Cardiac Sarcoidosis Group Research Articles

Role of Textural Analysis Parameters Derived from FDG PET/CT in Diagnosing Cardiac Sarcoidosis

Abstract Introduction Texture and radiomic analysis characterize the lesion's phenotype and evaluate its microenvironment in quantitative terms. The aim of this study was to investigate the role of textural features of 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography–computed tomography (PET/CT) images in differentiating patients with cardiac sarcoidosis (CS) from patients with physiologic myocardial uptake. Methods This is a retrospective, single-center study of 67 patients, 17 diagnosed CS patients, and 50 non-CS patients. These patients underwent FDG PET/CT for the diagnosis of CS. The non-CS group underwent 18F-FDG PET/CT for other oncological indications. The PET/CT images were then processed in a commercially available textural analysis software. Region of interest was drawn over primary tumor with a 40% threshold and was processed further to derive 92 textural and radiomic parameters. These parameters were then compared between the CS group and the non-CS group. Receiver operating characteristics (ROC) curves were used to identify cutoff values for textural features with a p-value < 0.05 for statistical significance. These parameters were then passed through a principle component analysis algorithm. Five different machine learning classifiers were then tested on the derived parameters. Results A retrospective study of 67 patients, 17 diagnosed CS patients, and 50 non-CS patients, was done. Twelve textural analysis parameters were significant in differentiating between the CS group and the non-CS group. Cutoff values were calculated for these parameters according to the ROC curves. The parameters were Discretized_HISTO_Entropy, GLCM_Homogeneity, GLCM_Energy, GLRLM_LRE, GLRLM_LGRE, GLRLM_SRLGE, GLRLM_LRLGE, NGLDM_Coarseness, GLZLM_LZE, GLZLM_LGZE, GLZLM_SZLGE, and GLZLM_LZLGE. The gradient boosting classifier gave best results on these parameters with 85.71% accuracy and an F1 score of 0.86 (max 1.0) on both classes, indicating the classifier is performing well on both classes. Conclusion Textural analysis parameters could successfully differentiate between the CS and non-CS groups noninvasively. Larger multicenter studies are needed for better clinical prognostication of these parameters.

Electrocardiographic features in the early differential diagnosis of cardiac amyloidosis from cardiac sarcoidosis

Abstract Introduction Amyloidosis and sarcoidosis are both systemic infiltrative diseases which can cause cardiac involvement. Differentiating early-stage cardiac amyloidosis (CA) from cardiac sarcoidosis (CS) is still challenging, although hypertrophy for CA and septal thinning for CS are characteristic echocardiographic findings in each late-stage. The diagnosis is a time-sensitive issue, given the therapies for CA and CS likely to be effective at early disease stages. Purpose We aimed to evaluate the utility of electrocardiography (ECG) for distinguishing CA from CS before or early in the course of cardiomyopathy. Methods This study enrolled 36 consecutive patients (20 male, 75±13 years) diagnosed with transthyretin-CA in 25 (CA group) and isolated CS in 11 patients (CS group) according to accepted criteria at our institute from July 2014 to July 2023. We retrospectively reviewed electrocardiographic characteristics and clinical outcomes of early-stage CA and CS. Results The CS group were younger than the CA group at the time of diagnosis (59±9 vs 83±7 years, P<0.01) and had a shorter period between the date of their first ECG recording at our institute and the date of diagnosis (18±3 vs 62±67 months, P=0.012). Furthermore, the CA group showed specific P-waves with longer duration (142±19 vs 126±8 ms, P=0.003) and more notches and/or fragmentation (91% vs 33%, P=0.003) in the limb leads on the initial ECG than the CS group, although prolonged PR-interval is common in both CA and CS (191±44 vs. 208±43 ms, P=0.359). Unexpectedly, the CA group had a shorter QRS duration (103±25 vs 123±31 ms, P=0.047) and a higher R-wave in V5 (2.0±0.9 vs 1.3±1.1 mV, P=0.039) than the CS group. In addition, the low voltage in all limb leads, pseudoinfarct pattern and bundle branch block morphology characteristic of CA patients did not differ between diagnosis and initial examination. There were also no differences in atrial and ventricular arrhythmias. During the follow-up period, 5 patients (20%) in the CA group, but no patients in the CS group died. Conclusion CA and CS shares several electrocardiographic features. Prolonged P-wave with notches and fragmentation, suggesting atrial conduction disturbance, may be associated with amyloid deposition in CA. This finding might be useful in the early differential diagnosis for CA from CS.

