Cardiac Sarcoidosis Patients Research Articles

Combination Therapy With Mycophenolate Mofetil And Prednisone In The Treatment Of Cardiac Sarcoidosis

Introduction Long-term immunosuppression is the mainstay of treatment for cardiac sarcoidosis (CS). While steroids are the cornerstone of therapy, steroid-sparing alternatives are considered second-line or adjunctive in the management of CS. We aimed to evaluate the efficacy of mycophenolate mofetil and steroids on the clinical and radiographic outcomes of patients with CS. Methods A retrospective chart review at a single academic medical center of patients with CS that were treated with prednisone or combination therapy with prednisone and MMF was conducted between 2019-2021. Baseline demographics, clinical data, echocardiography and PET data was collected pre and post-treatment. Improvement in disease was based on improvement in left ventricular ejection fraction (LVEF), reduction of arrhythmia burden, and regional maximum Standardized Uptake Value and percentage of inflammation on 18F-fluorodeoxyglucose positron emission tomography (FDG-PET). The parameters were then compared between the MMF and non- MMF group. Results There were 19 total patients (63% male and 52% black that were found to have CS- of which 7 had a positive cardiac or extracardiac biopsy. 17 patients were treated with combination therapy consisting of prednisone and MMF. Median follow-up between scans was 154 days in MMF group and 156.5 days in the non-MMF group. In the MMF group, there was an improvement in EF with a median of 6.5 (p 0.22), regional max SUV decreased by 1.35 (p <0.05) and percent inflammation decreased by a median of 22 percentage points (p 0.11). Of the 14 patients in the MMF group that had an underlying arrhythmia, 11 (78%) had a mitigated or absent arrhythmia burden. In the non-MMF group, the LVEF decreased by a median of 9 (p 0.22), regional max SUV was increased to 1.9 (p <0.05) and percent inflammation decreased by a median of 2 percentage points. 1 of the 2 patients in the non-MMF group showed an improvement in arrhythmia burden. Conclusion CS patients treated with combination therapy consisting of prednisone and MMF appeared to have radiographic and clinical evidence of improvement. MMF may be considered an effective adjunctive therapy to prednisone alone. Long-term immunosuppression is the mainstay of treatment for cardiac sarcoidosis (CS). While steroids are the cornerstone of therapy, steroid-sparing alternatives are considered second-line or adjunctive in the management of CS. We aimed to evaluate the efficacy of mycophenolate mofetil and steroids on the clinical and radiographic outcomes of patients with CS. A retrospective chart review at a single academic medical center of patients with CS that were treated with prednisone or combination therapy with prednisone and MMF was conducted between 2019-2021. Baseline demographics, clinical data, echocardiography and PET data was collected pre and post-treatment. Improvement in disease was based on improvement in left ventricular ejection fraction (LVEF), reduction of arrhythmia burden, and regional maximum Standardized Uptake Value and percentage of inflammation on 18F-fluorodeoxyglucose positron emission tomography (FDG-PET). The parameters were then compared between the MMF and non- MMF group. There were 19 total patients (63% male and 52% black that were found to have CS- of which 7 had a positive cardiac or extracardiac biopsy. 17 patients were treated with combination therapy consisting of prednisone and MMF. Median follow-up between scans was 154 days in MMF group and 156.5 days in the non-MMF group. In the MMF group, there was an improvement in EF with a median of 6.5 (p 0.22), regional max SUV decreased by 1.35 (p <0.05) and percent inflammation decreased by a median of 22 percentage points (p 0.11). Of the 14 patients in the MMF group that had an underlying arrhythmia, 11 (78%) had a mitigated or absent arrhythmia burden. In the non-MMF group, the LVEF decreased by a median of 9 (p 0.22), regional max SUV was increased to 1.9 (p <0.05) and percent inflammation decreased by a median of 2 percentage points. 1 of the 2 patients in the non-MMF group showed an improvement in arrhythmia burden. CS patients treated with combination therapy consisting of prednisone and MMF appeared to have radiographic and clinical evidence of improvement. MMF may be considered an effective adjunctive therapy to prednisone alone.

