Dilated cardiomyopathy (DCM) has been in the literature and news because of the recent opinion-based journal articles and public releases by regulatory agencies. DCM is commonly associated with a genetic predisposition in certain dog breeds and can also occur secondary to other diseases and nutritional deficiencies. Recent communications in veterinary journals have discussed a potential relationship between grain-free and/or novel protein diets to DCM, citing a subjective increase in DCM in dog breeds that are not known to have a genetic predisposition for the disease. This literature review describes clinical presentations of DCM, common sequelae, treatment and preventative measures, histopathologic features, and a discussion of the varied etiological origins of the disease. In addition, current literature limitations are addressed, in order to ascertain multiple variables leading to the development of DCM. Future studies are needed to evaluate one variable at a time and to minimize confounding variables and speculation. Furthermore, to prevent sampling bias with the current FDA reports, the veterinary community should be asked to provide information for all cases of DCM in dogs. This should include cases during the same time period, regardless of the practitioner's proposed etiology, due to no definitive association between diets with specific characteristics, such as, but not limited to, grain-free diets and those containing legumes, novel protein diets, and those produced by small manufacturers to DCM in dogs. In summary, in order to determine if certain ingredients, categories of diets, or manufacturing processes are related to an increased risk of DCM, further studies investigating these variables are necessary.

/pdf/review-of-canine-dilated-cardiomyopathy-in-the-wake-of-diet-4pt4fwvsis.pdf

Review of canine dilated cardiomyopathy in the wake of diet-associated concerns.

Purpose In this study, we aimed to investigate the relationship between hypothyroidism and sterile inflammation in rat heart tissue. Methods Groups; control group (fed with standard rat chow diet and tab water) and the hypothyroid group (fed with a standard rat chow diet and tap water containing 0.05% 6-n-propyl-2-thiouracil for 6-weeks). At the end of the experiment, histopathologic examination was performed. The T3, T4, TSH and myocardial malondialdehyde (MDA) measurements were performed with an ELISA kit. TUNEL assay was performed to demonstrate apoptosis. Sterile inflammation markers, caspase-1 and NLRP3, were investigated by immunohistochemistry and western blot. Results In histopathological examination, we observed leukocyte infiltration, myocardial atrophy, pyknotic nucleated cells and cytoplasmic vacuolization in hypothyroid group whereas the control group showed normal structure. MDA levels in myocardial tissue were significantly high in hypothyroid group when compared to the control group (P<0.05). Myocardial apoptosis increased in hypothyroid group when compared to the control group. NLRP3 and caspase-1 immunoreactivity was higher in the hypothyroid group. In ELISA results, we found significantly higher level of TSH and lower levels of T3 and T4 in hypothyroid group when compared to the control group. Conclusion Hypothyroidism increased oxidative stress, and caused inflammatory alterations in cardiac tissue. In addition, our study also suggested that thyroid hormone deficiency would increase the amounts of cardiac NLRP3 and caspase-1 protein, which indicates that hypothyroidism exerts its destructive effects through sterile inflammation. Elucidation of sterile inflammation-associated pathways may produce promising results in the treatment of hypothyroidism-induced cardiac damage.

Hypothyroidism increases expression of sterile inflammation proteins in rat heart tissue.

Dilated cardiomyopathy (DCM) is the most prevalent cardiomyopathy, typified by left ventricular dilation and systolic dysfunction. Many patients with DCM have altered thyroid status, especially lower levels of free triiodothyronine (T3) and elevated levels of thyroid-stimulating hormone. Moreover, growing evidence indicates that even subtle changes in thyroid status (especially low T3) are linked with a worse long-term prognosis and a higher risk of mortality. Notably, recent discoveries have shown that not only local myocardial thyroid hormones (THs) bioavailability could be diminished due to impaired expression of the activating deiodinase, but virtually all genes involved in TH biosynthesis are also expressed in the myocardium of DCM patients. Importantly, some studies have suggested beneficial effects of TH therapy in patients suffering from DCM. Our aim was to discuss new insights into the association between TH status and prognosis in DCM, abnormal expression of genes involved in the myocardial synthesis of TH in DCM, and the potential for TH use in the future treatment of DCM.

Thyroid Hormones-An Underestimated Player in Dilated Cardiomyopathy?

Background: Pediatricians and pediatric surgeons often face children with cardiomegaly and dilatative or hypertrophic cardiomyopathies presenting with or without symptoms. Some of these patients have already been diagnosed and received medication, and some present with completely unrelated pathologies. Methods: We performed a 4-year retrospective study on the causes and mechanisms of death of children with cardiac pathology who died outside the cardiology clinic of our hospital by studying the hospital charts and necropsy reports. All children who were in this situation in our hospital were included. Results: Most children in our study group were infants (81.82%), most were boys (81.82%), and in most cases, the cause or mechanism of death was unrelated to their heart condition, whether it had already been diagnosed or not (one case probably died as a result of a malignant ventricular arrhythmia). Additionally, 27.27% of children died as a consequence of bronchopneumonia, the same percentage died as a consequence of an acquired non-pulmonary disease or after surgery, and 18.18% died as a consequence of congenital malformations. Conclusions: Cardiac disease needs to be thoroughly investigated using multiple tools for all children presenting with heart failure symptoms, those with heart murmurs, and children scheduled for surgery of any type. The intensive care specialist and surgeon need to be aware of any heart pathology before non-cardiac surgical interventions.

