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Original Research: Diffuse Lung Disease |

Incidence and Prognostic Significance of Myocardial Late Gadolinium Enhancement in Patients With Sarcoidosis Without Cardiac ManifestationEnhanced MRI in Extracardiac Sarcoidosis FREE TO VIEW

Toshiyuki Nagai, MD, PhD; Shun Kohsaka, MD, PhD; Shigeo Okuda, MD, PhD; Toshihisa Anzai, MD, PhD; Koichiro Asano, MD, PhD; Keiichi Fukuda, MD, PhD
Author and Funding Information

From the Department of Cardiovascular Medicine (Drs Nagai and Anzai), National Cerebral and Cardiovascular Center, Osaka; Department of Cardiology (Drs Kohsaka and Fukuda), Keio University School of Medicine, Tokyo; Department of Diagnostic Radiology (Dr Okuda), Keio University School of Medicine, Tokyo; and the Division of Pulmonary Medicine (Dr Asano), Department of Medicine, Tokai University School of Medicine, Kanagawa, Japan.

CORRESPONDENCE TO: Toshiyuki Nagai, MD, PhD, Department of Cardiovascular Medicine, National Cerebral and Cardiovascular Center, 5-7-1 Fujishirodai, Suita, Osaka 565-8565, Japan; e-mail: nagai@ncvc.go.jp


Drs Nagai and Kohsaka contributed equally to this work.

FUNDING/SUPPORT: This work was supported by a Grant-in-Aid for Young Scientists [Grant 25860630 to Dr Nagai] from the Japan Society for the Promotion of Science.

Reproduction of this article is prohibited without written permission from the American College of Chest Physicians. See online for more details.


Chest. 2014;146(4):1064-1072. doi:10.1378/chest.14-0139
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BACKGROUND:  Cardiac death is the leading cause of mortality associated with sarcoidosis in Japan. However, the involvement of sarcoidosis infiltration often remains undetected. Recently, late gadolinium enhancement with cardiovascular MRI (LGE-CMR) imaging has been introduced for the detection of myocardial infiltrative disease, as it enables the detection of even minor myocardial damage. We investigated the incidence and prognostic value of LGE-CMR in patients with extracardiac sarcoidosis without cardiac manifestations.

METHODS:  Sixty-one consecutive patients who met the histologic and clinical criteria for sarcoidosis, and who did not have signs or symptoms of cardiovascular involvement, were prospectively recruited. LGE-CMR was performed at the time of enrollment, and patients were classified into positive or negative late gadolinium enhancement groups based on the findings. The study end point was a composite of all-cause death, symptomatic arrhythmia, and heart failure necessitating admission.

RESULTS:  Patients were predominantly middle aged (57 ± 15 years) and female (66%), and most had stable disease activity that did not require treatment with immunosuppressants. LGE-CMR detected cardiac involvement in eight patients (13%). Interventricular septal thinning detected by echocardiography was an independent predictor of LGE-CMR-detected cardiac involvement. During the follow-up period of 50 ± 12 months, no significant difference in adverse events was noted between patients in the LGE-CMR-positive and LGE-CMR-negative groups.

CONCLUSIONS:  LGE-CMR detected cardiac involvement in 13% of patients with sarcoidosis without cardiac manifestation, but both patients with and without LGE had relatively low event rates.

TRIAL REGISTRY:  Japan Primary Registries Network; No.: UMIN000001549; URL: www.umin.ac.jp

Figures in this Article

Sarcoidosis is a multiorgan disorder of unknown etiology that is characterized by granulomatous formation.1 Although the disease is thought to have low mortality and a benign prognosis, cardiac involvement may worsen the prognosis, as it leads to left ventricular dysfunction, congestive heart failure,2 and life-threatening cardiac arrhythmias.3 The mortality in patients with sarcoidosis with cardiac manifestation is as high as 25% in Western countries4 and is even higher in the Japanese population,5 indicating the need for therapeutic intervention.