Abstract 13629: Increased Rate of High Risk Cardiac Outcomes in Patients With Cardiac Sarcoidosis Without Underlying Coronary Artery Disease: Analysis of the National Inpatient Sample From 2015-2019

Introduction: Sarcoidosis is a systemic disease characterized by deposition of noncaseating granulomas. It commonly involves the lungs but can also affect other organs such as the heart. In terms of cardiac sarcoidosis, it is still a relatively under diagnosed illness with its clinical manifestations often being variable and nonspecific thus making the diagnosis challenging. There is a need to further investigate the burden of high-risk cardiac outcomes in patients with underlying sarcoidosis with cardiac involvement to further understand the extent of disease progression in this group. Methods: In this study, the National Inpatient Sample (NIS) was queried for the years 2015 Q4-2019. Our cohort of interest included patients with Sarcoidosis, more specifically, those with cardiac involvement. Patients with underlying coronary artery disease and its equivalents were excluded from the study. Multivariate logistic with linear regression analysis was used to adjust for confounders. Results: After excluding patients with coronary artery disease (CAD) equivalents, the final number of patients included in the study was 8,722,809. Out of which, 54,537 had sarcoidosis with a total of 918 having a diagnosis of cardiac sarcoidosis (CS). Patients with CS were more likely to be males and be younger than 65 (p<0.001). African American race was the predominant population affected in both cohorts (p<0.001). The CS group had higher rates of underlying congestive heart failure but were overall less likely to have underlying connective tissue disease, chronic pulmonary disease, and diabetes (p<0.001). In terms of cardiac outcomes, they had higher rates of Cardiac Arrest (2.2% vs 0.7%, p<0.001), Atrial Fibrillation (24.5% vs 10.4%, p<0.001), Ventricular Tachycardia (36.6% vs 2.0%, p<0.001), AV Block Type 3 (10.3% vs 0.7%, p<0.001) and Heart Failure [systolic HF (54.6% vs 6.6%, p<0.001), diastolic HF (20.9% vs 12.3%, p<0.001)]. Conclusions: We demonstrate with the results of this study that patients with cardiac sarcoidosis had higher rates of major arrhythmias, conduction defects, and cardiac arrest. Understanding these associations may help in earlier clinical diagnosis and possibly improved outcomes with targeted therapies.

Cardiac sarcoidosis outcome differences: A comparison of patients with de novo cardiac versus known extracardiac sarcoidosis at presentation

BackgroundSarcoidosis is a systemic disease characterized by granulomatous inflammation. Cardiac involvement is associated with increased morbidity. However, differences in clinical characteristics and outcomes based on initial sarcoidosis organ manifestation in patients with cardiac sarcoidosis (CS) have not been described. MethodsA retrospective cohort of 252 patients with CS at an urban, quaternary medical center was studied. Presentation, treatment and outcomes of de novo CS and prior ECS groups were compared. Survival free of primary composite outcome (left ventricular assist device implantation, orthotopic heart transplantation (OHT), or death) was assessed. ResultsThere were 124 de novo CS patients and 128 with prior ECS at time of CS diagnosis. De novo CS patients were younger at CS diagnosis (p = 0.020). De novo CS patients had a more advanced cardiac presentation: lower left ventricular ejection fraction (LVEF) (p < 0.001), more frequent sustained ventricular arrhythmias (VA) (p = 0.001), and complete heart block (p = 0.001). During follow-up, new VA (p < 0.001), ventricular tachycardia ablation (p < 0.001), and OHT (p = 0.003) were more common in the de novo CS group. Outcome free survival was significantly shorter for de novo CS patients (p = 0.005), with increased hazard of primary composite outcome (p = 0.034) and development of new VA (p = 0.027) when compared to ECS patients. Overall mortality was similar between groups. ConclusionPatients presenting with CS as their first recognized organ manifestation of sarcoidosis have an increased risk of adverse cardiac outcomes as compared to those with a prior history of ECS. Improved awareness and diagnosis of CS is warranted for earlier recognition.

Variable Phenotypes At Initial Presentation Of Cardiac Sarcoidosis: A Comparison Of De Novo Cardiac Sarcoidosis Versus Prior Extracardiac Sarcoidosis

