Asymptomatic myocardial dysfunction was revealed by feature tracking cardiac magnetic resonance imaging in patients with primary Sjögren's syndrome.

AIM: To evaluate subclinical left ventricular (LV) regional dysfunction in patients with primary Sjögren's syndrome (pSS) using feature tracking cardiac magnetic resonance (FT-CMR) imaging and to identify pSS characteristics independently associated with LV regional dysfunction. METHOD: Fifty patients with pSS and 20 controls without cardiovascular disease underwent non-contrast CMR imaging. Labial gland biopsy was performed in 42 patients (84%). Disease activity was assessed using the European League Against Rheumatism Sjögren's syndrome disease activity index (ESSDAI). LV global longitudinal strain (GLS), global circumferential strain (GCS), and global radial strain (GRS) were measured using FT-CMR. RESULTS: No significant differences in cardiovascular risk factors were found between the pSS group and controls. The pSS group had significantly lower GLS (P = .015) and GCS (P = .008) than the control group. Multiple linear regression analysis indicated that GCS was significantly associated with Raynaud's phenomenon (P = .015), focus score ≥2 (P = .032), and total ESSDAI score ≥8 (P = .029). CONCLUSION: FT-CMR can reveal subclinical LV regional dysfunction in patients with pSS without cardiovascular disease. Furthermore, patients with pSS and Raynaud's phenomenon, a focus score ≥2, or an ESSDAI score ≥8 were considered to be at high risk for myocardial dysfunction.

Salivary Gland Focus Score Is Associated With Myocardial Fibrosis in Primary Sjögren Syndrome Assessed by a Cardiac Magnetic Resonance Approach.

OBJECTIVE: The risk of clinically manifested major cardiovascular (CV) events in primary Sjögren syndrome (pSS) remains unclear. This study aimed to assess myocardial fibrosis in pSS and investigate the associated disease characteristics by cardiac magnetic resonance imaging (cMRI). METHODS: We performed a cross-sectional study of patients with pSS without cardiac symptoms. Labial gland biopsy was documented in 44 patients (85%). Patients without CV risk factors underwent contrast-enhanced cMRI. Late gadolinium enhancement (LGE) was used to assess myocardial fibrosis. Myocardial edema was assessed using T2-weighted imaging (T2WI). We compared the left ventricular (LV) geometry and function between the groups with and without LGE. Further, we explored the associations of cMRI abnormalities with pSS characteristics. RESULTS: Fifty-two women with pSS (median age 55, IQR 47.0-65.7 yrs) were enrolled in the study. LGE was observed in 10 patients (19%), two of whom showed high intensity on T2WI. High intensity on T2WI was observed in 3 patients (5.8%). LV mass index and LV mass/end-diastolic volume tended to be higher in the LGE-positive group than in the LGE-negative group (P = 0.078 and 0.093, respectively). Salivary gland focus score (FS) ≥ 3 was independently associated with LGE-positive in the multivariable analysis (OR 11.21, 95% CI 1.18-106.80). CONCLUSION: Subclinical myocardial fibrosis, as detected by cMRI, was frequent in patients with pSS without cardiac symptoms. Abnormal cMRI findings were associated with salivary gland FS ≥ 3.

Impact of biological treatment on left ventricular dysfunction determined by global circumferential, longitudinal and radial strain values using cardiac magnetic resonance imaging in patients with rheumatoid arthritis.