Cardiac sarcoidosis is characterized by the presence of cardiac symptoms, particularly impaired systolic left ventricular function, or ECG changes. Frequently, however, the only indicators of cardiac sarcoidosis are minor ECG abnormalities and atypical cardiac symptoms, such as bundle branch and atrioventricular block, and ventricular arrhythmia. Furthermore, cardiac involvement in sarcoidosis is difficult to detect because the infiltration of granulomas into cardiac tissue is often not associated with clinical symptoms.6,7 Thus, early detection of cardiac involvement in patients with sarcoidosis may improve treatment strategies and mortality.

Noninvasive imaging approaches, such as late gadolinium enhancement (LGE) with cardiovascular MRI (CMR) (LGE-CMR), have enabled detection of cardiac infiltration of sarcoidosis at much earlier phases of the disease.8,9 LGE distribution varies according to the type of myocardial disease. For example, gadolinium is predominantly distributed in the endocardium of patients with ischemic cardiomyopathy, in the myocardial wall of patients with dilated cardiomyopathy, and in the epicardium of patients with myocarditis.10,11 Several studies have demonstrated that CMR is able to detect characteristic fibrosis patterns of cardiac sarcoidosis, such as septal thinning, ventricular dilation, and systolic dysfunction.12,13 LGE-CMR is reported to have high sensitivity and specificity for the detection of cardiac involvement in patients with sarcoidosis, who typically exhibit a nonischemic pattern of LGE.14,15

Patel et al9 reported a retrospective analysis of patients with systemic sarcoidosis. In their study, 19% of patients with systemic sarcoidosis with preserved ejection fraction (left ventricular ejection fraction [LVEF] > 50%) showed LGE; some of these patients had cardiac symptoms or an ECG abnormality (37%), and one-quarter (25%) satisfied the Japanese Ministry of Health and Welfare (JMHW) criteria. This study was limited to investigating the characteristics of the LGE-positive and LGE-negative groups and did not include outcome. Patel et al8 also demonstrated that the prevalence of myocardial damage detected by LGE-CMR in patients with extracardiac sarcoidosis was 26%, and the presence of LGE predicted future adverse events. Their prospective cohort specifically included patients with left ventricular dysfunction, cardiac manifestation (21%), and those who already satisfied the JMHW criteria (10%). Notably, their LGE-positive group had significantly lower LVEF compared with the LGE-negative group; thus, the results were easily understandable.

Therefore, based on these studies, the role of LGE-CMR in less symptomatic patients is still unclear. Detection of myocardial damage by LGE-CMR in patients with extracardiac sarcoidosis without cardiac manifestation is becoming common in daily practice, and the aim of the current study is to clarify the usefulness of LGE-CMR for detecting myocardial damage and future risk stratification in such patients with sarcoidosis.

Patient Population

A total of 61 consecutive patients who were histologically and/or clinically diagnosed with extracardiac sarcoidosis, including lung, eye, and skin involvement, were prospectively assessed. Inclusion criteria were the absence of cardiac symptoms suggestive of ischemic or other heart disease; LVEF ≥ 50%; no contraindication for LGE-CMR, such as renal impairment or implanted metallic device; and not meeting the diagnostic criteria for cardiac sarcoidosis by tests other than LGE-CMR, as described in the 2006 revised version of the JMHW guidelines.16,17

Patients were divided into LGE-CMR-positive and LGE-CMR-negative groups based on the results of CMR imaging performed during an initial evaluation. All subjects provided written informed consent prior to participation in the study. The study was approved by the ethics committee of Keio University Hospital (20-77) and registered under the Japanese UMIN Clinical Trials Registry (UMIN000001549).

Blood Sampling and Testing

Prior to CMR, venous blood samples were collected, and the serum C-reactive protein (CRP) level was then measured by latex photometric immunoassay (Mitsubishi Chemical, Inc). Serum creatinine level was measured enzymatically using the creatinase-sarcosine oxidase-peroxidase method. Angiotensin-converting enzyme (ACE) activity was measured by the Kasahara method.18

Echocardiography

Echocardiography was performed prior to CMR. Left ventricular wall-motion abnormality and thinning of the interventricular septum (IVS) were interpreted by two experienced clinicians without knowledge of the patients’ background.

