Comparative Efficacy and Safety of Mycophenolate Mofetil and Azathioprine in Combination with Corticosteroids in the Treatment of Lymphocytic Myocarditis.

AIMS: This paper aimed to study the efficacy and safety of mycophenolate mofetil (MM) in combination with corticosteroids in the treatment of lymphocytic myocarditis (LM) when compared to the standard combination of corticosteroids and azathioprine. METHODS: The study included 50 adult patients (47.8 ± 10.8 y.o.) in a NYHA III functional class due to LM who were verified using endomyocardial biopsy. The main group included 29 patients who received MM at 2 g/day. The comparison group comprised 21 patients who received azathioprine at 150 [50; 150] mg/day. Both groups were administered with methylprednisolone. The average follow-up period was 30 [22; 35] months, but no less than 6 months. RESULTS: The groups were comparable in the baseline parameters and standard drug therapy. In both groups, there was a comparable significant increase in the ejection fraction (from 30.6 ± 7.7% to 44.0 ± 9.4% vs. 29.2 ± 7.7% to 46.2 ± 11.8%, p < 0.001), and a decrease in systolic pressure in the pulmonary artery and the dimensions of the left ventricle and atrium. The frequency of death was two (6.9%) and two (9.5%), transplantation was one (3.4%) and one (4.8%) patient and the "death + transplantation" endpoint was three (10.3%) and three (14.3%) without differences between the groups. The presence of the parvovirus B19 in the myocardium in 6/5 patients did not affect the results. The incidence of infectious complications was comparable. The most severe infectious complications were pneumonia and fatal purulent encephalitis (both cases in the azathioprine group), leptospirosis meningitis (in the mycophenolate mofetil group). CONCLUSIONS: In the patients with LM, the combination of corticosteroids with MM at a dose of 2 g/day was at least no less effective than with azathioprine. There was a tendency toward a better tolerance using MM.

Mixed-Etiology Restrictive Cardiomyopathy (Desminopathy and Hemochromatosis) with Complex Liver Lesions.

A 28 year-old male with restrictive cardiomyopathy (RCM) and endocardium thickening, conduction disorders, heart failure, and depressive disorder treated with paroxetine was admitted to the clinic. Blood tests revealed an increase in serum iron level, transferrin saturation percentage, and slightly elevated liver function tests. Sarcoidosis, storage diseases and Loeffler endocarditis were ruled out. Mutations in desmin (DES) and hemochromatosis gene (HFE1) were identified. Liver biopsy was obtained to verify the hemochromatosis, assess its possible contribution to the RCM progression and determine indications for treatment. Biopsy revealed signs of drug-induced injury, subcompensated heart failure, and hemosiderin accumulation. Thus, even if one obvious cause (desmin mutation) of RCM has been identified, other less likely causes should be taken into consideration.

Clinical Classification of Arrhythmogenic Right Ventricular Cardiomyopathy.

INTRODUCTION: Commonly accepted clinical classification of arrhythmogenic right ventricular cardiomyopathy (ARVC) is still not developed. OBJECTIVE: To study the clinical forms of ARVC. METHODS: Fifty-four patients (38.7 ± 14.1 years, 42.6% men) with ARVC. Follow-up period: 21 (6-60) months. All patients underwent electrocardiography, 24 h-Holter monitoring, echocardiography, and DNA diagnostic. Magnetic resonance imaging was performed in 49 patients. RESULTS: According to the features of clinical course of ARVC, 4 clinical forms were identified. (I) Latent arrhythmic form (n = 27) - frequent premature ventricular contractions and/or nonsustained ventricular tachycardia (VT) in the absence of sustained VT and syncope; characterized by absence of fatal arrhythmic events. (II) Manifested arrhythmic form (n = 11) - sustained VT/ventricular fibrillation; the high incidence of appropriate implantation of cardioverter-defibrillator (ICD) interventions (75%) registered. (III) ARVC with progressive chronic heart failure (CHF, n = 8) as the main manifestation of the disease; incidence of appropriate ICD interventions was 50%, mortality rate due to CHF was 25%. (IV) Combination of ARVC with left ventricular noncompaction (n = 8); characterized by mutations in desmosomal or sarcomere genes, aggressive ventricular arrhythmias, appropriate ICD interventions in 100% patients. Described 4 clinical forms are stable in time, do not transform into each other, and they are genetically determined. CONCLUSIONS: The described clinical forms of ARVC are determined by a combination of genetic and environmental factors and do not transform into each other. The proposed classification could be used in clinical practice to determine the range of diagnostic and therapeutic measures and to assess the prognosis of the disease in a particular patient.

Immunosuppressive therapy of biopsy proved immune-mediated lymphocytic myocarditis in the virus-negative and virus-positive patients.

