Pruritogenic molecules in the skin of patients with dermatomyositis.

Introduction: Pruritus is a common excruciating symptom in systemic autoimmune diseases such as dermatomyositis (DM) but the pathogenesis is not fully understood. We intended to investigate the targeted expression analysis of candidate molecules involved in the development of pruritus in lesional vs. non-lesional skin samples of patients affected with active DM. We looked for correlations between the investigated pruriceptive signaling molecules, disease activity, and itching sensation of DM patients. Methods: Interleukins (IL-33 and IL-6), tumor necrosis factor α (TNF-α), peroxisome proliferator-activated receptor γ (PPAR-γ), and ion channels belonging to the transient receptor potential (TRP) family were analyzed. The expression of TNF-α, PPAR-γ, IL-33, IL-6, and TRP channels in lesional DM skin was evaluated by RT-qPCR and immunohistochemistry and was compared with non-lesional DM skin samples. Pruritus, disease activity, and damage of DM were evaluated by the 5-D itch scale and Cutaneous Dermatomyositis Disease Area and Severity Index (CDASI), respectively. Statistical analysis was performed with IBM SPSS 28 software. Results: A total of 17 active DM patients participated in the study. We could show that the itching score was positively correlated with the CDASI activity score (Kendall's tau-b = 0.571; p = 0.003). TNF-α gene expression was significantly higher in lesional DM skin than in non-lesional DM skin (p = 0.009) and differed in the subgroups of patients with different itch intensities (p = 0.038). The mRNA expression of lesional IL-6 correlated positively with 5-D itch and CDASI activity score (Kendall's tau-b = 0.585; p = 0.008 and 0.45; p = 0.013, respectively). TRPV4 expressions were positively correlated with CDASI damage score (Kendall's tau-b = 0.626; p < 0.001), but the mRNA expressions of the TRP family, PPAR-γ, IL-6, and IL-33 were not different in lesional and non-lesional samples. Immunohistochemistry analysis did not find significant alterations in the expressions of TNF-α, PPAR-γ, IL-6, and IL-33 in lesional and non-lesional regions. Discussion: Our results argue that cutaneous disease activity, TNF-α, and IL-6 might play a central role in DM-associated itch, while TRPV4 plays a central role in tissue regeneration.

Incidence, features, and outcome of disease relapse after COVID-19 vaccination in patients with idiopathic inflammatory myopathies.

INTRODUCTION/AIMS: Vaccination against coronavirus disease 2019 (COVID-19) is relatively safe in patients with idiopathic inflammatory myopathies (IIM); however, myositis flares following vaccination have been poorly studied. We aimed to evaluate the frequency, features, and outcomes of disease relapses in patients with IIM following COVID-19 vaccination. METHODS: A cohort of 176 IIM patients were interviewed after the third wave of the COVID-19 pandemic and followed prospectively. Relapses were determined using the disease state criteria and the outcome of the flares with myositis response criteria, calculating the total improvement score (TIS). RESULTS: A total of 146 (82.9%) patients received a vaccination, 17/146 (11.6%) patients had a relapse within 3 mo, and 13/146 (8.9%) patients within 1 mo. The relapse rate of unvaccinated patients was 3.3%. Three months after the post-vaccination relapses, 70.6% of the patients (12/17) achieved an improvement of disease activity (average TIS score: 30 ± 15.81; seven minor, five moderate, and zero major improvements). Six months after flares improvement was detected in 15/17(88.2%) of relapsed patients (average TIS score: 43.1 ± 19.53; 3 minimal, 8 moderate, and 4 major). Forward stepwise logistic regression analysis revealed that the active state of myositis at the time of injection (p < .0001; odds ratio, 33; confidence interval, 9-120) was significantly associated with the occurrence of a relapse. DISCUSSION: A minority of the vaccinated IIM patients had a confirmed disease flare after COVID-19 vaccination and the majority of the relapses improved after individualized treatment. An active disease state at the time of vaccination probably contributes to the increased risk of a post vaccination myositis flare.

Novel aspects of muscle involvement in immune-mediated inflammatory arthropathies and connective tissue diseases.

