Randomized, Placebo-Controlled Study for Immunosuppressive Treatment of Inflammatory Dilated Cardiomyopathy

Wojnicz, Romuald; Nowalany-Kozielska, Ewa; Wojciechowska, Celina; Glanowska, G; Wilczewski, Przemysław; Niklewski, Tomasz; Zembala, Marian; Poloński, Lech; Rozek, Marius M.; Wodniecki, J

doi:10.1161/01.cir.104.1.39

Cited by 414 publications

(321 citation statements)

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“…Kühl et al (9) also demonstrated that immunosuppressive treatment in a subgroup of patients with dilated cardiomyopathy having continuing active inflammatory process results in a clinical, hemodynamic, and immunohistological improvement in 60%-70% of patients. Moreover, Wojnicz et al (10) showed a long-term benefit of immunosuppression with prednisone and azathioprine in patients with dilated cardiomyopathy because of immunohistologically proven myocarditis. However, we had no proven data regarding the status of inflammatory process in the myocardium of our patients with AS.…”

Section: Discussionmentioning

confidence: 99%

Left ventricular systolic dysfunction in two patients with ankylosing spondylitis: What is the role of corticosteroids?

2017

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IntroductionAnkylosing spondylitis (AS) is a chronic inflammatory condition that most commonly affects the axial skeleton, including the spine and sacroiliac joints. The most common cardiac manifestation in patients with AS is the aortic root and valve disease, which has been reported in up to 82% of patients (1). Other less common cardiac abnormalities that are observed in patients with AS include conduction and rhythm abnormalities, decreased coronary flow reserve, myocardial infarction, and diastolic dysfunction. However, the presence of systolic dysfunction has been less described in patients with AS. Herein we present two cases of idiopathic dilated cardiomyopathy in patients with AS. These patients were noted to have an improvement of their ejection fractions following treatment of AS, suggesting that cardiomyopathy in AS may be reversible with an effective treatment of the underlying inflammatory process. Written informed consent was obtained from patients who participated in this study. Case PresentationsCase 1 A 25-year-old man, with a known case of AS since 18 months, was referred to our Heart Failure Clinic with the New York Heart Association (NYHA) function class II of dyspnea on exertion. Heart failure was diagnosed prior to his rheumatologic problem, and he was partially treated using an angiotensin-converting enzyme inhibitor [captopril (Captopril, Rouz Darou; Tehran, Iran) 25 mg/BID (i.e., two times a day)] only. Complete rheumatologic panels were ordered, which established the presence of a seronegative spondyloarthropathy. He was receiving indomethacin (Indomethacin, Loghman; Tehran, Iran), sulfasalazine (Sulfasalazine, Mehr Darou; Tehran, Iran), and prednisolone (Prednisolone, Iran Hormone; Tehran, Iran) for AS. Sulfasalazine and prednisolone were initiated after an AS diagnosis, and the doses were maintained at 2000 and 2.5 mg daily, respectively.On arrival to our clinic, his cardiovascular examination revealed a regular heart rate, normal S1 and S2, and left-sided S3. No jugular venous distension was noted. The baseline echocardiography revealed mild left ventricular (LV) enlargement with severe systolic dysfunction [left ventricular ejection fraction (LVEF)=30%] and grade 2 diastolic dysfunction, normal right ventricular (RV) size and function, estimated systolic pulmonary artery pressure of 30 mmHg, no aortic stenosis or regurgitation, mild mitral regurgitation, and mild tricuspid regurgitation. Tissue Doppler study confirmed a reduced systolic myocardial velocity and a significant diastolic dysfunction. A complete laboratory examination, including electrocardiogram, calcium and magnesium levels, complete blood test, liver function tests, renal function tests (blood urea nitrogen and creatinine levels), serum electrolyte levels, thyroid-stimulating hormone levels, hemoglobin A1C, lipid profile, human immunodeficiency virus serological screening, and antinuclear antibody titer, 179Ankylosing spondylitis (AS) is a chronic inflammatory condition that most commonly affects the axial ...

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Section: Discussionmentioning

confidence: 99%

Left ventricular systolic dysfunction in two patients with ankylosing spondylitis: What is the role of corticosteroids?