AIM: To evaluate left ventricular (LV) dysfunction in patients with rheumatoid arthritis (RA) and to determine the impact of biological treatment on LV function in these patients using global circumferential strain (GCS), global longitudinal strain (GLS) and global radial strain (GRS) values assessed by feature tracking cardiac magnetic resonance (FT-CMR) imaging. METHODS: Eighty patients with RA and 20 controls without cardiovascular disease underwent non-contrast CMR imaging. Patients with RA received conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) or biologic DMARDs (bDMARDs). Global strains were calculated in 16 LV segments. RESULTS: No significant differences in cardiovascular risk factors were found between the RA group and controls. GCS was 21% lower in the RA group compared with controls (P < 0.001) and was 14% lower in the csDMARDs group compared with the bDMARDs group (P = 0.002), whereas, there was no significant difference in GLS and GRS between the RA group and the controls. In regard to strain rates, diastolic GCS and GRS rates were significantly lower in the RA group (P < 0.001, 0.011, respectively). In univariate analyses, GCS was significantly associated with the Simplified Disease Activity Index, bDMARDs, swollen joint count, anti-cyclic citrullinated peptides antibodies and matrix metalloproteinase-3, but in multivariable analysis, only bDMARDs was significantly associated with GCS (P = 0.021). CONCLUSION: Global circumferential strain, GLS and GRS assessed by FT-CMR can reveal subclinical LV dysfunction in patients with RA. Furthermore, they can be used to determine the normalization of LV regional dysfunction induced by bDMARDs possibly related to disease activity reduction.

Association of cardiac magnetic resonance-detected myocardial abnormalities with disease characteristics and brain natriuretic peptide levels in systemic sclerosis without cardiac symptoms.

AIM: This study aimed to evaluate the association between myocardial abnormalities and left ventricular (LV) geometry as assessed using cardiac magnetic resonance imaging (CMRI) in systemic sclerosis (SSc) patients without cardiac symptoms. METHODS: SSc patients without cardiac symptoms or cardiovascular risk factors underwent contrast CMRI. CMRI were assessed for structural and functional LV parameters and myocardial fibrosis based on myocardial late gadolinium enhancement (LGE). The correlation between brain natriuretic peptide (BNP) levels and LGE status was evaluated. RESULTS: Among 49 patients, 27 (55%) showed LGE positivity. The most common identified LGE pattern was a linear pattern. LGE was not consistent with coronary artery distribution. There was no difference in ejection fraction between those with and without LGE. LV morphological changes were observed in 29% of SSc patients. An abnormal LV structure was detected in 44% and 14% of patients in the LGE+ and LGE- groups, respectively. The BNP levels were higher by 57% in the LGE+ group than in the LGE-group. Receiver operating characteristic analysis showed that BNP levels reliably detected myocardial abnormalities (area under the curve, 0.72; 95% confidence interval 0.58-0.88). CONCLUSIONS: Myocardial abnormalities were common in SSc patients without cardiac symptoms. We suggest that LV morphological changes may have resulted from myocardial abnormalities. BNP may be useful as a screening tool for the detection of myocardial abnormalities in SSc patients.

Heart Rate-corrected QT Interval Duration in Rheumatoid Arthritis and Its Reduction with Treatment with the Interleukin 6 Inhibitor Tocilizumab.

OBJECTIVE: Individuals with rheumatoid arthritis (RA) are at a heightened risk of sudden cardiac death, an outcome increased in those with prolongation of the corrected electrocardiographic QT interval (QTc). We compared QTc between patients with RA and demographically matched controls and studied the change in QTc after treatment with the interleukin 6 inhibitor tocilizumab (TCZ). METHODS: Standard 12-lead electrocardiograms were obtained and QTc was measured in patients with RA at baseline and after 24 weeks of TCZ treatment, then compared with non-RA controls who were frequency-matched on age and sex. Indicators of the baseline QTc and predictors of change in QTc were studied using multivariable linear regression. RESULTS: A total of 94 RA and 42 non-RA controls were studied. The average baseline QTc was 10 ms longer in the RA group vs controls (422 vs 412 ms, respectively; p < 0.001) and decreased to an average of 406 ms with treatment (p < 0.001). Baseline QTc was significantly and independently higher among those with anticyclic citrullinated peptide antibodies seropositivity, higher swollen joint counts, and higher levels of C-reactive protein (CRP) and matrix metalloproteinase 3. Each log unit decrease in CRP with treatment was associated with an average reduction in QTc of 2.9 ms (p = 0.002) after adjusting for age and baseline QTc. Clinical response measures were not associated with the change in QTc. CONCLUSION: The marked normalization of QTc observed with TCZ treatment, and its close parallel with CRP reduction, support the premise that systemic inflammation contributes to cardiac repolarization abnormalities in RA that may be amenable to treatment.