CMR Protocol

CMR was performed using a standardized clinical protocol on a 1.5-T magnetic resonance system (Signa TwinSpeed; General Electric Co). All CMR images were ECG-gated and obtained during repeated breath holds. Cine images were acquired with a steady-state free precession (SSFP) pulse sequence with the following parameters: repetition time, 4.8 milliseconds; echo time, 1.2 milliseconds; flip angle, 55°; matrix, 256 × 128; field of view, 350 mm; section thickness, 10 mm; section interval, 10 mm; and sensitivity encoding factor, ECG-gated inversion-recovery true fast imaging with SSFP performed in the mid-diastolic phase using an inversion time of 300 milliseconds. After localization of the heart, nine to 12 contiguous short-axis sections encompassing the entire left ventricle and two-, three-, and four-chamber, long-axis projections were collected. Gadopentetate meglumine (0.15 mmol/kg; Magnevist; Schering AG) was administered at a rate of 3 to 4 mL/s using a power injector, and delayed-enhancement images were acquired 10 min after the injection of gadopentetate meglumine, using an inversion-recovery SSFP pulse sequence. Seven short axial sections were obtained at each time point. Inversion time was fixed at 300 milliseconds after the R wave.

Study End Point and Clinical Follow-up

The study end point was a composite of all-cause death, heart failure necessitating admission, and symptomatic arrhythmia, which was defined as ventricular arrhythmia with clinical symptoms and necessitating admission, or bradyarrhythmia leading to pacemaker implantation. Follow-up data, including the results of additional LGE-CMR imaging performed after 6 months with patient permission, were obtained from hospital records; by direct contact with patients or patients’ physicians at hospital or outpatient clinic; telephone interview of patients or, if deceased, of family members; and mail, by dedicated coordinators and investigators.

Statistical Analysis

Continuous data are expressed as mean ± SD. LGE-CMR-positive and LGE-CMR-negative groups were compared using an unpaired t test or nonparametric means test for continuous variables. Categorical variables were reported as frequencies with percentages and compared between the two groups using the χ2 test and Fisher exact test. Long-term outcome was estimated using Kaplan-Meier curves and the log-rank (Mantel-Cox) test to assess the significance of differences according to the presence or absence of LGE. Multiple logistic regression analysis, including determinants with a P value < .10 in univariate analysis, was used to assess the effects of various factors on positive LGE. All statistical analyses were performed using SPSS 13.0 for Windows (IBM). Statistical significance was defined as P < .05.

Baseline and Clinical Characteristics

Patients were predominantly middle aged (57 ± 15 years) and female (66%) and had a relatively prolonged course of stable sarcoidosis (median, 38 months). Most patients (89%) had pulmonary involvement and were not treated with immunosuppressants (Table 1).

Table Graphic Jump Location
TABLE 1 ]  Baseline Characteristics of Patients

Continuous variables are presented as mean ± SD and categorical variables are presented as No. (%), unless otherwise indicated. ACE = angiotensin-converting enzyme; CRP = C-reactive protein; LGE = late gadolinium enhancement; Q = quarter; VC = volume capacity.

Delayed Enhancement Imaging

Eight of the 61 patients (13%) had positive LGE findings, including perimyocardial involvement in two patients (Fig 1A), transmyocardial involvement in two patients (Fig 1B), and intramyocardial involvement in four patients (Figs 1C, 1D).