Myalgia, myopathy and myositis are the most important types of muscle impairment in immune-mediated inflammatory arthropathies and connective tissue diseases. Multiple pathogenetic and histological changes occur in the striated muscles of these patients. Clinically, the most important muscle involvement is the one that causes complaints to the patients. In everyday practice, insidious symptoms present a serious problem for the clinician; in many cases, it is difficult to decide when and how to treat the muscle symptoms that are often present only subclinically. In this work, authors review the international literature on the types of muscle problems in autoimmune diseases. In scleroderma histopathological picture of muscle shows a very heterogeneous picture, necrosis and atrophy are common. In rheumatoid arthritis and systemic lupus erythematosus, myopathy is a much less defined concept, further studies are needed to describe it. According to our view, overlap myositis should be recognized as a separate entity, preferably with distinct histological and serological characteristics. More studies are needed to describe muscle impairment in autoimmune diseases which may help to explore this topic more in depth and be of clinical use.

The effect of COVID-19 pandemic on idiopathic inflammatory myositis patients: a single centre experience.

OBJECTIVES: Pandemic caused by coronavirus disease (COVID-19) determines the life of clinicians and patients since 2 years. We have a lot of information about disease course, treatment and protection against virus, but less on the prognosis of infection in patients with idiopathic inflammatory myopathies (IIM). Also few data are available on triggered humoral response and side effects after vaccination. METHODS: Our goal was to assess by a retrospective cross-sectional study the above data in our cohort (176 IIM patients) by identifying COVID-19 positive patients and follow disease course. Incidence and complications of vaccination were determined by questionnaires. 101 patients volunteered for complex blood test. RESULTS: By June 1st, 2021 significantly higher incidence of COVID 19 infections (34.7%) were identified comparing to the national prevalence (8.2%). A third of these infections occurred asymptomatically or mild. Patients requiring hospitalisation had a significantly longer disease duration and a higher incidence of anti-Jo-1 antibody. All patients infected by COVID-19 became seropositive regardless the immunosuppressive therapy or symptoms severity. 54.3% of the patients received anti-COVID-19 vaccine. 72.3% of patients became seropositive after vaccination. Higher antibody titer against spike protein was detected after Pfizer-BioNTech vaccination compared to others. Patients receiving steroid therapy had decreased post-vaccination antibody response compared to those without steroid treatment. No major post-vaccination infection was observed. CONCLUSIONS: Based on our results, myositis may be associated with an increased risk of COVID-19 infection. Independent risk factor for hospitalisation are longer disease duration and anti-Jo1 positivity. Anti-SARS-CoV2 vaccines seem safe and tolerable and strongly recommended for that population.

Clinical, Serological, and Genetic Characteristics of a Hungarian Myositis-Scleroderma Overlap Cohort.

Overlap myositis is a distinct subgroup of idiopathic inflammatory myositis (IIM) with various clinical phenotypes. The aim of this study was to determine the clinical, serological, and genetic features of systemic sclerosis (SSc)-IIM overlap patients. It was a retrospective study using clinical database of 39 patients, fulfilling both the criteria of SSc and IIM. 56.4% of the patients had limited cutaneous, 43.6% had diffuse cutaneous SSc, whereas 7.7% of the patients had dermatomyositis and 92.3% polymyositis. The two diseases occurred simultaneously in 58.97%, while 10.26% in myositis and 30.77% in scleroderma were initially diagnosed. The frequencies of organ involvement were interstitial lung disease 71.8%, dysphagia 66.7%, cardiac involvement 41%, pulmonary arterial hypertension (PAH) 30.8%, and renal involvement 12.8%, respectively. The presence of human leukocyte antigen (HLA) - DRB1∗03 and DQA1∗051∗01 alleles were significantly higher in the overlap patients than in healthy controls (82.35% vs. 27.54%; p < 0.0001 and 88.24% vs. 30.16; p < 0.0001). Certain clinical parameters, such as fever at diagnosis (41.67% vs. 7.41%, p = 0.0046), cardiac involvement (83.33% vs. 22.22%, p = 0.0008), subcutaneous calcinosis (41.66 vs. 11.11, p = 0.01146), and claw hand deformity (25% vs. 11.11%, p = 0.00016) were significantly associated with the presence of PAH. Upon comparison, the overlap patients and anti-Jo-1 positive antisynthetase patients showed similarities in terms of genetic results and major clinical features; however, SSc-IIM overlap patients could be distinguished with higher erythrocyte sedimentation rate (ESR) level, more frequent presence of Raynaud's phenomenon (p < 0.0001; OR: 20.00), dysphagia (p < 0.0001; OR: 15.63), and infrequent livedo reticularis (p < 0.01; OR: 0.11). SSc-IIM overlap myositis is a unique group within IIM-s possessing characteristic clinical features.