Localization of Late Gadolinium Enhancement and Its Association with Ventricular Tachycardia in Patients with Cardiac Sarcoidosis.

Sustained ventricular tachycardia (sVT), leading to sudden cardiac death, is one of the common manifestations in cardiac sarcoidosis (CS). Although late gadolinium enhancement (LGE) on cardiac magnetic resonance (CMR) has been reported to be associated with sVT, the relationships of its localization to sVT have not been fully evaluated.To evaluate the localization of LGE and its relationships to sVT in patients with CS, we reviewed medical record of consecutive 31 patients with CS who underwent CMR. The localization of LGE was divided into four categories: Left ventricular (LV) septum, LV free wall, right ventricular (RV) septum, and RV free wall. We investigated the association of sVT with localization of LGE and other parameters including serum biomarkers LV ejection fraction on echocardiography and Fluorine-18-fluorodeoxyglucose (FDG) accumulation on positron emission tomography (PET) -CT.Of the studied population, 8 patients (25.8%) were known to present with sVT among 31 CS patients. LGE was observed in the RV free wall in 6 patients with sVT, whereas it was in 5 patients without sVT (75.0% versus 21.7%, P = 0.022). Univariate analysis showed that only LGE in the RV free wall was associated with sVT (odds ratio [OR]: 10.80; 95% confidence interval [CI]: 1.64-70.93, P = 0.013).LGE in the RV free wall was associated with sVT in patients with CS.

Impact of corticosteroid use on the clinical response and prognosis in patients with cardiac sarcoidosis who underwent an upgrade to cardiac resynchronization therapy.

BackgroundCorticosteroids are widely used in patients with cardiac sarcoidosis (CS). In addition, upgrading to cardiac resynchronization therapy (CRT) is sometimes needed. This study aimed to investigate the impact of corticosteroid use on the clinical outcomes following CRT upgrades.MethodsA total of 48 consecutive patients with non‐ischemic cardiomyopathies who underwent CRT upgrades were retrospectively reviewed and divided into three groups: group 1 included CS patients taking corticosteroids before the CRT upgrade (n = 7), group 2, CS patients not taking corticosteroids before the CRT upgrade (n = 10), and group 3, non‐CS patients (n = 31). The echocardiographic response, heart failure hospitalizations, and cardiovascular deaths were evaluated.ResultsThe baseline characteristics during CRT upgrades exhibited no significant differences in the echocardiographic data between the three groups. After the CRT upgrade, responses regarding the ejection fraction (EF) and end‐systolic volume (ESV) were significantly lower in CS patients than non‐CS patients (ΔEF: group 1, 6.7% vs. group 2, 7.7% vs. group 3, 13.6%; p = .039, ΔESV: 3.0 ml vs. ‐12.7 ml vs. ‐37.2 ml; p = .008). The rate of an echocardiographic response was lowest in group 1 (29%). There were, however, no significant differences in the cumulative freedom from a composite outcome among the three groups (p = .19). No cardiovascular deaths occurred in group 1.ConclusionThe echocardiographic response to an upgrade to CRT and the long‐term prognosis in patients with CS should be carefully evaluated because of the complex etiologies and impact of immunosuppressive therapy.

Long-term monitoring of arrhythmias with cardiovascular implantable electronic devices in patients with cardiac sarcoidosis.