Magnetic Resonance Imaging-Detected Myocardial Inflammation and Fibrosis in Rheumatoid Arthritis: Associations With Disease Characteristics and N-Terminal Pro-Brain Natriuretic Peptide Levels.

OBJECTIVE: Myocardial dysfunction and heart failure (HF) are increased in rheumatoid arthritis (RA), yet there are few studies of the myocardium in RA. METHODS: RA patients with no known heart disease or risk factors underwent gadolinium-enhanced cardiac magnetic resonance imaging (MRI). Images were assessed for left-ventricular (LV) structural and functional parameters and for myocardial late gadolinium enhancement (LGE; an indicator of myocardial fibrosis) and T2-weighted imaging (an indicator of active inflammation). We modeled the associations between RA characteristics and N-terminal pro-brain natriuretic protein (NT-proBNP) levels with LGE and T2-weighted imaging. We also assessed whether LGE and/or T2-weighted imaging were associated with abnormal LV structure or dysfunction. RESULTS: A total of 60 RA patients were studied. LGE was present in 19 (32%) and T2-weighted imaging in 7 (12%), 5 of whom also had LGE. After adjustment for relevant confounders, higher odds of LGE with each swollen joint (odds ratio [OR] 1.87, P = 0.008), each log unit higher C-reactive protein level (OR 3.36, P = 0.047), and each log unit higher NT-proBNP (OR 20.61, P = 0.009) were found. NT-proBNP was also significantly higher (135%) among those with T2-weighted imaging than in those without T2-weighted imaging or LGE. Higher LV mass index and LV mass:end diastolic volume ratio were observed in those with T2-weighted imaging than in those with no myocardial abnormalities and in those with LGE without T2-weighted imaging; however, ejection fraction was not reduced in those with either LGE or T2-weighted imaging. CONCLUSION: These data suggest that cardiac MRI findings indicating myocardial inflammation/fibrosis are correlated with RA disease activity and alterations in myocardial structure known to precede clinical HF.

Detection of Left Ventricular Regional Dysfunction and Myocardial Abnormalities Using Complementary Cardiac Magnetic Resonance Imaging in Patients with Systemic Sclerosis without Cardiac Symptoms: A Pilot Study.

Objective We sought to detect the presence of left ventricular regional dysfunction and myocardial abnormalities in systemic sclerosis (SSc) patients without cardiac symptoms using a complementary cardiac magnetic resonance (CMR) imaging approach. Methods Consecutive patients with SSc without cardiac symptoms and healthy controls underwent CMR on a 1.5 T scanner. The peak systolic regional function in the circumferential and radial strain (Ecc, % and Err, %) were calculated using a feature tracking analysis on the mid-left ventricular slices obtained with cine MRI. In addition, we investigated the myocardial characteristics by contrast MRI. Pharmacological stress and rest perfusion scans were performed to assess perfusion defect (PD) due to micro- or macrovascular impairment, and late gadolinium enhancement (LGE) images were obtained for the assessment of myocarditis and/or fibrosis. Results We compared 15 SSc patients with 10 healthy controls. No statistically significant differences were observed in the baseline characteristics between the patients and healthy controls. The mean peak Err and Ecc of all segments was significantly lower in the patients than the controls (p=0.011 and p=0.003, respectively). Four patients with LGE (28.6%) and seven patients with PD (50.0%) were observed. PD was significantly associated with digital ulcers (p=0.005). Utilizing a linear regression model, the presence of myocardial LGE was significantly associated with the peak Ecc (p=0.024). After adjusting for age, the association between myocardial LGE and the peak Ecc was strengthened. Conclusion A subclinical myocardial involvement, as detected by CMR, was prevalent in the SSc patients without cardiac symptoms. Regional dysfunction might predict the myocardial abnormalities observed in SSc patients without cardiac symptoms.

[A case of probable catastrophic antiphospholipid syndrome with multi-organ failure presenting as a transient increase of antiphospholipid antibody levels].