The risk of fracture and prevalence of osteoporosis is elevated in patients with idiopathic inflammatory myopathies: cross-sectional study from a single Hungarian center.

BACKGROUND: The prevalence of osteoporosis and risk of fractures is elevated in rheumatoid arthritis (RA), but we have limited information about the bone mineral density (BMD) and fracture risk in patients with inflammatory myopathies. We intended to ascertain and compare fracture risk, bone mineral density and the prevalence of vertebral fractures in patients with inflammatory myositis and rheumatoid arthritis and to assess the effect of prevalent fractures on the quality of life and functional capacity. METHODS: Fifty-two patients with myositis and 43 patients with rheumatoid arthritis were included in the study. Fracture Risk was determined using FRAX® Calculation Tool developed by the University of Sheffield. Dual energy X-ray absorptiometry and bidirectional thoracolumbar radiographs were performed to assess BMD and vertebral fractures. Quality of life was measured with Short Form-36 (SF-36) and physical function assessment was performed using Health Assessment Questionnaire (HAQ). RESULTS: We found a significantly elevated fracture risk in RA as compared to myositis patients if the risk assessment was performed without the inclusion of the BMD results. If BMD results and glucocorticoid dose adjustment were taken into account, the differences in fracture risk were no longer significant. The prevalence of osteoporosis was found to be significantly higher in the myositis group (7% vs. 13.5%, p: 0.045), but the fracture prevalence was similar in the two groups (75% vs. 68%). The fracture rates were independently associated with age in the myositis group, and with lower BMD results in the RA patients. The number of prevalent fractures was significantly correlated to poorer physical function in both groups, and poorer health status in the myositis group, but not in the RA group. CONCLUSIONS: Our findings suggest that inflammatory myopathies carry significantly elevated risks for osteoporosis and fractures. These higher risks are comparable to ones detected with RA in studies and strongly affect the physical function and quality of life of patients. Therefore further efforts are required to make the fracture risk assessment reliable and to facilitate the use of early preventive treatments.

Retrospective Analysis of Cancer-Associated Myositis Patients over the Past 3 Decades in a Hungarian Myositis Cohort.

Association between cancer and myositis has been extensively reported and malignancy is a potentially life-threating complication in myositis. In this retrospective study authors give an overview of Hungarian cancer-associated myositis (CAM) patients treated at a single centre managing 450 myositis patients. All patients were diagnosed according to Bohan and Peter. Statistical analysis of disease onset, age, sex, muscle, skin and extramuscular symptoms, muscle enzymes, presence of antibodies, treatment and prognosis was performed. 43 patients could be considered as having CAM. 83.72% had cancer within one year of diagnosis of myositis. Most common localizations were ductal carcinoma of breast and adenocarcinoma of lung. Significant differences were observed between CAM and the non-CAM control patients: DM:PM ratio was 2.31:1 vs. 0.87:1, respectively (p = 0.029), age at diagnosis was 56.60 ± 12.79 vs. 38.88 ± 10.88 years, respectively (p < 0.001). Tumour-treatment was the following: surgical removal in 55.81%, chemotherapy in 51.1%, radiotherapy in 39.53%, hormone treatment in 18.6%, combination therapy in 51.16% of patients. Muscle enzyme levels of patients undergoing surgery were significantly reduced after intervention. 36 patients died (83.72%); 25 DM (83.33%) and 11 PM patients (84.62%); 5 years survival was 15.4% for PM and 27.5% for DM. This study demonstrates that DM, distal muscle weakness, asymmetric Raynaud's phenomenon, older age, ANA-negativity are risk factors for developing malignancy and polymyositis patients have less chance of long-lasting survival. It is very important to think about cancer and follow every single myositis patient in the clinical routine because survival rate of CAM is very poor.

Dysregulated expression profile of myomiRs in the skeletal muscle of patients with polymyositis.