Risk stratification for sudden cardiac death (SCD) in cardiac sarcoidosis (CS) is challenging in patients without overt cardiac symptoms. The purpose of this study was to determine the incidence of ventricular arrhythmias (VAs) and mortality after long-term monitoring with a cardiovascular implantable electronic device (CIED) in CS patients identified after systematic screening of patients with extracardiac sarcoidosis (ECS). A retrospective study was performed in 547 predominantly Caucasian patients with ECS screened for cardiac involvement. If CS was diagnosed, risk stratification (high vs low risk) for SCD was performed by a multidisciplinary team. The primary endpoint was defined as sustained VA, appropriate implantable cardioverter-defibrillator (ICD) therapy, or cardiac death. In total, 105 patients were included (mean follow-up 33± 16 months). An ICD was implanted in 17 high-risk patients (16.2%), whereas 80 low-risk patients (76.1%) received an implantable loop recorder (ILR). Eight low-risk patients (7.6%) did not receive a device. The primary endpoint occurred in 4.8% (n = 5), with an overall annualized event rate of 1.7%. The annualized event rate was 9.8% in high-risk patients and 0.4% in low-risk patients. Nine low-risk patients received an ICD during follow-up, in 7 patients as a result of the ILR recordings. None of these patients required ICD therapy. InCS patients without overt cardiac symptoms at initial presentationthe annualized overall event rate was 1.7%; 10% in high-risk patients, but only 0.4% in low-risk patients. In low-risk patients long-term arrhythmia monitoring with an ILRenabled early detection of clinicallyimportant arrhythmias without showing impact on prognosis.

Inpatient characteristics, complications, and outcomes of patients with cardiac sarcoidosis: A study from the National Inpatient Sample

Although seen in ∼5% of sarcoidosis patients, cardiac sarcoidosis (CS) accounts for nearly 25% of disease-related deaths. This study aimed to describe characteristics and outcomes among CS patients. Patients diagnosed with CS in 2016–2017 in the US National Inpatient Sample Database were evaluated to study patient characteristics, reasons ascribed to admission, in-hospital outcomes, and complications. A total of 2420 patients (median age 56 years) were included in the analysis. Most admissions occurred due to ventricular tachycardia (12.8%), followed by myocarditis (9.9%) with a mean length of stay of 7 ± 7 days. The overall incidence of in-hospital mortality was 2.5%.

Multicenter Registry in the Japanese Cardiac Sarcoidosis Prognostic (J-CASP) Study: Baseline Characteristics and Validation of the Non-invasive Approach Using 18F-FDG PET.

Background: Recent advances in cardiac modalities contribute to the guidelines on the diagnosis of cardiac sarcoidosis (CS) updated by the Japanese Circulation Society. The multicenter registry, Japanese Cardiac Sarcoidosis Prognostic (J-CASP) study tried to reveal recent trends of diagnosis and outcomes in CS patients and to validate the non-invasive diagnostic approach, including cardiac 18F-fluorodeoxyglucose (FDG) study. Methods/results: Databases from 12 hospitals consisting of 231 CS patients (mean age, 64 years; female, 65%; LV ejection fraction, 47%) diagnosed by the guidelines with FDG positron emission tomography (PET) study were integrated to compile clinical information on the diagnostic criteria and outcomes. Cardiac 18F-FDG uptake and magnetic resonance imaging (CMR) was positive identically in the histology-proven and clinically-diagnosed groups. The histology-proven group more frequently had reduce LV ejection fraction, myocardial perfusion abnormality and low-grade electrocardiogram (ECG) abnormality (P=0.003 to 0.016) than did the clinical group. During a 45-month period, the histology-proven group more frequently underwent appropriate implantable cardioverter-defibrillator (ICD) treatment (14% versus 4%, P=0.013) and new electronic device implantation (30% versus 12%, P=0.007) than did clinical group, respectively. There, however, was no difference in all-cause or cardiac mortality or in new hospitalization due to heart failure progression between them. Conclusion: The J-CASP registry demonstrated the rationale and clinical efficacies of non-invasive approach using advanced cardiac imaging modalities in the diagnosis of CS even when histological data were available.

Controversies in the Treatment of Cardiac Sarcoidosis.

There are many challenging aspects of the management of cardiac sarcoidosis (CS) with corticosteroids and other immunosuppressive therapy (IST). First, it is not always clear who will benefit from therapy or when to initiate treatment. Secondly, there are no randomized controlled trials or large prospective studies to guide what medications to use, at what doses, and for how long. The European Respiratory Society (ERS) clinical practice guidelines on the treatment of sarcoidosis makes a strong recommendation for the use of immuno-suppressive therapy in CS patients with functional cardiac abnormalities, including heart blocks, dysrhythmias, or cardiomyopathy where patients are considered at-risk of adverse outcomes. Corticosteroids are the first line immunosuppressive therapy in CS however, early initiation of second-line steroid sparing medications has been advocated and there is data to suggest that concomitant initiation of therapy may be more beneficial. The use of anti-tumor necrosis factor (anti-TNF) agents (including infliximab and adalimumab) considered beneficial third-line anti-sarcoidosis treatment agents in other severe refractory manifestations of disease remains controversial.