Figure Jump LinkFigure 1 –  Representative findings and enhancement patterns in the late gadolinium enhancement-positive group (n = 8) of patients with extracardiac sarcoidosis patients. A, Perimyocardial pattern (n = 2). B, Transmyocardial pattern (n = 2). C and D, Intramyocardial pattern (n = 4).Grahic Jump Location
Differences Between LGE-Positive and LGE-Negative Groups

Although no significant differences were detected between the LGE-positive and LGE-negative groups with respect to baseline characteristics, extracardiac organ involvement, disease duration, and steroid use, the LGE-positive group tended to have a higher incidence of baseline steroid therapy and more organ involvement than the LGE-negative group (Table 1). Echocardiographic analysis revealed that the prevalence of IVS thinning was significantly higher in the LGE-positive group (38% vs 4%, P < .05). No difference in the prevalence of left ventricular wall-motion abnormality or positive gallium-scintigram findings was seen between the two groups (Table 2).

Table Graphic Jump Location
TABLE 2 ]  Baseline Cardiac Characteristics of Patients

Continuous variables are presented as mean ± SD, categorical variables are presented as No. (%). AVB = atrioventricular block; BBB = bundle branch block; CMR = cardiovascular MRI; Ga = gallium; IVS = interventricular septum; LVEDV = left ventricular end-diastolic volume; LVEF = left ventricular ejection fraction.

Blood tests revealed that serum ACE activity was significantly lower in the LGE-positive group, but no significant difference was detected for other laboratory test results, including CRP and hemoglobin levels, or lung volume capacity (Table 1).

In both groups, no patient had any signs suggestive of coronary artery disease (CAD). This included ischemic ST-T change and/or abnormal Q-wave in the ECG or local left ventricular wall-motion abnormality corresponding to coronary territory in the echocardiogram.

Determinants of Positive LGE

Univariate logistic regression analysis identified multiple organ involvement and IVS thinning as possible independent factors for positive LGE (P = .09 and P = .01, respectively) (Table 3). These two variables were included in a multivariate logistic regression analysis model, which revealed that IVS thinning shown by echocardiography was an independent determinant of positive LGE (OR, 11.7; 95% CI, 1.49-92.0; P = .019) (Table 3).

Table Graphic Jump Location
TABLE 3 ]  Logistic Regression Analysis for Determinants of Positive LGE

See Table 1 and 2 legends for expansion of abbreviations.

Short-term (6-Month) Outcomes of Patients in LGE-Positive Group

The characteristics of patients in the LGE-positive group are summarized in Table 4 and Figure 2. During the initial 6-month follow-up period, one patient (No. 1) underwent pacemaker implantation almost 1 month after CMR for advanced atrioventricular block. However, other patients did not experience any major adverse cardiac events. Four patients refused induction of steroid therapy, but did not show progression of LGE on follow-up CMR performed 6 months after study enrollment. Patient No. 8 was treated with steroids upon patient’s request, and LGE was not detected 6 months after initiating treatment.

Table Graphic Jump Location
TABLE 4 ]  Characteristics of Patients Positive for LGE

See Table 1 and 2 legends for expansion of abbreviations.

Figure Jump LinkFigure 2 –  Steroid therapy at first CMR and change in LGE after 6 mo. LGE = late gadolinium enhancement; CMR = cardiovascular MRI.Grahic Jump Location
Long-term Patient Outcomes

During the follow-up period of 50 ± 12 months, two patients were lost. One in the LGE-positive group (No. 2) was lost at 46 months after enrollment; the other, in the LGE-negative group, was lost at 37 months after enrollment. No patient in either group experienced cardiac death. In addition, no significant differences in the study end points were detected between the two groups (Fig 3). Three patients in the LGE-CMR-negative group died of noncardiac causes (hepatic cell carcinoma, malignant lymphoma, and pulmonary sarcoidosis).