MicroRNA (miRNA) research has intensively developed over the past decade. Characterization of dysregulated miRNA expression profiles could give a better understanding of the development of pathological conditions and clinical disorders, such as autoimmune diseases with polygenic etiology, including idiopathic inflammatory myopathies (IIMs). IIMs are a group of rare autoimmune disorders characterized by skeletal weakness and inflammation. Polymyositis (PM) is one of the conditions of autoimmune myopathies with proximal skeletal muscle weakness. A novel group of miRNAs, known as myomiRs are described as striated muscle-specific or muscle-enriched miRNAs. They are involved in myoblast proliferation/differentiation as well as muscle regeneration. To determine the role of myomiRs in the development and progression of PM, we performed an initial skeletal muscle miRNA profiling using microarray technique at diagnosis. The aim of the study was to examine myomiRs expression profile in patients with PM in order to remark the association between the dysregulated myomiRs' expression and the development of the disease. As a results of microarray investigation, most of the myomiRs showed altered expression patterns in the muscle samples of PM patients compared to controls. These results suggest that myomiRs, especially miR-1, miR-133a, miR-208b, miR-486, and miR-499 function in a network, and are associated with the development of PM.

Effect of Genetic and Laboratory Findings on Clinical Course of Antisynthetase Syndrome in a Hungarian Cohort.

The aim of this study was to determine the clinical, serological, and genetic features of anti-Jo-1 positive antisynthetase patients followed by a Hungarian single centre to identify prognostic markers, which can predict disease phenotypes and disease progression. It was a retrospective study using clinical database of 49 anti-Jo-1 positive patients. 100% of patients exhibited myositis, 73% interstitial lung disease, 88% arthritis, 65% Raynaud's phenomenon, 43% fever, 33% mechanic's hand, and 12% dysphagia. We could detect significant correlation between anti-Jo-1 titer and the CK and CRP levels at disease onset and during disease course. HLA DRB1⁎03 positivity was present in 68.96% of patients, where the CK level at diagnosis was significantly lower compared to the HLA DRB1⁎03 negative patients. HLA DQA1⁎0501-DQB1⁎0201 haplotype was found in 58.62% of patients, but no significant correlation was found regarding any clinical or laboratory features. Higher CRP, ESR level, RF positivity, and the presence of fever or vasculitic skin lesions at the time of diagnosis indicated a higher steroid demand and the administration of higher number of immunosuppressants during the follow-up within anti-Jo-1 positive patients. The organ involvement of the disease was not different in HLA-DRB1⁎0301 positive or negative patients who were positive to the anti-Jo-1 antibody; however, initial CK level was lower in HLA-DRB1⁎0301 positive patients. Distinct laboratory and clinical parameters at diagnosis could be considered as prognostic markers.

[Clinical features and therapeutic response of our anti-SRP positive patients with myositis]. / Anti-SRP-pozitív myositises betegeink klinikai sajátosságai és terápiára adott válaszuk.

INTRODUCTION: Idiopathic inflammatory myopathies are a group of clinically heterogeneous diseases, which have been classified by myositis specific antibodies recently. The anti-SRP positive subset of this group is characterized by more severe clinical prognosis than other myositis specific antibody positive types. AIM: Our goal was to compare 16 anti-SRP positive patients in the Division of Clinical Immunology, Department of Internal Medicine, University of Debrecen with 16 antibody negative ones. METHOD: Muscle strength validated in both groups by the manual muscle test proved to be significantly decreased both before and after therapy (χ2 = 0.006 and 0.019) in the anti-SRP positive group. RESULTS: Muscle-specific inflammatory laboratory parameters showed significant difference only in case of LDH-levels after therapy. Both groups showed good clinical response to first line steroid treatment, yet the significantly higher rate of second line administration suggests worse therapeutic response of the antibody positive group. CONCLUSION: Based on these facts we determined poor clinical prognosis and therapeutic response of the anti-SRP positive group. Orv Hetil. 2017; 158(35): 1382-1389.

Pharmacological management of dermatomyositis.