Risk and predictors of mortality after implantable cardioverter-defibrillator implantation in patients with sarcoid cardiomyopathy

Implantable cardioverter-defibrillators (ICDs) are recommended for patients with cardiac sarcoidosis (CS) with an indication for pacing, prior ventricular arrhythmias, cardiac arrest, or left ventricular ejection fraction <35%, but data on outcomes are limited. Using data from the National Cardiovascular Data Registry ICD Registry between April 1, 2010 and December 31, 2015, we evaluated a propensity matched cohort of CS patients implanted with ICDs versus non-ischemic cardiomyopathies (NICM). We compared mortality using Kaplan-Meier survival curves and Cox proportional hazards models. We identified 1,638 patients with CS and 8,190 propensity matched patients with NICM. The rate of death at 1 and 2 years was similar in patients with CS and patients with NICM (5.2% vs 5.4%, P = 0.75 and 9.0% vs 9.3%, P = 0.72, respectively). After adjusting for other covariates, patients with CS had similar mortality at 2 years after ICD implantations compared with NICM patients (RR 1.03, 95% CI 0.87-1.23). Among patients with CS, multivariable logistic regression identified 6 factors significantly associated with increased 2-year mortality: presence of heart failure (HR 1.92, 95% CI 1.44-3.22), New York Heart Association (NYHA) Class III heart failure (HR 1.68, 95% CI 1.16-2.45), NYHA Class IV heart failure (HR 3.08, 95% CI 1.49-6.39), atrial fibrillation/flutter (HR 1.66, 95% CI 1.17-2.35), chronic lung disease (HR 1.64, 95% CI 1.17-2.29), creatinine >2.0 mg/dL (HR 4.07, 95% CI 2.63-6.30), and paced rhythm (HR 2.66, 95% CI 1.07-6.59). Mortality following ICD implantation was similar in CS patients compared with propensity matched NICM patients. Presence of heart failure, NYHA class, atrial fibrillation/flutter, chronic lung disease, renal dysfunction, and paced rhythm at time of implantation were all predictors of increased 2-year mortality among CS patients with ICDs.

Utility of electrophysiologic testing for sudden death risk stratification in cardiac sarcoidosis patients with mildly impaired left ventricular function

BackgroundVentricular arrhythmias (VA) account for at least 25% of deaths caused by cardiac sarcoidosis (CS) and may arise in patients with mildly impaired LVEF (>35%). ObjectiveIn the current study, we examine whether EP study may be used for sudden death risk stratification in CS patients who have mildly impaired LVEF and a diagnosis of highly probable or probable CS according to the World Association of Sarcoidosis and Other Granulomatous Diseases Sarcoidosis Organ Assessment Instrument (WASOGI). MethodsAll patients: (1) exhibited a diagnosis of highly probable or probable CS according to the WASOGI, (2) exhibited cardiac MRI findings consistent with CS, (3) exhibited LVEF >45% and (4) underwent EP study. Device interrogations, transmissions and medical records were reviewed for all patients. ResultsWe identified 46 CS patients with mildly impaired LVEF. VA were induced in 11 patients and 10/11 patients underwent ICD placement. Thirty-five patients had no VA and 24/35 patients underwent placement of an ILR. During the follow-up period, the VA event rate was 6.5%. The negative and positive predictive values of the EP study for the development of VA were 100% and 27.2%, respectively. ConclusionsIn CS patients with mildly impaired LVEF and a diagnosis of highly probable or probable CS, a negative EP study was highly predictive of the absence of VA. The successful execution of future prospective studies is contingent upon enrollment of phenotypically homogenous cardiac sarcoidosis patients.