/pdf/non-cardiac-cause-of-death-in-selected-group-children-with-3h0j759t.pdf

Non-Cardiac Cause of Death in Selected Group Children with Cardiac Pathology: A Retrospective Single Institute Study

CMAJ | January 9, 2023 | Volume 195 | Issue 1 © 2023 CMA Impact Inc. or its licensors A 45-year-old man presented to the general medicine clinic with a 2-week history of leg edema and dyspnea on exertion, including when walking up stairs. He had also noticed a new nonproductive cough. Five years before admission, his general practitioner had diagnosed hypothyroidism while ruling out secondary causes of dyslipidemia. He had been referred to our clinic, and we had diagnosed Hashimoto thyroiditis. His endocrinologist had treated him with 150 μg/d of levothyroxine; however, the patient was lost to follow-up 3 years later. He had no other relevant personal or family hist ory, including autoimmune or cardiovascular diseases. He had smoked 20 cigarettes per day for 25 years, reported not consuming alcohol or illicit substances, and worked as an interior decorator. He was not on any medications at the time of admission. On examination, the patient was conscious and alert, afebrile, slightly tachypneic (22 breaths/min), normotensive (116/88 mm Hg) and borderline tachycardic (100 beats/min). He had an oxygen saturation level of 99% on room air. On chest auscultation, we heard late inspiratory crackles in both lung fields and a third heart sound. He did not have raised jugular venous pressure. We observed generalized pitting edema without overlying skin changes in the face, hands and lower legs up to the lower calves (Figure 1). In addition, we observed delayed relaxation of the ankle jerk reflex (Woltman sign) (Appendix 1, Video 1A, available at www.cmaj.ca/lookup/doi/10.1503/cmaj.220861/tab-related -content). Laboratory investigations showed a leukocyte count of 7200 (normal 3300–8600) cells/μL, hemoglobin level of 13.6 (normal 13.7–16.8) g/dL, creatine phosphokinase level of 786 (normal 59–248) U/L, creatine phosphokinase MB level of 6 (normal < 12.0) U/L, albumin level of 3.7 (normal 4.1–5.1) g/dL and brain natriuretic peptide level of 1140 (normal < 18.4) pg/mL. His thyroid profile included a thyroid-stimulating hormone level of 196.2 (normal 0.27–4.2) mIU/L, free thyroxine level of 1.80 (normal 11.58–23.17) pmol/L and free triiodothyronine level of 0.74 (normal 3.70–6.93) pmol/L. An electrocardiogram (ECG) showed slightly low QRS voltage in the limb leads and a biphasic P-wave in lead V1 (Figure 2). A chest radiograph showed cardiomegaly and pulmonary edema (Figure 3A). An ECG showed left ventricular global hypokinesis with a left ventricular ejection fraction of 28.4%, left ventricular enlargement with an end-diastolic diameter of 58.5 mm and an estimated right ventricular systolic pressure of 70.7 mm Hg. Cardiac magnetic resonance imaging (MRI) also showed left ventricular contractile dysfunction (Appendix 2, Video 2A and 2B, available at www.cmaj.ca/lookup/doi/10.1503/cmaj.220861/ tab-related-content), with a left ventricular ejection fraction of 22.5% and right ventricular ejection fraction of 15.3%. However, we did not observe any late gadolinium enhancement or native T1 relaxation time changes on T1 mapping, with no evidence of myocardial edema and fibrosis. After discussions with the cardiology and endocrinology teams, and based on our patient’s emergent signs and symptoms, nonspecific ECG changes, biochemical evidence of severe hypothyroidism and absence of late gadolinium enhancement on cardiac MRI, we Practice | Cases CPD

/pdf/generalized-pitting-edema-in-a-patient-with-dilated-25kzxvl3.pdf

Generalized pitting edema in a patient with dilated cardiomyopathy secondary to hypothyroidism

Dilated cardiomyopathy (DCM) is an idiopathic condition that results from impaired ventricular systolic function. Thyroid diseases have been known to cause myriad changes in the structure and function of the heart. Diastolic dysfunction is a common abnormality reported in hypothyroidism. However, hypothyroidism-induced DCM and systolic dysfunction is an uncommon phenomenon, especially as the initial presenting manifestation of hypothyroidism. The current article describes the case of a young female who presented with symptoms of heart failure and was diagnosed as having DCM as echocardiography revealed left ventricular global hypokinesia and severely depressed systolic function. Thyroid profile revealed a grossly elevated thyroid-stimulating hormone (TSH) value of 313 μIU/ml; free thyroxine (fT4) was 0.220 ng/dl. The present case presented with DCM as the initial presentation of hypothyroidism and improved significantly after five months of levothyroxine replacement therapy.

A Dua

Papers

Hypothyroidism-induced reversible dilated cardiomyopathy.