A 44-year-old woman was admitted to our hospital with shock, massive pneumonia and respiratory failure, liver and renal dysfunction, and cerebral infarction. Based on these symptoms, we suspected the presence of disseminated intravascular coagulation and multiple organ dysfunctions due to massive pneumonia or catastrophic antiphospholipid syndrome (CAPS). Therefore, the patient was placed on a respirator and was administered ciprofloxacin, doripenem hydrate, thrombomodulin, antithrombin III, and methylprednisolone pulse therapy. Because the patient's antiphospholipid antibody titer was low on the day of admission (day 1), we did not include CAPS in the differential diagnosis and discontinued prednisolone treatment on day 6. However, the anticardiolipin immunoglobulin M antibody titer was found to be elevated on day 7; in addition, a transient increase in the anticardiolipin anti-ß2 glycoprotein antibody titer was noted on re-examination. Moreover, on day 8, the thrombopenia and alveolar hemorrhage suddenly exacerbated. We finally diagnosed the patient with CAPS, and therefore resumed methylprednisolone therapy. Subsequently, the inflammation, respiratory failure, and thrombopenia rapidly improved, and the patient was extubated on day 12.

A case of adult-onset Still's disease complicated by thrombotic thrombocytopenic purpura with retinal microangiopathy and rapidly fatal cerebral edema.

We present a patient who had adult-onset Still's disease (AOSD) complicated by thrombotic thrombocytopenic purpura (TTP) that resulted in retinal microangiopathy and rapidly fatal cerebral edema. The patient was a 37-year-old male who developed fever, eruption, arthritis and hepatic dysfunction, that, based on close examination, was diagnosed as AOSD. Despite treatment with corticosteroids, the patient developed acute visual field defect, neurological deterioration including convulsions and impaired consciousness, as well as acute renal failure that ultimately resulted in death. Pathological examination of autopsy specimens revealed multiple fibrin thrombi disseminated in small vessels of the brain and kidney, which was consistent with TTP, along with marked cerebral edema. Although TTP has rarely been reported in association with AOSD, awareness of the possible coexistence of these two diseases is important for diagnosis and treatment.

A case of adult onset Still's disease complicated with cryptogenic organizing pneumonia.

Only a few pathologic reports exist describing adult onset Still's disease (AOSD) with pulmonary involvement. We report this very rare case of AOSD complicated with cryptogenic organizing pneumonia (COP). A 32-year-old woman was referred with high spiking fever, salmon-pink rash in her arms and legs, and polyarthralgia. The laboratory data showed marked increases in white blood cell count, an erythrocyte sedimentation rate, and C reactive protein, ferritin, and liver dysfunction. All cultures remained negative, as were autoantibodies and rheumatoid factor. The patient was strongly suspected of AOSD according to specific diagnostic criteria. However, chest X ray disclosed an infiltrative shadow accompanied by air bronchogram in the upper lobe of the right lung and therapy with antibiotics was initiated. As the patient did not respond to antibiotics and a remittent fever of over 38°C, a flexible bronchoscopy was performed. Organizing pneumonia was diagnosed by transbronchial lung biopsy (TBLB) histology and radiologically, and the lesions were thought to be due to pulmonary involvement of AOSD. Therefore, she was diagnosed with AOSD complicated with COP. Oral treatment with prednisolone (30 mg/day) resulted in rapid disappearance of the infiltrative shadow. Symptoms and markers of inflammation also improved. Clinicians should be aware that COP can be a complication of AOSD.

Efficacy and safety of single-dose mizoribine for patients with rheumatoid arthritis: results at 6 months after switching from a multiple-dose regimen without a change in total daily dose.

To determine the efficacy and safety of single-dose mizoribine (MZR) for patients with rheumatoid arthritis (RA), a 6-month, single-arm, open-label, prospective observation study was performed. In patients who had been taking MZR at 100-150 mg/day in 2-3 divided portions continuously for at least 3 months, and who had shown a lack of clinical response, or escape (defined as a lack of response at the time of switching, even if some form of response had been shown before that), multiple-dose administration was switched to single-dose administration without changing the total daily dose. Efficacy was assessed in terms of the disease activity score, using the 28-joint count and erythrocyte sedimentation rate (DAS 28-ESR). Of the 34 enrolled patients, 28 met all the eligibility criteria and were assessed for efficacy, and finally 26 patients were able to receive the single-dose regimen throughout the full 6 months. The DAS28-ESR showed a significant decrease from 2 months after switching, and 46.4% of the 28 patients finally achieved a good or moderate response (3 and 10 patients, respectively). With regard to safety, no serious adverse events were observed. In conclusion, the administration of MZR at 100 or 150 mg in a single dose is thought to be a useful alternative form of MZR therapy.