The role of electrophysiology study in risk stratification of cardiac sarcoidosis patients: Meta-analyses and systemic review

BackgroundThe utility of an electrophysiologic study (EPS) in the risk stratification of cardiac sarcoidosis (CS) patients is not clear. We conducted a systemic review and meta-analysis to evaluate the utility of EPS in the risk stratification of CS patients. MethodsWe searched PubMed, Embase, and Scopus databases from their inception to 12/4/2020 with search terms “Cardiac sarcoidosis” And “Electrophysiological studies OR ablation”. The first and second authors reviewed all the studies. We extracted the data of positive and negative EPS, and outcomes defined as ventricular arrhythmias, implantable cardioverter defibrillator therapy, death, left ventricular assist device placement, or heart transplantation. Risk of bias assessment was done by the Quality Assessment of Diagnostic Accuracy Studies-2 tool. Subgroup analysis of patients with left ventricular ejection fraction (LVEF) >35%, and probable CS, no prior ventricular tachycardia (VT) and LVEF >35% were performed. ResultsWe found 544 articles after removing duplicates. A total of 52 full articles were reviewed, and eight studies were included in the meta-analysis. The pooled sensitivity and specificity (95% confidence interval) of EPS in predicting clinical outcomes were 0.70 (0.51–0.85) and 0.93 (0.85–0.97), respectively. Subgroup analysis of patients with LVEF >35% resulted in pooled sensitivity of 0.63 (0.29–0.88) and pooled specificity of 0.97 (0.92–0.99), and subgroup analysis of patients with probable CS, no prior VT, and LVEF >35% resulted in pooled sensitivity of 0.71 (0.33–0.93) and pooled specificity of 0.96 (0.88–0.99) in predicting adverse clinical outcomes. ConclusionsEPS is an effective risk stratification tool in patients with CS across all subgroups with high sensitivity and specificity.

Prognosis and Outcomes of Clinically Diagnosed Cardiac Sarcoidosis Without Positive Endomyocardial Biopsy Findings.

Diagnosis of cardiac sarcoidosis (CS) is sometimes difficult due to a low positive rate of epithelioid granulomas by endomyocardial biopsy (EMB). Accordingly, Japanese guidelines can allow the CS diagnosis using clinical data alone without EMB results (clinical CS) since 2006. However, little is known about prognosis and outcome of clinical CS. Purpose of this study was to analyze the prognosis, outcomes, and response to corticosteroid of clinical CS using large-scale cohort survey. Overall, 422 CS patients (mean age 60 ± 13 years, 68% female, median follow-up period of 5 years), including 345 clinical CS and 77 EMB-positive patients, histologically diagnosed CS (histological CS) by Japanese guidelines, were enrolled and examined. Clinical profile (age, sex, initial cardiac arrhythmias, and abnormal uptake of gallium-67 scintigraphy or 18F-fluorodeoxyglucose positron emission tomography in heart) was similar in both groups. Although clinical CS had better prognosis (P = 0.018) and outcome (all-cause death, appropriate defibrillator therapy, and heart transplantation; P = 0.008), multivariate Cox hazard analysis revealed that left ventricular ejection fraction (LVEF) and sustained ventricular tachycardia history were independently associated with outcome (P< 0.001 and P = 0.002, respectively), but not with the diagnosed CS category. Moreover, similar LVEF recovery after corticosteroid was observed in both groups with low LVEF (≤35%) at the 1-year follow-up period (P< 0.001). In clinical CS according to the Japanese guideline, prophylactic implantable-cardioverter-defibrillator and immunosuppressive therapy are important in patients with low LVEF or ventricular tachycardia history, similar to histological CS.