Figure Jump LinkFigure 3 –  Kaplan-Meier curves for long-term adverse events (all-cause death, symptomatic arrhythmias, and heart failure necessitating admission). See Figure 2 legend for expansion of abbreviation.Grahic Jump Location

In this prospective study of 61 Japanese patients with extracardiac sarcoidosis, 13% of patients who did not meet the diagnostic criteria for cardiac sarcoidosis based on conventional assessment by ECG, echocardiography, and gallium scintigram nevertheless showed cardiac involvement on LGE-CMR. We also found that thinning of the IVS was an independent determinant of myocardial damage detected by LGE. However, cardiac involvement was not associated with a higher risk for short- or long-term adverse outcomes in this patient population. Together, these findings suggest that LGE-CMR sensitively detects cardiac involvement associated with extracardiac sarcoidosis, even during the clinically silent stages of cardiac involvement, but has limited prognostic implication in the absence of clinical cardiac manifestations, such as heart failure or symptomatic arrhythmias. This study could answer a very relevant clinical issue faced in the management of cardiac sarcoidosis patients: what to do about incidentally discovered CMR abnormalities in the context of systemic sarcoidosis. There are a few articles published on this issue, but no study has prospectively scanned individuals in the absence of cardiac symptoms.

The JMHW has established guidelines for the diagnosis of cardiac sarcoidosis,16 which include invasive diagnostic tests, such as myocardial biopsy, and noninvasive methods, including nuclear-medicine testing by thallium and gallium scintigraphy. However, these criteria suffer from low sensitivity12,19 and often fail to detect early signs of cardiac involvement, particularly myocardial infiltration and tissue damage. Therefore, the application of LGE-CMR as a diagnostic imaging approach for cardiac involvement in patients with extracardiac sarcoidosis requires the accurate detection of characteristic myocardial damage. In the present study, the LGE-positive group of patients with extracardiac sarcoidosis showed various types of LGE imaging patterns, including peri-, trans-, and intramyocardial involvement. The observed patterns are comparable to those reported by Watanabe et al,11 who examined CMR images of patients with cardiac sarcoidosis who were enrolled in a multicenter study and found that LGE was most frequent in the subepicardial layer, where the appearance of LGE staining was band-shaped with distinct margins. In addition, transmural lesions were more common in patients with reduced LVEF (<35%). However, even among patients who showed characteristic LGE images of cardiac sarcoidosis, a number were additionally diagnosed with various types of cardiomyopathy, including dilated and hypertrophic cardiomyopathy, which suggests that the observed patterns may not have been specific for damage caused by sarcoidosis.

Our current studies suggest that patients with extracardiac sarcoidosis with no cardiac symptoms and preserved left ventricular systolic function have better clinical outcomes and fewer events than those with symptomatic and left ventricular systolic dysfunction. Our present findings differ from the results of two similar studies conducted in Western countries, with respect to the detection rates of cardiac involvement and long-term outcomes of patients with LGE-positive sarcoidosis, even though the longer observation periods (from 3 to 4 years) and end points were similar.8,9 For example, the frequency of patients who were LGE positive in the previous studies ranged from 19% to 26%, which is approximately twofold higher than the detection rate of 13% in the present study. In addition, the rate of cardiac events in patients in the LGE-positive group (12.5%) was markedly lower than that of approximately 29% in one study,8 suggesting that differences in disease duration, inclusion criteria, or incidence of immunosuppressant use may have influenced the long-term outcome in these patient populations. With respect to disease duration, this study cohort had been diagnosed with sarcoidosis for a median of approximately 3 years as compared with 7 and 8 years in the previous studies, which may explain why cardiac involvement was more prevalent in the previous studies compared with the present study. Our LGE-positive group also had markedly lower use of steroids (11% vs 41% to 65%), and other immunosuppressants (0% vs 9% to 28%), indicating that they had a relatively stable disease condition. Further, the previous studies did not exclude patients with cardiac symptoms, severe ECG abnormalities, reduced left ventricular systolic function, or patients satisfying the JMHW criteria, which may also have led to the higher detection rates of cardiac involvement and poorer long-term outcomes.

We also found that IVS thinning detected by echocardiography was an independent determinant of positive LGE findings. Although thinning of the IVS was reported to be a characteristic manifestation of cardiac involvement,20 IVS thinning was only observed in 38% of patients who were LGE positive. However, this rate of detection was considerably higher than that of 20% reported in a study of Japanese patients with cardiac sarcoidosis.21 Although our present findings suggest that IVS thinning may be a predictor of myocardial damage detected by LGE, future prospective studies with larger cohorts are needed to confirm this possibility.