Background Sarcoidosis is an inflammatory granulomatous disease that can affect several organs. Cardiac involvement is increasingly prevalent. However, characteristics of patients who present de novo with cardiac sarcoidosis (CS) compared to those diagnosed with CS after prior extracardiac sarcoidosis (ECS) diagnosis have not been studied. Methods : A retrospective cohort of 253 CS patients from 2000-2020 at an urban, quaternary medical center was studied. Medical records were reviewed for initial CS presentation, management, and outcomes. Differences (two sample t-test, chi-squared test, or Fisher's exact test) between de novo CS and prior ECS groups were analyzed. Results : There were 124 (49%) de novo CS patients and 129 (51%) with prior ECS at time of CS diagnosis (Table). De novo CS patients were more likely to meet Heart Rhythm Society definite CS criteria (P<0.001) and were diagnosed and started immunosuppression for CS at a younger age (p=0.001 and p=0.003, respectively). De novo CS patients had a more advanced cardiac presentation at CS diagnosis, with lower left ventricular ejection fraction (LVEF) (p<0.001), more frequent ventricular tachycardia/fibrillation (p<0.001), heart failure (p=0.052), reduced LVEF<50% (p=0.004), and complete heart block (p=0.001). As for treatment, de novo CS patients received prednisone at a higher frequency (p<0.001) and dose (p=0.011) compared to patients with prior ECS. Steroid sparing agent (SSA) frequency was similar with mycophenolate mofetil used more commonly among de novo CS patients. During follow-up, new VT, VT ablation, LVAD implantation, and heart transplantation were more common in the de novo CS group. LVEF recovery was less common in this group while mortality was similar. Conclusions : Patients diagnosed with de novo CS were younger, with more advanced cardiac presentation and worse clinical outcomes when compared to those presenting with CS after known ECS. These findings highlight the importance of upfront consideration of CS as a cause of unexplained heart block, arrhythmia, or cardiomyopathy to ensure timely treatment and prevention of advanced heart failure. One cannot wait for a diagnosis of ECS to consider CS. Sarcoidosis is an inflammatory granulomatous disease that can affect several organs. Cardiac involvement is increasingly prevalent. However, characteristics of patients who present de novo with cardiac sarcoidosis (CS) compared to those diagnosed with CS after prior extracardiac sarcoidosis (ECS) diagnosis have not been studied. : A retrospective cohort of 253 CS patients from 2000-2020 at an urban, quaternary medical center was studied. Medical records were reviewed for initial CS presentation, management, and outcomes. Differences (two sample t-test, chi-squared test, or Fisher's exact test) between de novo CS and prior ECS groups were analyzed. : There were 124 (49%) de novo CS patients and 129 (51%) with prior ECS at time of CS diagnosis (Table). De novo CS patients were more likely to meet Heart Rhythm Society definite CS criteria (P<0.001) and were diagnosed and started immunosuppression for CS at a younger age (p=0.001 and p=0.003, respectively). De novo CS patients had a more advanced cardiac presentation at CS diagnosis, with lower left ventricular ejection fraction (LVEF) (p<0.001), more frequent ventricular tachycardia/fibrillation (p<0.001), heart failure (p=0.052), reduced LVEF<50% (p=0.004), and complete heart block (p=0.001). As for treatment, de novo CS patients received prednisone at a higher frequency (p<0.001) and dose (p=0.011) compared to patients with prior ECS. Steroid sparing agent (SSA) frequency was similar with mycophenolate mofetil used more commonly among de novo CS patients. During follow-up, new VT, VT ablation, LVAD implantation, and heart transplantation were more common in the de novo CS group. LVEF recovery was less common in this group while mortality was similar. : Patients diagnosed with de novo CS were younger, with more advanced cardiac presentation and worse clinical outcomes when compared to those presenting with CS after known ECS. These findings highlight the importance of upfront consideration of CS as a cause of unexplained heart block, arrhythmia, or cardiomyopathy to ensure timely treatment and prevention of advanced heart failure. One cannot wait for a diagnosis of ECS to consider CS.

Efficacy of myocardial washout of 99mTc-MIBI/Tetrofosmin for the evaluation of inflammation in patients with cardiac sarcoidosis: comparison with 18F-fluorodeoxyglucose positron emission tomography findings.

Both myocardial perfusion scintigraphy and 18F-fluorodeoxyglucose positron emission tomography (FDG PET) are useful for the diagnosis of cardiac sarcoidosis (CS). However, the association between the washout of 99mTc-labeled tracer and FDG PET has not been established. This study aimed to evaluate the association between the washout of 99mTc-labeled tracer and FDG PET findings in patients with CS. We retrospectively analyzed 64 patients (65.0 ± 11.2years, 53% male) with suspected CS who underwent myocardial single-photon emission computed tomography (SPECT) with 99mTc-labeled tracer and FDG PET. The SPECT images were acquired at 15min (early images) and 3h (delayed images) after injection and scored visually using a 17-segment model with a 5-point scoring system. The washout score was defined as the difference between the early and delayed total defect scores. FDG positivity was considered as focal or focal on diffuse patterns on visual assessment, and FDG uptake was quantified by measuring the standardized uptake value (SUV) of each of the 17 segments. The washout score was significantly higher for the CS group than for the non-CS group (3.0 [-1.0-5.0] vs. 0.0 [-0.5-1.0], p = 0.010). Receiver operating characteristic analysis showed that a washout score of ≥ 2 had the best accuracy for detecting CS (88% sensitivity and 56% specificity) and FDG positivity (71% sensitivity and 89% specificity). In the segment-based analysis of 833 segments from 49 patients, excluding 15 patients with diffuse FDG uptake, the median SUVs for FDG uptake for the washout scores of ≤ 0, 1, and 2 were 2.3 (1.8-3.6), 4.2 (2.9-7.8), and 8.3 (6.5-9.4), respectively (p < 0.001). The washout of 99mTc-labeled tracer can be a useful marker for the evaluation of FDG PET findings in patients with CS.