Fragmented QRS as a predictor of cardiac events in patients with cardiac sarcoidosis

Background: Multiple spikes within the QRS complex, known as fragmented QRS (fQRS), are associated with the occurrences of ventricular arrhythmic events (VAEs) in patients with Brugada syndrome and hypertrophic cardiomyopathy. However, the association between fQRS and occurrence of VAEs in patients with cardiac sarcoidosis (CS) has not been elucidated. Methods: We evaluated the associations between fQRS and cardiac events including VAEs [non-sustained ventricular tachycardia (NSVT), sustained ventricular tachycardia (VT), and ventricular fibrillation (VF)], hospitalization for heart failure, and all-cause death in 68 patients with CS (30 patients with fQRS vs. 38 patients without fQRS) over a 5-year period. Results: Cardiac events occurred in 22 patients with fQRS and 18 patients without fQRS (73% vs. 47%, p=0.009). Of the cardiac events that occurred in CS patients, VAEs occurred more frequently in patients with fQRS than in patients without fQRS (VAEs: 70% vs. 45%, p=0.017; NSVT: 70% vs. 45%, p=0.010; VT: 43% vs. 18%, p=0.011, and VF: 6.7% vs. 2.6%, p=0.34), whereas there was no significant difference in hospitalization for heart failure or all-cause death between patients with and those without fQRS (hospitalization for heart failure: 6.7% vs. 5.3%, p=0.75; all-cause death: 6.7% vs. 5.3%, p=0.64). Multivariate analysis showed that fQRS in the baseline electrocardiogram was independently associated with VAEs (hazard ratio: 2.21, 95% confidence interval: 1.15–4.25, p=0.017). Conclusion: fQRS is a predictor of VAEs in patients with CS.

Association of high serum soluble interleukin 2 receptor levels with risk of adverse events in patients with cardiac sarcoidosis

Abstract Background Sarcoidosis is a systemic granulomatous disease that affects multiple organs. Among these, the presence of cardiac involvement is recognised as a determinant of worse clinical outcomes. Soluble interleukin 2 receptor (sIL-2R) is a potentially useful biomarker in the diagnosis and evaluation of disease severity in patients with sarcoidosis. However, it remains to be seen whether sIL-2R is associated with the severity and activity of disease in patients with cardiac sarcoidosis (CS). Purpose The aims of this study were to investigate whether sIL-2R was associated with clinical outcomes and to clarify the relationship between sIL-2R levels and disease activity evaluated by 18F-fluorideoxyglucose in positron emission tomography/computed tomography (18F-FDG PET/CT) in patients with CS. Methods We examined 101 consecutive patients with CS who were admitted to our University HospitalbetweenMay 2003 and February 2020. Patients who had no data of serum sIL-2R levels before initiation of immunosuppressive therapy (n=18) were excluded. Ultimately, 83 patients were examined in this study. The primary outcome was a composite of advanced atrioventricular block (AVB), ventricular tachycardia or ventricular fibrillation (VT/VF), heart failure hospitalisation, and all-cause death. Inflammatory activity in the myocardium and lymph nodes were assessed by18F-FDG PET/CT. We used a published program to analyse the cardiac metabolic activity (CMA), and total lymph node glycolysis (TLyG), which are quantitative measures of FDG volume-intensity. Results During a median follow-up period of 2.96 (interquartile range 2.24–4.27) years, the primary outcome occurred in 24 patients (29%), including 1 advanced AVB, 13 VT/VF, 5 hospitalisations for heart failure, and 5 all-cause deaths. Kaplan-Meier analyses showed that the primary outcome occurred more frequently in patients with higher sIL-2R levels (&amp;gt;538 U/mL, the median) than in those with lower sIL-2R levels (Figure). A multivariable Cox regression analysis revealed that a higher sIL-2R level was independently associated with an increased subsequent risk of adverse events (hazard ratio 3.71, 95% confidence interval 1.63–8.44, p=0.002), even after adjustments for age, plasma B-type natriuretic peptide, estimated glomerular filtration rate, left ventricular ejection fraction, and late gadolinium enhancement, which are known to be strong determinants of worse clinical outcomes in patients with CS (Table). Furthermore, sIL-2R levels were significantly correlated with TLyG, the inflammatory activity in lymph nodes (r=0.346, p=0.003) but not with CMA, the inflammatory activity in myocardium (r=0.131, p=0.27). Conclusions Increased sIL-2R is associated with worse long-term clinical outcomes accompanied by increased systemic inflammatory activity in CS patients. These findings suggest the importance of assessing sIL-2R as a surrogate marker for further risk stratification in these patients. Funding Acknowledgement Type of funding sources: Public Institution(s). Main funding source(s): Japan Society for the Promotion of Science