The treatment of patients with LGE-positive, extracardiac sarcoidosis without cardiac manifestations and preserved systolic function presents a challenge in the clinical setting with respect to steroid treatment. In the present study, five patients in the LGE-positive group were recommended for immunosuppressant therapy to treat the myocardial damage detected by CMR; however, four of these patients declined immunosuppressant therapy because of concerns related to adverse effects. Similar to the patients treated with steroid medications, however, none of the patients who declined steroid therapy had detectable progression or improvement of cardiac damage by LGE-CMR after 6 months. Notably, in one patient who agreed to steroid induction after the initial CMR, the small amount of myocardial damage had disappeared after 6 months. Patel et al8 reported that the dense fibrosis or granulomatous inflammation within patchy fibrotic lesions observed in autopsy heart specimens matched the LGE-CMR imaging findings. In addition, our present findings are consistent with a report showing that steroid treatment reduced the size of enhanced areas in LGE-CMR.22 However, close, long-term observation of the clinical course and outcome of patients with extracardiac sarcoidosis with cardiac involvement detected by LGE and who are not treated with steroid therapy after initial CMR should also provide critical information regarding the effectiveness of steroid therapy. Therefore, the detection of minor myocardial damage by LGE-CMR in patients with extracardiac sarcoidosis might provide a basis for discussion about steroid treatment in patients who would not otherwise meet indications for immunosuppressant therapy for extracardiac organs.

Further studies are needed to determine how LGE-CMR could contribute to the selection of therapeutic strategies for improving the long-term prognosis of extracardiac sarcoidosis with cardiac involvement, as has been suggested for various types of nonischemic cardiomyopathy.23 Mehta et al24 reported that positive programmed electric stimulation (PES) of the ventricle might help to identify patients with asymptomatic cardiac sarcoidosis at risk for ventricular arrhythmia; patients with negative PES also appeared to have a benign clinical course for the first several years following diagnosis. Therefore, this type of risk stratification together with LGE-CMR might be useful in further prospective studies of asymptomatic cardiac sarcoidosis. However, PES would be an invasive strategy, and difficult to use routinely for asymptomatic patients in clinical practice.

Several limitations of this study warrant mention. First, the number of patients positive for LGE was relatively small. However, we believe that the sample is representative of patients with extracardiac sarcoidosis. Second, the estimation of IVS thinning was based on qualitative assessment performed by two technicians and, as such, may have suffered from inaccuracy. Therefore, the use of standard assessment methods will be necessary in future studies investigating IVS thinning. Third, because patients were not monitored by 24-h ECG, it is possible that several tachyarrythmias and bradyarrhythmias were missed. For this reason, one of the study end points regarding arrhythmic events was defined as symptomatic arrhythmia including ventricular tachyarrhythmia necessitating admission and bradycardia leading to pacemaker implantation. Fourth, 18F-fluorodeoxyglucose PET, in addition to LGE-CMR, for detecting inflammatory activity was not performed, and there may be several uncertainties on the precise pathophysiologic interpretation of myocardial hyperenhancement. Fifth, we did not completely exclude CAD as a cause of LGE by coronary angiography, because the American Heart Association guidelines state that neither CT angiography nor magnetic resonance angiography should be used to screen for CAD in patients who have no signs or symptoms suggestive of CAD,25 and no patients in the current cohort had such signs or symptoms. In addition, no patient in the LGE-positive group had typical subendomyocardial damage (CAD pattern), as reported in the Results section. Sixth, cardiac involvement may be present in the absence of any abnormality on standard cardiac testing, may manifest as an abnormal ECG alone, or may be recognized as an asymptomatic abnormality on echocardiogram, or even on LGE-CMR. Considering these facts and the findings of our study, it would be difficult to distinguish between an earlier and clinically silent phase of cardiac sarcoidosis with detection of myocardial damage by multimodalities including LGE-CMR. Finally, the sample size was small, thereby limiting the ability to generalize the findings and the statistical power for detecting differences in negative data. Regarding the follow-up period, although it was longer than that of previous studies, it might be still inadequate to conclude that asysmptomatic patients in the LGE-positive and LGE-negative groups had similar outcomes; namely, the chance of a type 2 error is a possibility. Therefore, further prospective studies with a larger asymptomatic population and longer follow-up are warranted.