Assessment of myocardial abnormalities in rheumatoid arthritis using a comprehensive cardiac magnetic resonance approach: a pilot study.

INTRODUCTION: Rheumatoid arthritis (RA) is a multi-organ inflammatory disorder associated with high cardiovascular morbidity and mortality. We sought to assess cardiac involvement using a comprehensive cardiac magnetic resonance imaging (cMRI) approach and to determine its association with disease characteristics in RA patients without symptomatic cardiac disease. METHODS: RA patients with no history and/or clinical findings of systemic or pulmonary hypertension, coronary artery disease, severe valvular heart disease, atrial fibrillation, diabetes mellitus, or echocardiographic abnormalities underwent contrast-enhanced cMRI on a 1.5T scanner. Adenosine triphosphate was used to assess perfusion defects due to microvascular impairment or ischemia, and delayed enhanced imaging was obtained for the assessment of myocardial inflammation/fibrosis. We explored the associations of cMRI abnormalities with RA disease activity and severity measures. RESULTS: Eighteen patients (78% female) with a mean age of 57 ± 10 years were studied. Eight patients (45%) demonstrated a myocardial abnormality. Perfusion defects under pharmacologic stress were seen in two patients (11%), one of whom had a circumferential subendocardial perfusion defect and one had a non-segmental subendocardial perfusion defect. Seven patients (39%) were found to have delayed enhancement, only one of whom also demonstrated a perfusion defect. Mean disease activity score (DAS)28 was significantly higher in the group with delayed enhancement compared to the group without by an average of 1.32 DAS28 units (4.77 vs. 3.44 units, respectively; P = 0.011). Corresponding trends to statistical significance were noted in systemic inflammatory markers, with both C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) quantitatively higher in the group with delayed enhancement. Other RA characteristics, such as disease duration, autoantibody status, and current treatments were not significantly associated with cardiac involvement. CONCLUSIONS: Myocardial abnormalities, as detected by cMRI, were frequent in RA patients without known cardiac disease. Abnormal cMRI findings were associated with higher RA disease activity, suggesting a role for inflammation in the pathogenesis of myocardial involvement in RA.

Behçet's disease initially presenting with meningitis and sudden hearing loss.

We report a patient with neuro Behçet's disease (BD) initially presenting with meningitis and severe hearing loss. A 51-year-old man with no noteworthy past history was hospitalized for evaluation of non-pulsating headache and high fever. Lumbar puncture on admission only showed slight pleocytosis (6 /microL, monomorphonuclear cells predominantly) but no evidence of meningitis. However, after admission, he continued to have a fever of over 38 degrees, and he developed painful oral aphthous ulcer and pseudofolliculitis on the upper limbs and trunk. Prior to admission he had often experienced oral ulceration and had bought commercially available mouthwash for prophylaxis. Subsequently, genital ulceration appeared. A small ulcer was observed at the blood collection site, leading to the diagnosis of BD. On the seventh hospital day, the patient developed sudden hearing loss, which was diagnosed as severe sensorineural hearing loss. Lumbar puncture was performed again. Cerebrospinal fluid (CSF) analysis showed mild pleocytosis (60 /microL, predominantly monomorphonuclear cells), with high CSF IL-6 levels. Neither edematous change nor atrophy of the brainstem was noted and there were no other abnormal findings on the brain MRI/MRA. Auditory brainstem response was normal, suggesting that the patient had developed hearing loss due to peripheral neuropathy. We speculate that the hearing loss was likely due to vasculitis associated with BD. This case is considered to be a rare case of Behçet's disease caused by severe hearing loss and meningitis.