2017

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“…The first and third patients, in accordance with the EMB results, were treated with immunosuppressive combination therapy. In addition to the studies published by Midei 18 and Melvin 19 of PPCM patients, the effectiveness of such therapy was demonstrated in patients with "nonpregnancy-associated myocarditis" in two randomized trials by Wojnicz 20 and Frustaci 21 . In both of our patients treated with immunosuppressive therapy, the number of infiltrating inflammatory cells significantly decreased, but the effect on the improvement of LV function was not entirely convincing.…”

Section: Discussionmentioning

confidence: 99%

“…Its effect has been studied with promising results in animal models and also in a pilot proof-of-concept study of 20 women 23 . The use of immunosuppressive therapy is offered as a parallel to studies with inflammatory cardiomyopathy in patients with biopsy-proven myocarditis, where a viral (or other) genome is not present in the myocardium 20,21 . There are only limited data from patients with PPCM.…”

Section: Discussionmentioning

confidence: 99%

The variable clinical course of peripartum cardiomyopathy

Krejčí¹,

Hude²,

Špinarová³

et al. 2014

BIOMED PAP

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“…The causes of DCM are multifactorial, but a viral or immune mechanism is suspected in some cases (2) because examination of heart tissues obtained during surgery has revealed inflammatory lesions in many patients with DCM (3). On the basis of these findings, several immunosuppressive therapies, including steroid and azathioprine administration (4,5), immunoadsorption (6), and Ig therapy (2), have been attempted. Although the general outcome of these treatments was disappointing, immunoadsorption therapy increased the survival rate for a subset of patients by 5 years after treatment (7).…”

Section: Ilated Cardiomyopathy (Dcm)mentioning

confidence: 99%

Matrix Metalloproteinase (MMP)-9, but Not MMP-2, Is Involved in the Development and Progression of C Protein-Induced Myocarditis and Subsequent Dilated Cardiomyopathy

Matsumoto

Park

Kohyama

2009

The Journal of Immunology

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Repeated or continuous inflammation of the heart is one of the initiation factors for dilated cardiomyopathy (DCM). In previous studies, we established a DCM animal model by immunizing rats with cardiac C protein. In the present study, we analyze the role of matrix metalloproteinases (MMPs) in experimental autoimmune carditis (EAC) and subsequent DCM to elucidate the pathomechanisms of this disease. In this model, inflammation begins ∼9 days after immunization. At that time, MMP activities were detected by in situ zymography. Real-time PCR analysis revealed continuous up-regulation of MMP-2 mRNA from 2 wk and thereafter. MMP-9 mRNA, however, had only a transient increase at 2 wk. Double staining with in situ zymography and cell markers demonstrated that gelatinase (MMP-2 and MMP-9)-expressing cells are infiltrating macrophages during the early stage and cardiomyocytes at later stages. Minocycline, which inhibits MMP-9 activities more strongly than MMP-2, significantly suppressed EAC, but an MMP-2-specific inhibitor, TISAM, did not affect the course of the disease. Furthermore, immunohistochemical examination revealed that minocycline treatment suppressed T cell and macrophage infiltration strongly, whereas TISAM did not. These findings indicate that MMP-9, but not MMP-2, is involved in the pathogenesis of the acute phase of EAC, and further suggest that MMP-9 inhibitors, minocycline and its derivatives, may be useful therapies for EAC and DCM.

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Randomized, Placebo-Controlled Study for Immunosuppressive Treatment of Inflammatory Dilated Cardiomyopathy

Abstract: These data demonstrate a long-term benefit of immunosuppressive therapy in patients with dilated cardiomyopathy and HLA upregulation on biopsy specimens. Thus, restoration of immunosuppressive therapy for such patients should be considered.

Cited by 414 publications

References 27 publications

Left ventricular systolic dysfunction in two patients with ankylosing spondylitis: What is the role of corticosteroids?

Left ventricular systolic dysfunction in two patients with ankylosing spondylitis: What is the role of corticosteroids?

The variable clinical course of peripartum cardiomyopathy

Matrix Metalloproteinase (MMP)-9, but Not MMP-2, Is Involved in the Development and Progression of C Protein-Induced Myocarditis and Subsequent Dilated Cardiomyopathy

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