PURPOSE: to study the effect of immunosupressive therapy (IST) in the virus-negative and virus-positive patients with immune-mediated myocarditis. METHODS: in 60 patients (45 male, 46.7 ± 11.8 years, mean LV EDD, 6.7 ± 0.7 cm, EF 26.2 ± 9.1%) active/borderline myocarditis was verified by endomyocardial biopsy (n = 38), intraoperative biopsy (n = 10), examination of explanted heart (n = 3) and autopsy (n = 9). Indications for IST determined based on histological, immune activity. The follow-up was 19.0 [7.25; 40.25] months. RESULTS: The viral genome in the myocardium was detected in 32 patients (V+ group), incl. parvovirus B19 in 23. The anti-heart antibody level was equally high in the V+ and V- patients. Antiviral therapy was administered in 24 patients. IST (in 22 V+ and 24 V- patients) include steroids (n = 40), hydroxychloroquine (n = 20), azathioprine (n = 21). The significant decrease of LV EDD (6.7 ± 0.7 to 6.4 ± 0.8), PAP (48.9 ± 15.5 to 39.4 ± 11.5 mm Hg, р<0,01), increase of EF (26.5 ± 0.9 to 36.0 ± 10.8), and lower lethality (23.9% and 64.3%; RR 0.37, 95% CI 0.19-0.71), p<0.01, were found only in IST group. Significant improvement due to IST were achieved not only in V-, but also in V+ patients. CONCLUSIONS: IST in patients with immune-mediated lymphocytic myocarditis is effective and is associated with lower lethality both in virus-negative and virus-positive patients.

Diagnostic Value of Different Noninvasive Criteria of Latent Myocarditis in Comparison with Myocardial Biopsy.

PURPOSE: The aim of this study was to quantify the value of various clinical, laboratory, and instrumental signs in the diagnosis of myocarditis in comparison with morphological studies of the myocardium. METHODS: In 100 patients (65 men, 44.7 ± 12.5 years old) with "idiopathic" arrhythmias (n = 20) and dilated cardiomyopathy (DCM; n = 80), we performed the following: 71 endomyocardial biopsies (EMB), 13 intraoperative biopsies, 5 studies of explanted hearts, and 11 autopsies with virus investigation (real-time PCR) of the blood and myocardium. Antiheart antibodies (AHA) were also measured as well as cardiac CT (n = 45), MRI (n = 25), and coronary angiography (n = 47). The comparison group included 50 patients (25 men, 53.7 ± 11.7 years old) with noninflammatory heart diseases who underwent open heart surgery. RESULTS: Active/borderline myocarditis was diagnosed in 76.0% of the study group and in 21.6% of patients in the comparison group (p < 0.001). The myocardial viral genome was observed more frequently in patients in the comparison group than in the study group (65.0 and 40.2%; p < 0.01). We evaluated the diagnostic value of noninvasive markers of myocarditis. The panel of AHA had the greatest importance in the identification of myocarditis: sensitivity was 81.5%, and the positive and negative predictive values were 75.0 and 60.5%. This defined the diagnostic value of noninvasive markers of myocarditis and established a diagnostic algorithm providing an individual assessment of the likelihood of myocarditis development. CONCLUSION: AHA have the greatest significance in the diagnosis of latent myocarditis in patients with "idiopathic" arrhythmias and DCM. The use of a complex of noninvasive criteria allows the probability of myocarditis to be estimated and the indications for EMB to be determined.

Dilated cardiomyopathy with severe arrhythmias in Emery-Dreifuss muscular dystrophy: from ablation to heart transplantation.

We present 38-years male patient. He has suffered from muscle weakness since 5 years. Arrhythmias appeared at the age of 32. In 37 years he had sick sinus syndrome, transient AV block II degree, paroxysmal atrial fibrillation, atrial flutter, ventricular arrhythmias. At this time, dilated cardiomyopathy was also detected. The evaluation revealed knees and elbows contractures, increased level of creatine kinase. The genetic testing revealed a frame shift deletion c.del619C in the emerin (EMD) gene and c.IVS4-13T> A in the lamin (LMNA) gene, and c.del619C deletion in the heterozygous state in a patient`s mother. Radiofrequency ablation of cavotricuspid isthmus, implantable cardioverter-defibrillator (ICD) implantation were performed. Heart transplantation was performed nine months later, due to severe heart failure and electrical storm. A morphological evaluation revealed sclerosis, atrophy and hypertrophy of cardiomyocytes. He underwent an induction therapy with (basiliximab) methylprednisolone, tacrolimus, mycophenolate after heart transplantation. During 40 months after transplantation, patient`s condition is satisfactory. CONCLUSION: heart failure in Emery-Dreifuss muscular dystrophy can progress quickly unless the previously stable condition. The use of correct regimens of immunosuppression therapy provides good long-term results of the heart transplantation.