Role of right ventricular free wall longitudinal strain in prediction outcome in patients with cardiac sarcoidosis

Abstract Introduction Right ventricular free wall longitudinal strain (RVFWLS) is a sensitive tool for right ventricular (RV) function assessment. Furthermore, it shows incremental prognostic role in various cardiac diseases. RV involvement is frequently observed along with left ventricular (LV) involvement in cardiac sarcoidosis (CS) patients, while its impact on outcome is unclear. Purpose The aim of this study is to investigate the association between RV dysfunction detected by RVFWLS and cardiovascular event in patients with CS. Methods We retrospectively evaluated 51 patients with CS who were treated with prednisone from 2012 through 2020. Diagnosis of CS was made according to the Japanese Circulation Society diagnostic criteria. We evaluated RVFWLS at baseline using vender-independent software. We considered major adverse cardiovascular event (MACE: ventricular arrhythmia, heart failure hospitalization) to be the primary outcome. Results Mean age of the study population was 63±11 years, and 61% were female. At baseline, 25 patients (49%) had reduced left ventricular (LV) ejection fraction (EF) (&amp;lt;50%) and 18 patients (35%) had impaired RVFWLS (&amp;lt;17%). Patients with impaired RVFWLS showed lower LVEF% (42±12% vs. 53±13%, P=0.005) and larger LV end-systolic volume index (54±33 vs. 37±23ml/m2, P=0.04) compared with those with preserved RVFWLS. Impaired RVFWLS patients also showed trend towards higher prevalence of basal interventricular thinning (50 vs. 28%, P=0.12). During a median follow-up of 548 days, eleven patients had MACE. In multivariable Cox-proportional hazards model analysis, RVFWLS was independently associated with MACE (HR 1.28, 95% CI: 1.07–1.10, P=0.009). Kaplan-Meier survival curves showed worse event-free survival in patients with impaired RVFWLS (log-rank test, P=0.001). Conclusions In patients with CS, RVFWLS is an independent predictor for MACE. RVFWLS may be valuable in improving risk stratification in CS. Funding Acknowledgement Type of funding sources: None. Kaplan-Meier survival curves

Clinical phenotypes of cardiac sarcoidosis by latent class analysis

Abstract Background Sarcoidosis is a systemic granulomatous disease with cardiac involvement reported in 20–27% of patients [1]. Cardiac sarcoidosis (CS) can lead to atrial or ventricular arrhythmias, various conduction system disorders, heart failure or sudden cardiac death, depending on the location of myocardial involvement [2]. Previous studies have investigated the possible types of CS based on the distribution of myocardial involvement on imaging as well as the role of genetic factors [3,4]. However, there are no studies describing the clinical heterogeneity of CS patients. Purpose In order to determine if clinical clusters exist in CS, we carried out a latent class analysis (LCA) to explore potential phenotypes in a large sample of CS patients from the National Inpatient Sample (NIS). Methods We identified 848 patients with a diagnosis of CS from the NIS in 2016–2018. A LCA was performed based on comorbidities. Utilizing the Bayesian information criterion and Akaike's information criterion we divided our study population into 3 cohorts. We subsequently applied the LCA model for our study population to fit each patient into one of the 3 cohorts. Finally, we compared the clinical outcomes among the 3 groups. Results Following LCA, patients in cohort 3 were strongly associated with a cardiometabolic syndrome profile with the highest prevalence of congestive heart failure (CHF, 95.1%), chronic kidney disease (CKD, 69.7%), diabetes mellitus (68.9%), hyperlipidemia (52.5%) and obesity (45.1%). Patients in cohort 2 had an intermediate prevalence of cardiometabolic syndrome with a universal diagnosis of hypertension (100%) but with the lowest number of CHF (32.5%) patients and none with CKD. Finally, patients in cohort 1 had the least comorbidities in comparison to the other groups but there was a higher prevalence of CHF (71.7%). There was no significant difference in mortality among the 3 groups, but acute respiratory failure was the highest in cohort 3. However, ventricular arrhythmias were more prevalent in cohort 1 patients (Table). Conclusion We identified 3 different types of CS based on their clinical phenotype. The clinical outcomes varied among the cohorts with ventricular arrhythmias being the most prevalent in patients with the least cardiometabolic comorbidities. Funding Acknowledgement Type of funding sources: None.

