardiomyopathy, and restrictive cardiomyopathy, have clinical and pathologic characteristics very similar to these conditions in humans. Therefore, several feline cardiomyopathies are considered useful animal models of human cardiomyopathies.
Acromegaly is the name given to the disease of skeletally mature humans and animals that suffer from either a functional pituitary gland adenoma or hyperplasia of the pars distalis of the anterior pituitary gland. These pituitary abnormalities are associated with hypersomatotropism (HS), involving excessive production of growth hormone and insulin-like growth factor-1 (IGF-1), which promote acromegaly as well as other abnormalities in adult individuals. Approximately 60% of humans with HS will die from cardiovascular disease. Even in those human HS patients who do not experience cardiac failure, there is increased left ventricular (LV) mass, increased LV wall thickness as measured by echocardiography, impaired cardiac function, and a high prevalence of cardiac valvular disease. Histopathologic evaluation of hearts thus diseased demonstrates myocyte hypertrophy, myocardial fibrosis, and sometimes cellular infiltrates or small vessel disease.
HS is well documented in cats and appears to be increasing in prevalence in cats as well as humans, possibly due to exposure of both species to environmental toxins such as organohalogenated compounds. As in humans, HS tends to develop in cats during middle to old age. One-quarter to one-third of cats with diabetes mellitus (DM) also have HS; however, there are a few reports of acromegalic cats who do not have DM. A substantial number of middle-aged to older cats have cardiomyopathies, especially hypertrophic cardiomyopathy (HCM), and it is possible that some cats with HS have incidental/unrelated primary HCM.
The present study, which did not utilize experimental animals, was designed to characterize a specific HS-associated cardiomyopathy in cats, while controlling for primary HCM and diabetic cardiomyopathy, which could be confounding factors in some cases. A control group of 16 healthy geriatric cats without any known cardiac, endocrine, or other systemic disease was recruited through two veterinary general practices. Also included were a group of 67 cats with confirmed HS, all of whom were also diabetic, and 24 diabetic cats (DM group), also with no other known endocrine diseases or cardiac disease, who were patients at a veterinary teaching hospital. All of the cats were evaluated with Doppler blood pressure measurements, echocardiography, and clinicopathologic blood testing, including assays for IGF-1, which is a biomarker for HS, fructosamine, total T4, NTproBNP, and cardiac troponin 1. All cats of both sexes included in this portion of the study had been gonadectomized years before their enrollment in the study.
In addition, records of the anatomic pathology service of the veterinary teaching hospital were searched for histopathological information on three age-matched groups of 21 patients each: (1) cats with confirmed HCM who had clinical signs of congestive heart failure or a history suggestive of sudden cardiac death; (2) cats with confirmed HS, regardless of history of clinical signs of cardiac disease; and (3) a control group of geriatric cats with no history of cardiac disease and no history or necropsy findings associated with either DM or HS. Occult HCM was possible in the control group cats, and this was deliberately not excluded given that some of the HS group cats could also have had concurrent primary HCM as well as secondary cardiac disease associated with the HS.
Echocardiographic studies demonstrated that the cats with HS had significantly greater LV wall thickness than those in the DM or healthy control group. Almost ¾ of the HS group (72%) had clinically significant LV hypertrophy (LV wall thickness > 6 mm), in contrast to 36% of the DM group and 21% of the control group. In the HS group, moreover, left atrial diameter was greater (median 16.6 mm; range 13.0-29.5 mm) than in the DM group (median 15.2 mm; range 10.2-21.3 mm) or the control group (median 14.0 mm; range 12.6-17.4 mm). Cats in both the HS and DM groups had more aortic insufficiency than the control cats. A larger number (27%) of the HS cats had reduced diastolic function compared to the DM group (13%) or the control group (6%). The cardiac biomarkers, NTproBNP and cardiac troponin 1, were not significantly different among the groups.
Of the 67 cats in the HS group, 9 cats received medical treatment (long-acting pasireotide; PAS group) and 20 underwent surgical hypophysectomy (HYP group). While the HYP group achieved statistically significant reductions in diastolic LV wall thickness and left atrial size, as well as improvements in diastolic function, the PAS group experienced a reduction in left atrial diameter only.
In the histopathological investigation portion of the study, pituitary gland histopathology was available for 16/21 of the HS group; 11 of these had an acidophil adenoma and 5 had acidophil hyperplasia; none had acidophil carcinoma. All 63 of the patients whose tissues were examined had cardiac myocyte hypertrophy, but severe myocyte hypertrophy was noted in some of the cats in the HCM and HS groups. Over 90% of the feline HS cardiac tissue samples demonstrated interstitial fibrosis, similar to the 85% incidence of this finding in humans with HS. Intramural arteriosclerosis was identified in about 50% of the HS cats, in contrast to about 22% of humans with HS, and inflammatory cell infiltrates were present in the hearts of approximately 40% of the HS cats, while this is found in 59% of humans with HS. Cardiac myocyte disarray is uncommon in both cats and humans with HS; this is a histopathologic hallmark of HCM and was found more frequently in in the HCM group than in the HS or control groups.
All cats with HS in this study also had DM. In contrast, only 15-35% of humans with HS also have DM. The non-acromegalic feline DM group evaluated in this study did not have clinically significant HCM, but the group size was small. Although progressive diastolic dysfunction has been reported in cats with DM, these cats did not have LV hypertrophy. The authors recommend that a study of a larger group of diabetic cats along with controls be performed to learn more about the possibility of diabetic cardiomyopathy in cats.
These researchers determined that feline HS is associated with LV hypertrophy, and this cardiomyopathy is reversible with hypophysectomy. Acromegalic cardiomyopathy in cats has marked similarities with human acromegalic cardiomyopathy in terms of clinical presentation, echocardiographic findings, and histopathology of pituitary and cardiac tissues. Future studies of disease characteristics and treatment modalities of HS in cats and humans is likely to be of benefit to both species. [PJS]
Dirtu AC, Niessen SJ, et al. Organohalogenated contaminants in domestic cats’ plasma in relation to spontaneous acromegaly and type 2 diabetes mellitus: a clue for endocrine disruption in humans? Environment International 2013;57-58:60-67.