INTRODUCTION: Dermatomyositis is a rare heterogeneous systemic autoimmune disease with multiple organ involvement which can result in significant disability and mortality. Despite the lack of placebo-controlled trials, glucocorticoids are considered to be the mainstay of initial management. Treatment strategies are mainly based on uncontrolled studies, evidence based guidelines for treatments do not exist. Areas covered: This review provides an overview of the currently available pharmacological treatments in the field of dermatomyositis including conventional immunosuppressants, biologics and topical agents. The role of antibodies in different treatment responses of dermatomyositis related clinicoserological syndromes is also discussed. A PubMed search was performed in order to find relevant literature for this review. Expert commentary: Early recognition and intervention is essential to ameliorate disease outcome. Determination of antibodies provide a useful key in diagnosis, clinical manifestations, malignancy, prognosis, and treatment response and may lead to wider acceptance of personalized medicine. Corticosteroids with adjunctive steroid-sparing immunosuppressive therapies are recommended to treat disease activity, prevent mortality, and reduce long-term disability. Combinations of second-line therapies or newer third-line therapies are used in severe, refractory, or corticosteroid-dependent diseases. Further research is required to assess the role of new therapies.

[The shades of anti-Jo1 positive antisynthetase syndrome in a Hungarian cohort]. / Az anti-Jo-1-pozitív antiszintetáz szindróma jellegzetességei gondozott betegeink alapján.

INTRODUCTION: In idiopathic inflammatory myopathies, the presence of anti-Jo-1 antibody defines a distinct clinical phenotype (myositis, arthritis, interstitial lung disease, Raynaud's phenomenon fever, mechanic's hands), called antisynthetase syndrome. AIM: To determine the demographic data as well as clinical, laboratory and terapeutical features of anti-Jo1 positive patients, followed by the department of the authors. METHOD: The medical records of 49 consecutive anti-Jo1 patients were reviewed. RESULTS: Demographic and clinical results were very similar to those published by other centers. Significant correlation was found between the anti-Jo-1 titer and the creatine kinase and C-reactive protein levels. Distinct laboratory results measured at the time of diagnosis of the disease (C-reactive protein, antigen A associated with Sjogren's syndrome, positive rheumatoid factor), and the presence of certain clinical symptoms (fever, vasculitic skin) may indicate a worse prognosis within the antisyntetase positive patient group. CONCLUSION: In the cases above more agressive immunosuppressive therapy may be required.

[Comparison of clinical characteristics and laboratory parameters of patients with dermatomyositis-specific autoantibodies and autoantibody-negative patients]. / Dermatomyositis-specifikus autoantitesttel rendelkezo és autoantitest-negatív betegeink klinikai jellemzoinek és laboratóriumi paramétereinek összehasonlítása.

INTRODUCTION: Myositis is an autoimmune disease characterised by proximal muscle weakness. AIM: The aim of the authors was to determine the frequency of dermatomyositis-specific autoantibodies (anti-Mi-2, anti-transcriptional intermediary factor 1 gamma, anti-nuclear matrix protein 2, anti-small ubiquitin-like modifier activating enzyme, anti-melanoma differentiation-associated gene) in a Hungarian myositis population and to compare the clinical features with the characteristics of patients without myositis-specific antibodies. METHOD: Antibodies were detected using immunoblot and immunoprecipitation. RESULTS: Of the 330 patients with myositis, 48 patients showed dermatomyositis-specific antibody positivity. The frequency of antibodies in these patients was lower than those published in literature Retrospective analysis of clinical findings and medical history revealed that patients with dermatomyositis-specific autoantibody had more severe muscle weakness and severe skin lesions at the beginning of the disease. CONCLUSIONS: Antibodies seem to be useful markers for distinct clinical subsets, for predicting the prognosis of myositis and the effectiveness of the therapy.

[Inclusion body myositis]. / Zárványtestes myositis.

The idiopathic inflammatory myopathies are systemic, chronic autoimmune diseases characterized by proximal symmetrical muscle weakness. One of the main diseases in this group is inclusion body myositis (IBM), an underdiagnosed, progressive muscle disease characteristically affecting the middle-aged and older population. It has a slow, relentlessly progressive course. The precise pathogenesis of the disease remains unknown. In most of the cases it is diagnosed a few years after the appearance of the first symptoms. The muscle biopsy typically shows endomysial inflammation, with invasion of mononuclear cells into the non-necrotic fibers, and also rimmed vacuoles. It appers, that both inflammation and degeneration are present at the onset of the disease. Our aim is to raise awareness about this disease which leads to severe disability, with clinicopathological case presentations and literature overview, emphasizing the importance of collaboration between the clinician and the neuropathologist. No effective therapy is currently available but the rapid diagnosis is essential to slow disease progression. Although this is a relatively rare disease, patients are presenting not only in immunology outpatient clinics; our reports aims to raise awareness and facilitate accurate early diagnosis of IBM.

