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Recurrent NSTE-ACS in a Female Patient with Progressive Myocardial Dysfunction

The Clinical Case of the Month: May 2009

Case Presentation:

We present the case of a 44-year-old woman with diabetes mellitus, which has been treated with insulin for 10 years.
Myocardial Disease

The patient is after strumectomy due to nodular goiter treated substitutionally with 1-thyroxin, reports dyspnea for the last 6 months, limited effort tolerance and chest discomfort. On admission ECG revealed sinus rhythm (65’) and left bundle branch block (QRS=140 ms).

Echocardiography revealed the size of the heart cavities within the normal range, though at the upper limit, generalized hypokinesis and left ventricle ejection fraction at 51%. Coronary arteries assessed in coronarography were found normal with a slower flow. The patient had an elevated level of Troponin I to 0.69 ng/ml (N: 0,00 – 0,10 ng/ml) and CK-MB activity to 30.7 U/L (N: 0 – 6 U/L). Thyroid stimulating hormone (TSH) was normal 2.3 uIU/mL (N: 0.4 – 4.0 uIU/mL), and hemoglobin A1C was significantly elevated -7.8%.

Aspirin at a dose of 75 mg, angiotensin-converting enzyme inhibitor (ACE-I) and simvastatin were introduced. The dose of insulin was modified. Despite systematic and better-controlled pharmacotherapy, dyspnea and chest discomfort recurred.

Within the next two years the patient was hospitalized several times due to the exacerbation of the above-mentioned complaint and recurrent pulmonary edema. Lab tests revealed repeatedly increased Troponin I levels (0.12 – 0.69 ng/ml) and increased CK-MB activity (23.4 – 72.1 U/L).

Because of the symptoms and increased Troponin I levels a check-up coronarography was performed after one year. Coronary arteries were found normal. Echocardiography revealed left ventricle slightly bigger, decreasing left ventricle ejection fraction – 45% and mitral incompetence (++). The patient was discharged with recommended standard treatment with aspirin, ACE-I and statin (simvastatin at 20 mg/d), along with insulin and l-thyroxin. Despite systematic treatment complaints recurred.

Question1: Do you think the patient should undergo endomyocardial biopsy? If she were your patient, would you do it?

Soon the patient was again hospitalized in the Institute of Cardiology due to exacerbated complaints accompanied by an increase Troponin I level (0.18 ng/ml). Left bundle branch block in ECG. Echocardiography was similar as examination a year before. Tests for autoimmune diseases were performed. IgA class anti-endomysial antibodies were identified; positive test, very high titer (1:5120). Gastroduodenoscopy with the small intestine biopsy was done. The examination revealed grade IV villous atrophy as well as the small intestine lamina propria and endothelium lymphocytosis. The diagnosis of celiac disease was based on the laboratory and biopsy findings. Gluten-free diet was introduced.

Question 2: Would you treat the patient with steroids ?

General remarks:
Acute coronary syndromes (ACS) are most commonly associated with severe lesions in coronary arteries. Normal coronary arteries are found in 1-8.5% of ACS patients [1-3]. Only in one-third of these patients with normal coronary arteries could potential mechanisms leading to ACS be detected. They include vasomotion disorders, coagulation disorders, inflammation factors or emotional distress.
Celiac disease is a common autoimmune disease with estimates that the disease prevalence is up to 1% in the general population [4].

Celiac disease in children usually has the form of a malabsorption syndrome, but in adults, the manifestations may be scarce, and then it is harder to diagnose. Our 44-year-old female patient was diagnosed because of the physician’s increased awareness of the co-occurrence of autoimmune diseases in patients with endocrine disorders, namely diabetes mellitus and hypothyroidism. The prevalence of celiac disease among patients with insulin-dependent diabetes mellitus and autoimmune thyroid disease has been reported to be between 2-5% [5].

Celiac disease results from permanent intolerance to gliadin, the main fraction of gluten. Gliadin, playing the role of antigen, forms immunological complexes in the intestinal mucosa, which results in mucosal inflammation, crypt hyperplasia and villous atrophy. The performance of IgA antibody testing, either with anti-endomysial or anti-tissue transglutaminase antibodies, is recommended for the diagnosis of celiac disease.

Although there are few case reports on an association between celiac disease and ACS [6,7], a population-based study did not show a higher prevalence of myocardial infarction in patients with celiac disease [8]. It may be linked with protective factors like lower serum cholesterol levels and lower blood pressure in patients with celiac disease [4,8].

Therefore, the presence of recurrent ACS with normal coronary angiography in our patient could mimic autoimmune myocarditis. In fact, celiac disease has been reported to appear with such comorbidities as autoimmunological myocarditis, dilated cardiomyopathy and heart failure [9-12]. Observed dyspneic episodes and recurrent pulmonary edema could be the result of the predominant left ventricle diastolic dysfunction in the patient with mild mitral incompetence. Co-occurrence of diabetes mellitus and thyroid disease could contribute to the clinical manifestation. Several studies have demonstrated evidence for left ventricular diastolic dysfunction in patients with diabetes mellitus independently of coronary artery disease [13,14]. Patients with hypothyroidism have a coronary endothelial dysfunction, which improves during l-thyroxin treatment [15,16].

In summary, in patients with recurrent unexplained ACS or heart failure symptoms who have normal coronary angiography and co-occurrence of diabetes mellitus and hypothyroidism, screening for celiac disease may be mandatory.

Do you think the patient should undergo endomyocardial biopsy? If she were your patient, would you do it?

Recurrent ACS is not an indication for endomyocardial biopsy [17]. However, in this patient, ACS could be a mask of recurrent “smoldering” autoimmune myocarditis. Furthermore, endomyocardial biopsy should be considered in patients with unexplained chronic heart failure and persistent cardiac dysfunction [18]. We have not performed the procedure, however, with last hospitalization, we were just about to do it, but with positive results of immunological studies we decided against doing endomyocardial biopsy in the patient.

Question 2.
Would you treat the patient with steroids ?

Recurrent ACSs in our patient subsided once gluten-free diet was introduced. The treatment effectiveness was confirmed by a significant anti-endomysial antibody titre drop (from 1:5120 to 1:40). A beneficial effect of gluten-free diet in patients with autoimmunological myocarditis and dilated cardiomyopathy has been reported before [10,11,19].

Introducing a gluten-free diet in our patient fully eliminated coronary manifestations, and in this way steroids were not considered at all. In one-year follow-up, also troponin was found to have normalized. This finding might suggest that eliminating one additional immunological factor in the patient already treated with statin and angiotensin convertase inhibitor resulted in a significant improvement in coronary microcirculation functioning.

Notes to editor

By Ewa Podolecka, MD, Zofia T. Bilinska, MD, PhD, Institute of Cardiology, Warsaw, Poland
The content of this article reflects the personal opinion of the author/s and is not necessarily the official position of the European Society of Cardiology.

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