Idiopathic giant cell myocarditis or cardiac sarcoidosis? A retrospective audit of a nationwide case series.

AimsCardiac sarcoidosis (CS) and giant cell myocarditis (GCM) are inflammatory cardiomyopathies sharing histopathological and clinical features. Their differentiation is difficult and susceptible of confusion and apparent mistakes. The possibility that they represent different phenotypes of a single disease has been debated.Methods and resultsWe made a retrospective audit of 73 cases of GCM diagnosed in Finland since the late 1980s. All available histological material was reanalyzed as were other examinations pertinent to the distinction between GCM and CS. Finding granulomas in or outside the heart was considered diagnostic of CS and exclusive of GCM. Altogether 45 of the 73 cases of GCM (62%) were reclassified as CS. In all except one case, this was based on finding sarcoid granulomas that either had been originally missed (n = 29) or misinterpreted (n = 11) or were found in additional posttransplant myocardial specimens (n = 3) or samples of extracardiac tissue (n = 1) accrued over the disease course. Supporting the reclassification, patients relocated to the CS group had less heart failure at presentation (prevalence 20% vs. 46%, P = 0.017) and better 1 year transplant‐free survival (82% vs. 45%, P = 0.011) than patients considered to represent true GCM.ConclusionsRecognizing granulomas in or outside the heart remains a challenge for the pathologist. Given that CS and GCM are considered distinct diseases and granulomas exclusive of GCM, many cases of GCM, if thoroughly scrutinized, may need reclassification as CS. However, whether CS and GCM are truly different entities or parts of a one‐disease continuum has not yet been conclusively settled.

Cardiac sarcoidosis: worse pulmonary function due to left ventricular ejection fraction?: A case-control study.

Dyspnea and exercise intolerance are usually attributed to pulmonary disease in sarcoidosis patients. However, cardiac involvement may also be responsible for these symptoms. Data regarding the impact of heart involvement on lung function in cardiac sarcoidosis (CS) is limited.The aim of study was to compare the results of pulmonary function tests (PFTs) in patients with and without heart involvement. We performed a retrospective analysis of PFTs in a group of sarcoidosis patients both with and without heart involvement evaluated by cardiovascular magnetic resonance (CMR) study. The study was performed in the period between May 2008 and April 2016.We included data of sarcoidosis patients who underwent testing for possible CS (including CMR study) at a national tertiary referral center for patients with interstitial lung diseases. All patients had histopathologicaly confirmed sarcoidosis and underwent standard evaluation with PFTs measurements including spirometry, plethysmography, lung transfer factor (TL,CO), and 6-minute walking test (6MWT) assessed using the most recent predicted values.We identified 255 sarcoidosis patients (93 women, age 42 ± 10.7 y): 103 with CS and 152 without CS (controls). CS patients had significantly lower left ventricular ejection fraction (LVEF; 56.9 ± 7.0 vs 60.4 ± 5.4, P < .001). Any type of lung dysfunction was seen in 63% of CS patients compared with 31% in the controls (P = .005). Ventilatory disturbances (obstructive or restrictive pattern) and low TL,CO were more frequent in CS group (52% vs 23%, P < .001 and 38% vs 18% P < .01 respectively). CS (OR = 2.13, 95% CI: 1.11–4.07, P = .02), stage of the disease (OR = 3.13, 95% CI: 1.4–7.0, P = .006) and LVEF (coefficient = –0.068 ± 0.027, P = .011) were independent factors associated with low FEV1 but not low TL,CO. There was a significant correlation between LVEF and FEV1 in CS group (r = 0.31, n = 89, P = .003). No significant difference in 6MWD between CS patients and controls was observed.Lung function impairment was more frequent in CS. Lower LVEF was associated with decreased values of FEV1. Relatively poor lung function may be an indication of cardiac sarcoidosis.