Vitamin D receptor gene polymorphisms and haplotypes in Hungarian patients with idiopathic inflammatory myopathy.

Idiopathic inflammatory myopathies are autoimmune diseases characterized by symmetrical proximal muscle weakness. Our aim was to identify a correlation between VDR polymorphisms or haplotypes and myositis. We studied VDR-BsmI, VDR-ApaI, VDR-TaqI, and VDR-FokI polymorphisms and haplotypes in 89 Hungarian poly-/dermatomyositis patients (69 females) and 93 controls (52 females). We did not obtain any significant differences for VDR-FokI, BsmI, ApaI, and TaqI genotypes and allele frequencies between patients with myositis and healthy individuals. There was no association of VDR polymorphisms with clinical manifestations and laboratory profiles in myositis patients. Men with myositis had a significantly different distribution of BB, Bb, and bb genotypes than female patients, control male individuals, and the entire control group. Distribution of TT, Tt, and tt genotypes was significantly different in males than in females in patient group. According to four-marker haplotype prevalence, frequencies of sixteen possible haplotypes showed significant differences between patient and control groups. The three most frequent haplotypes in patients were the fbAt, FBaT, and fbAT. Our findings may reveal that there is a significant association: Bb and Tt genotypes can be associated with myositis in the Hungarian population we studied. We underline the importance of our result in the estimated prevalence of four-marker haplotypes.

Inclusion body myositis - pathomechanism and lessons from genetics.

Inclusion body myositis is a rare, late-onset myopathy. Both inflammatory and myodegenerative features play an important role in their pathogenesis. Overlapping clinicopathological entities are the familial inclusion body myopathies with or without dementia. These myopathies share several clinical and pathological features with the sporadic inflammatory disease. Therefore, better understanding of the genetic basis and pathomechanism of these rare familial cases may advance our knowledge and enable more effective treatment options in sporadic IBM, which is currently considered a relentlessly progressive incurable disease.

Echocardiographic abnormalities in new-onset polymyositis/dermatomyositis.

OBJECTIVE: To identify early echocardiographic abnormalities at the time of diagnosis of polymyositis (PM) and dermatomyositis (DM) and follow the echocardiographic findings during the first 3 months of therapy. METHODS: We included 30 PM/DM patients (23/7) with a mean age of 42.3 ± 1.6 years and without cardiovascular symptoms. Age-matched healthy patients served as controls. Clinical characteristics were recorded. Traditional echocardiography and tissue Doppler imaging (TDI) were performed to measure systolic [ejection fraction, right ventricular fractional area change (RV FAC), lateral and tricuspid annulus s velocities] and diastolic echocardiographic variables (mitral inflow velocities: E, A; deceleration time: DT; lateral and tricuspid annulus e', a' velocities, lateral E/e'). RESULTS: The left and right ventricular systolic dysfunction detected by TDI at the time of the PM/DM diagnosis improved, and characteristic values at the end of the followup period were comparable to those of the controls (lateral s: 10.6 ± 0.2, 8.7 ± 0.4, 9.6 ± 0.3, 11.3 ± 0.2 cm/s; RV FAC: 45.2 ± 2.3, 36.9 ± 1.5, 42.2 ± 1.3, 46.9 ± 1.2%; tricuspid s: 13.3 ± 0.2, 9.5 ± 0.4, 10.3 ± 0.3, 11.6 ± 0.5 cm/s; control, 0, 1, and 3 mos, respectively). Measurements indicated the development of diastolic dysfunction at 3 mos (E/A: 1.4 ± 0.1, 1.29 ± 0.05, 1.03 ± 0.05, 0.92 ± 0.05; DT: 148.6 ± 3.6, 157.3 ± 5.7, 168.3 ± 6.0, 184.3 ± 6.2 ms; lateral e': 12.8 ± 0.3, 12.1 ± 0.5, 10.2 ± 0.6, 10.8 ± 0.8 cm/s; E/e': 5.6 ± 0.1, 5.0 ± 0.22, 6.92 ± 0.46, 7.64 ± 0.47; control, 0, 1, and 3 mos, respectively). CONCLUSION: TDI is a useful method to detect early cardiac abnormalities complementing the conventional echocardiographic measurements. LV and RV systolic dysfunction found in the acute phase significantly improved during the first 3 months of therapy; however, deterioration of diastolic dysfunction was also observed.