In conclusion, the present findings suggest that LGE-CMR is useful for the detection of cardiac involvement in patients with extracardiac sarcoidosis and no cardiac symptoms, preserved LVEF, and not satisfying JMHW criteria. Even in patients without cardiac manifestation, cardiac damage was detected in approximately 15% of patients, although those with and without LGE had similar clinical outcomes.

Author contributions: T. N. and S. K. had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. T. N. served as principal author. T. N., S. K., S. O., T. A., K. A., and K. F. contributed to the study design and data analysis; T. N., S. K., S. O., T. A., and K. A. contributed to data interpretation; T. N. and S. K. drafted the original manuscript and revised it critically with respect to intellectual content; and T. N., S. K., S. O., T. A., K. A., and K. F. approved the final version of the submitted manuscript.

Financial/nonfinancial disclosures: The authors have reported to CHEST that no potential conflicts of interest exist with any companies/organizations whose products or services may be discussed in this article.

Role of sponsors: The sponsor had no role in the design of the study, the collection and analysis of the data, or the preparation of the manuscript.

Other contributions: We thank Mizue Sato, AS; Ikuko Ueda, PhD; Jun Makino, BS; Mariko Kondo, BS; and Yukiho Hirota, BS (Keio University) for contributions to data collection and monitoring.

ACE

angiotensin-converting enzyme

CAD

coronary artery disease

CMR

cardiovascular MRI

CRP

C-reactive protein

IVS

interventricular septum

JMHW

Japanese Ministry of Health and Welfare

LGE

late gadolinium enhancement

LGE-CMR

late gadolinium enhancement with cardiovascular MRI

LVEF

left ventricular ejection fraction

PES

programmed electric stimulation

SSFP

steady-state free precession

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Figures

Figure Jump LinkFigure 1 –  Representative findings and enhancement patterns in the late gadolinium enhancement-positive group (n = 8) of patients with extracardiac sarcoidosis patients. A, Perimyocardial pattern (n = 2). B, Transmyocardial pattern (n = 2). C and D, Intramyocardial pattern (n = 4).Grahic Jump Location
Figure Jump LinkFigure 2 –  Steroid therapy at first CMR and change in LGE after 6 mo. LGE = late gadolinium enhancement; CMR = cardiovascular MRI.Grahic Jump Location
Figure Jump LinkFigure 3 –  Kaplan-Meier curves for long-term adverse events (all-cause death, symptomatic arrhythmias, and heart failure necessitating admission). See Figure 2 legend for expansion of abbreviation.Grahic Jump Location

Tables

Table Graphic Jump Location
TABLE 1 ]  Baseline Characteristics of Patients

Continuous variables are presented as mean ± SD and categorical variables are presented as No. (%), unless otherwise indicated. ACE = angiotensin-converting enzyme; CRP = C-reactive protein; LGE = late gadolinium enhancement; Q = quarter; VC = volume capacity.

Table Graphic Jump Location
TABLE 2 ]  Baseline Cardiac Characteristics of Patients

Continuous variables are presented as mean ± SD, categorical variables are presented as No. (%). AVB = atrioventricular block; BBB = bundle branch block; CMR = cardiovascular MRI; Ga = gallium; IVS = interventricular septum; LVEDV = left ventricular end-diastolic volume; LVEF = left ventricular ejection fraction.

Table Graphic Jump Location
TABLE 3 ]  Logistic Regression Analysis for Determinants of Positive LGE

See Table 1 and 2 legends for expansion of abbreviations.

Table Graphic Jump Location
TABLE 4 ]  Characteristics of Patients Positive for LGE

See Table 1 and 2 legends for expansion of abbreviations.

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