CLINICAL RISK FACTORS FOR CARDIAC SARCOIDOSIS

SESSION TITLE: Wednesday Abstract Posters SESSION TYPE: Original Investigation Posters PRESENTED ON: 10/23/2019 09:45 AM - 10:45 AM PURPOSE: Identification of risk factors associated with cardiac sarcoidosis. METHODS: Retrospective case control study with prospective follow up including 598 patients with biopsy proven sarcoidosis involving multi organs except cardiac involvement and 32 patients with cardiac sarcoidosis. Thorough chart review was done for all the cases and controls and data was collected for variables including demographics, diagnostic studies and treatment details. RESULTS: Univariate analysis was done using the SPSS program. There were no significant statistical differences for age, race, gender (P >0.05). We found significant differences between group in FEV1 % (p =0.022), FEV1/FVC (p=0.012), whereas there were no differences in FVC, DLCO, TLC (P value >0.05). We found significant difference in CRP (P=0.000), while ACE and Pro-BNP levels (p>0.05) were not significant. RVSP was elevated in cardiac sarcoidosis group (p= 0.011). Furthermore, OSA (P =0.002) and DM (p=0.000) were found to be associated with cardiac sarcoidosis. Patients with cardiac sarcoidosis were on long term oxygen therapy (P=0.000). However, co morbidities including asthma, HTN, anemia were not statistically significant (p>0.05) CONCLUSIONS: Elevated CRP levels, worsening lung volumes including FEV1/FVC and FEV1, long term oxygen therapy, OSA and DM and elevated RVSP on transthoracic echo are associated with cardiac sarcoidosis. CLINICAL IMPLICATIONS: CRP values can be used as an early diagnostic marker for cardiac sarcoidosis. Patients with OSA, elevated RVSP on TTE, those on Long term oxygen therapy and with worsening lung volumes on PFT’s could be monitored closely for progression to cardiac sarcoidosis, hence decreasing the incidence of sudden cardiac death associated with Cardiac sarcoidosis. DISCLOSURES: No relevant relationships by asil daoud, source=Web Response No relevant relationships by Amina Pervaiz, source=Web Response No relevant relationships by Lobelia Samavati, source=Web Response

Absence of Pre-Transplant Pulmonary Features of Sarcoidosis is of Low Negative Predictive Value in End-Stage Cardiac Sarcoidosis

Purpose Cardiac sarcoidosis is a potentially reversible etiology of heart failure if identified and managed in a timely fashion. Given the multisystem nature of the disease and need for a high index of suspicion, diagnosis of cardiac sarcoidosis is difficult, and the underlying cause remains speculative. Methods In a single-center retrospective case-control study of 15 patients with pathologic evidence of cardiac sarcoidosis that required cardiac transplantation or left ventricular assist device placement, diagnosed by diagnostic granulomas on native heart cardiectomy or apical core, and 33 matched controls, we collected pre-transplant pulmonary function testing (PFT) and right heart catheterization (RHC) data. We performed a blinded review of pre-transplant chest CT to categorize each scan as likely, possible, or unlikely for sarcoidosis. Results Mean age in the cardiac sarcoidosis group was 59 years and 67% were male. The FVC, FEV1, TLC, and DLCO were similar in both groups. RHC showed comparable hemodynamics with a non-significant trend towards lower cardiac index and lower mixed venous O2 saturation in the sarcoidosis group. Figure 1 shows the distribution of chest CT interpretation. Sensitivity and specificity of the chest CT classification in predicting cardiac sarcoidosis were 0.79 and 0.38, respectively, with positive predictive value of 0.41 (95%CI, 0.22-0.61) and negative predictive value of 0.77 (0.46-0.95). Conclusion PFT and RHC data did not independently differentiate the likelihood of cardiac sarcoidosis in our sample. Chest CT scans may identify patients with nonischemic heart failure who need to be considered for workup of cardiac sarcoidosis. However, absence of clear pulmonary radiographic or PFT finding at the time of tertiary referral did not exclude the diagnosis. It remains unclear whether sarcoidosis with end-stage physiology limited to the heart represents a distinct pathological entity from pulmonary-predominant sarcoidosis.

Abstract 17103: A Novel Approach to an Old and Unrecognized Disease- Intricacies of Cardiac Sarcoidosis

Introduction: Appropriate referral of patients to advanced imaging for suspected cardiac sarcoidosis (CS), and prognosis of patients based on imaging results is not well understood. We sought to define clinical predictors associated with an imaging diagnosis of CS and compare outcomes in the CS group, based on imaging characteristics Methods: Study population comprised 164 consecutive patients, referred for FDG-PET or MRI imaging based on clinical suspicion for CS. Imaging diagnosis of CS was based on prior MRI results or current FDG-PET results, classified as scar+ inflammation (group1), scar-only (group2) and inflammation-only (group3). Follow-up was 2.3±1.3 years Results: Among 164 patients, 61% were male (mean age 59±10 years, 82% white) and 86 (52%) were diagnosed as CS (68 by PET and 18 by MRI). Clinical presentation of VT (32/86-37% vs 7/78-10%) and conduction system disease i.e. AV block and sinus node dysfunction (14/86-16% vs 6/78-6%) was more likely in CS (p&lt;0.05). Prior diagnosis of extracardiac sarcoid was less frequent in CS (49% vs 69% p=0.03). LVEF was similar in both groups (45±18 in CS vs 51±19 in controls). In a multivariable model including the above variables, presentation with VT (OR5.64; CI-1.98-16.10) and conduction system disease (OR 2.13; CI-1.03-9.94) remained significant predictors of imaging diagnosis of CS. The distribution of FDG-PET results was: Group 1 (29%), Group 2 (32%) and Group 3 (38%). Group 1 had the highest incidence of VT at presentation (55% vs 41% vs 19%). Mean LVEF was 44±14, 23±14 and 52±12 across 3 groups respectively (p&lt;0.003). Steroids and immunosuppressants were more commonly used in Groups 1 and 3 vs 2 (75%, 69% vs 18% p&lt;0.0001). In a multivariable model that included LVEF and presentation with VT/conduction system disease, use of immunosuppressants (OR 2.57; CI 1.05-6.25) and LVEF (OR 0.97; CI 0.94-0.99) significantly predicted the outcome of death or recurrent VT (chi-sq 9.57; p=0.008) Conclusions: In a population being referred for imaging diagnosis of CS, presentation with VT or conduction system disease is more likely to identify those with disease. Among those with imaging diagnosis of CS by FDG-PET, presence of inflammation and therefore use of immunosuppressants and low LVEF were predictive of death or VT.

Use of 18F-FDG PET/CT texture analysis to diagnose cardiac sarcoidosis.

18F-fluorodeoxyglocose positron emission tomography (FDG PET) plays a significant role in the diagnosis of cardiac sarcoidosis (CS). Texture analysis is a group of computational methods for evaluating the inhomogeneity among adjacent pixels or voxels. We investigated whether texture analysis applied to myocardial FDG uptake has diagnostic value in patients with CS. Thirty-seven CS patients (CS group), and 52 patients who underwent FDG PET/CT to detect malignant tumors with any FDG cardiac uptake (non-CS group) were studied. A total of 36 texture features from the histogram, gray-level co-occurrence matrix (GLCM), gray-level run length matrix (GLRLM), gray-level zone size matrix (GLZSM) and neighborhood gray-level difference matrix (NGLDM), were computed using polar map images. First, the inter-operator and inter-scan reproducibility of the texture features of the CS group were evaluated. Then, texture features of the patients with CS were compared to those without CS lesions. Twenty-eight of the 36 texture features showed high inter-operator reproducibility with intraclass correlation coefficients (ICCs) over 0.80. In addition, 17 of the 36 showed high inter-scan reproducibility with ICCs over 0.80. The SUVmax showed no difference between the CS and non-CS group [7.36 ± 2.77 vs. 8.78 ± 4.65, p= 0.45, area under the curve (AUC) = 0.60]. By contrast, 16 of the 36 texture features could distinguish CS from non-CS grsoup with AUC > 0.80. Multivariate logistic regression analysis after hierarchical clustering concluded that long-run emphasis (LRE; P= 0.0004) and short-run low gray-level emphasis (SRLGE; P= 0.016) were significant independent factors that could distinguish between the CS and non-CS groups. Specifically, LRE was significantly higher in CS than in non-CS (30.1 ± 25.4 vs. 11.4 ± 4.6, P< 0.0001), with high diagnostic ability (AUC = 0.91), and had high inter-operator reproducibility (ICC = 0.98). The texture analysis had high inter-operator and high inter-scan reproducibility. Some of texture features showed higher diagnostic value than SUVmax for CS diagnosis. Therefore, texture analysis may have a role in semi-automated systems for diagnosing CS.

Invasive Hemodynamics and Rejection Rates in Patients With Cardiac Sarcoidosis After Heart Transplantation

BackgroundOrthotopic heart transplant (OHT) is increasingly used for end-stage heart failure due to cardiac sarcoidosis (CS). However, concern regarding long-term outcomes in patients with CS after OHT persists because of multiorgan involvement. MethodsBaseline demographics and invasive hemodynamics were measured in 12 patients with CS and 28 patients with nonischemic cardiomyopathy requiring OHT at the time of transplantation, 1 week after OHT, and in routine follow-up. Primary endpoints included changes in pulmonary artery pressure, right ventricular stroke work index, and pulmonary compliance. Secondary endpoints included degree of allograft rejection and death. ResultsDuring a mean follow-up of 73.8 months, no differences in pulmonary artery pressures, right ventricular stroke work index, or cardiac index were observed in patient with CS (n = 12) compared with those without CS (n = 28) between 1 week after OHT and the most recent follow-up. Long-term follow-up showed that pulmonary hemodynamics remained normal in the CS group. International Society for Heart and Lung Transplantation (ISHLT) 1990 grade ≥ 1a rejection occurred less frequently in the CS group (17% vs 68%, P = 0.006), and 0 of 12 patients in the CS group experienced histologic or clinical recurrence of sarcoidosis or ≥2 rejection. Patients with CS had excellent survival after OHT, with 0 deaths or significant rejection. ConclusionsPatients with CS have similar post-transplant hemodynamics as patients without CS, without evidence of right ventricular dysfunction or pulmonary hypertension. Neither significant rejection nor recurrence of sarcoid in the allograft was observed in this cohort of patients with CS. Survival is similar between patients with CS and those without CS. Heart transplant is a viable strategy in selected patients with CS with excellent outcomes.

Contrast-enhanced cardiac Magnetic Resonance: distinction between cardiac sarcoidosis and infarction scar.

Objectives: To review the value of delayed contrast-enhanced cardiac magnetic resonance (CECMR) in differentiating patients with cardiac sarcoidosis (CS) from those with coronary artery disease and recent myocardial infarctions. Background: Late gadolinium enhancement (LGE) accurately delineates myocardial necrosis or fibrosis. The pattern of LGE in ischemic and non-ischemic myocardial disease is different, and might be helpful in distinguishing CS from ischemic disease. Methods: The CECMR studies of 30 patients with CS were compared to those performed in 30 consecutive infarct patients, who had been managed with primary coronary interventions, and 10 healthy controls. Two experienced blinded observers classified patients by assessing the distribution of LGE. Results: LV LGE was present in 29/30 CS (mean 3.8 segments, range 0-12), all infarct (mean 4.3 segments, range 0-9), and none of the patients in the control group. The amount of LV LGE did not differ significantly between CS and infarct patients (19 ± 11% and 19 ± 12%, P= 0.8). The CS group exhibited a predominantly patchy, 3 layer LGE (P = 0.01), whereas confluent transmural LGE (P = 0.04) with a vascular distribution (P < 0.001) was prevalent in the infarct group. Significantly more RV LGE (P = 0.01) and dilation (P = 0.02) were found in the CS group. The two observers classified patients correctly as CS in 72% and 83% of cases, as ischemic in nature in 77% and 80% of cases, and as normal in 90% and 100% respectively. Conclusions: Gadolinium CMR was helpful in differentiating patients with CS from patients with ischemic heart disease and previous myocardial infarctions. In a subgroup of ischemic patients the pattern of LGE was atypical, and suggestive of non-ischemic etiology. (Sarcoidosis Vasc Diffuse Lung Dis 2017; 34: 307-314).

An oxidative stress biomarker, urinary 8-hydroxy-2′-deoxyguanosine, predicts cardiovascular-related death after steroid therapy for patients with active cardiac sarcoidosis

BackgroundWe investigated whether urinary 8-hydroxy-2′-deoxyguanosine (U-8-OHdG), a marker of oxidative DNA damage, is a prognosticator of cardiovascular-related death in patients with cardiac sarcoidosis (CS). Methods and resultsIn this prospective study, 30 consecutive patients were divided into the active CS (n=20) and non-active CS (n=10) groups, based on abnormal isotope accumulation in the heart on 18F-fluorodeoxyglucose positron-emission tomography/computed tomography (18F-FDG PET/CT) imaging. Nineteen patients in the active CS group underwent corticosteroid therapy. Before corticosteroid therapy initiation, U-8-OHdG, brain natriuretic peptide (BNP), other biomarkers, and indices of cardiac function were measured. Patients were followed-up for a median of 48months. The primary endpoint was the incidence of cardiovascular-related death.During the follow-up period, in the corticosteroid-treated active CS group, 7 of 19 patients experienced cardiovascular-related death. By contrast, in the non-active CS group, 1 of 10 patients died from cardiovascular-related causes. Univariate and multivariate analyses showed that U-8-OHdG and BNP were independent predictors for cardiovascular-related death. The cut-off values for predicting cardiovascular death in corticosteroid-treated patients with active CS were 19.1ng/mg·Cr and 209pg/mL for U-8-OHdG and BNP, respectively. Patients with a U-8-OHdG concentration ≥19.1ng/mg·Cr or a BNP concentration ≥209pg/mL had a significantly higher cardiovascular-related death risk, but U-8-OHdG had better predictive value compared with BNP. ConclusionThese findings suggested that U-8-OHdG was a powerful predictor of cardiovascular-related death in patients with CS, suggesting that active CS patients with elevated U-8-OHdG levels might be resistant to corticosteroid therapy.

Non-Invasive Detection of Latent Cardiac Conduction Abnormalities in Patients With Pulmonary Sarcoidosis Application of Signal Averaged Electrocardiogram

Electrocardiographic conduction abnormalities including development of atrioventricular block, bundle branch block or ventricular arrhythmias are characteristic manifestations of cardiac sarcoidosis (CS). The present study seeks to show the minute conduction abnormality by detection of late potentials (LP) on signal averaged electrocardiogram (SAECG). Ten patients with CS, 52 patients with pulmonary sarcoidosis (PS) but no obvious cardiac manifestations and 52 normal controls were studied. All participants underwent SAECG to detect LP. In patients with CS (the CS group), LP were detected in 8 patients (80%). In 52 patients with PS, LP were detected in 25 patients (46.2%, PS-LP(+) group), comparing only 3 (5.8%) of normal controls (p<0.0001). The remaining 27 patients with PS with negative LP were classified in the PS-LP(-) group. In the CS group, premature ventricular contraction frequency on Holter's monitoring and plasma B-type natriuretic peptide concentrations were significantly higher than those in the PS group. However, no significant difference in these parameters between PS-LP(+) and PS-LP(-) groups were found. In the PS patients without obvious cardiac manifestations, LP were detected as high as 46.2%, suggesting latent minute conduction abnormality. The higher incidence of LP in PS might be considered as an expression of latent myocardial fibrosis. Close follow-up is needed in these patients.

QT Dispersion in Sarcoidosis

QT dispersion (QTd) is the maximal interlead difference in QT interval on surface 12-lead ECG. An increase in QTd is found in various cardiac diseases. Sarcoidosis augments inhomogeneity in ventricular repolarization by sarcoid granuloma, which significantly correlates with ventricular fibrillation. Changes in QTd in the course of sarcoidosis have not been investigated previously. The study included 35 patients with systemic sarcoidosis. The diagnosis of systemic sarcoidosis was made by biopsy. Thallium scintigraphy was performed in all patients with systemic sarcoidosis. Cardiac sarcoidosis was diagnosed in 16 patients based on abnormal thallium scintigraphy and normal coronary arteriography results. QTd, corrected QTd (cQTd), maximum QT (QTmax), maximum corrected QT (cQTmax), minimum QT, and minimum corrected QT intervals were measured. Twenty-four healthy subjects represented the control group for QT interval analysis. In the cardiac sarcoidosis group, mean QTd (+/- SD) was significantly greater than in the noncardiac sarcoidosis group and control group (49.50 +/- 10.86 ms, 28.14 +/- 11.02 ms, and 27.08 +/- 10.41 ms, respectively; p < 0.001). cQTd was significantly greater in the cardiac sarcoidosis group than in the noncardiac sarcoidosis group and control group (53.17 +/- 10.44 ms, 30.61 +/- 10.94 ms, and 29.01 +/- 10.52 ms, respectively; p < 0.001). QTmax (440 +/- 15.01 ms, 409 +/- 14.86 ms, and 410 +/- 13.21 ms; p < 0.001) and cQTmax (449 +/- 16.31 ms, 417 +/- 12.51 ms, and 418 +/- 11.76, respectively; p < 0.001) were also significantly greater in patients with cardiac sarcoidosis. In a limited follow-up group (11 cardiac and 9 noncardiac sarcoidosis patients), the incidence of premature ventricular contraction (PVC) on ECG was greater in the cardiac sarcoidosis group than in the noncardiac sarcoidosis group (36% and 0%, respectively; p < 0.05). A medium correlation existed between QTd and PVC (r = 0.331, p < 0.05). QTd, cQTd, QTmax, and cQTmax are prolonged in patients with cardiac sarcoidosis compared to the patients with noncardiac sarcoidosis and control subjects. The incidence of PVC on ECG was greater in the cardiac sarcoidosis group than in the noncardiac sarcoidosis group.

A clinical and histopathologic comparison of cardiac sarcoidosis and idiopathic giant cell myocarditis

ObjectivesThe goal of this study was to determine the prognostic value of clinical data available at presentation and histology in cardiac sarcoidosis (CS) and idiopathic giant cell myocarditis (IGCM). BackgroundThe prognosis of patients with nonischemic cardiomyopathy is partly dependent on the histologic diagnosis. Survival in IGCM is poor. The prognosis of a histologically related entity, cardiac sarcoidosis (CS), is less well established, and the prognostic value of the distinction between CS and IGCM on endomyocardial biopsy (EMB) is unknown. MethodsWe identified 115 patients from the Multicenter IGCM Registry with CS (n = 42) and IGCM (n = 73). We compared the clinical data for these two groups using Cox proportional-hazards models to assess the association between histologic diagnosis and survival. In order to determine whether histologic features could reliably differentiate these two entities, two cardiac pathologists semiquantitatively graded the inflammatory infiltrate components and compared the results between groups. ResultsBlack race was more frequent in the CS group (31% vs. 4%, p < 0.0001). Syncope and atrioventricular block were also more frequently observed in CS than IGCM (31% vs. 5%, p = 0.0002 and 50% vs. 15%, p < 0.0001, respectively). Left-sided heart failure was more common in IGCM (40% vs. 64%, p = 0.013). In CS patients diagnosed by EMB, the five-year transplant-free survival after diagnosis was 69.8% versus 21.9% for IGCM (p < 0.0001, log-rank test). In multivariate models, presentation with heart failure predicted IGCM, and presentation with heart block or more than nine weeks of symptoms predicted CS. Eosinophils, myocyte damage, and foci of lymphocytic myocarditis were more frequent in IGCM, while granulomas and fibrosis were more frequent in CS. ConclusionsTransplant-free survival is better for patients with CS than for IGCM diagnosed by EMB. Presentation with heart failure predicted IGCM, and presentation with heart block or more than nine weeks of symptoms predicted CS.