Applicability of the AHA/ACC/HRS guideline for implantable cardioverter defibrillator implantation in Japanese patients with cardiac sarcoidosis

Abstract Background Sarcoidosis is a systemic granulomatous disease that affects multiple organs. Cardiac involvement is a key determinant of poor clinical outcomes in the patients with sarcoidosis, as it causes congestive heart failure, conduction abnormalities, ventricular tachycardia and fibrillation (VT/VF), and sudden cardiac death (SCD). Although implantable cardioverter defibrillators (ICDs) are used to prevent SCD from VT/VF in patients with cardiac sarcoidosis (CS), the generalizability of the AHA/ACC/HRS guidelines for the Japanese CS patients remains unclear. Purpose We aimed to assess, among Japanese patients with CS, the ICD recommendations from the 2017 AHA/ACC/HRS Guidelines for Management of Patients with Ventricular Arrhythmias and the Prevention of Sudden Cardiac Death. Methods We examined 188 consecutive patients with CS in two tertiary hospitals between 1979 and 2020. The primary outcome was defined as a composite outcome involving SCD or ventricular arrhythmic events. Ventricular arrhythmic events were defined as either emergency treatment for VF or sustained VT, which included appropriate ICD therapy. Results During a median follow-up period of 5.68 (IQR: 4.87–6.70) years, the primary outcome occurred in 44 patients (23%), which included 6 cases of SCD and 38 cases of VT/VF. ICD implant was indicated based on left ventricular ejection fraction (LVEF) of ≤35% (class I recommendation) in 62 patients, with an annualized event rate of 3.93%. A LVEF of &amp;gt;35% with a need for a permanent pacemaker (class IIa recommendation) was observed for 53 patients, with an annualized event rate of 2.54%. A LVEF of &amp;gt;35% with late gadolinium enhancement (LGE) during cardiovascular magnetic resonance (class IIa recommendation) was observed for 62 patients, with an annualized event rate of 2.38% (Figure A). Kaplan-Meier analyses revealed that patients with a class I recommendation for ICD implantation had a significant higher incidence of the primary outcome, compared to patients with a class IIa recommendation and patients with no indication for ICD implantation (P=0.03). However, there were no significant differences in the incidence of the primary outcome between patients with a LVEF of &amp;gt;35% and a need for a permanent pacemaker and patients with a class I recommendation (P=0.08) or patients with a LVEF of ≤35% (P=0.31). Moreover, there was no significant difference in the incidence of the primary outcome between patients with a LVEF of &amp;gt;35% and LGE on cardiovascular magnetic resonance and patients with a class I recommendation (P=0.054) or patients with a LVEF of ≤35% (P=0.22) (Figure B). Conclusions The American guideline recommendations for ICD implantation might be applicable to Japanese patients with CS. Implantation of an ICD may need to be considered in these patients if they require a permanent pacemaker or have LGE, regardless of LVEF. Funding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Japan Society for the Promotion of Science

MAGIC OF ADVANCED IMAGING AND IMMUNOTHERAPY IN CARDIAC SARCOIDOSIS

TOPIC: Cardiovascular Disease TYPE: Medical Student/Resident Case Reports INTRODUCTION: This case report emphasizes the role of advanced imaging and immunotherapy in the diagnosis and management of cardiac sarcoidosis (CS). CASE PRESENTATION: A 52-year-old healthy male presented with near-syncope for 5 days. He had a blood pressure of 164/67 mmHg and a heart rate of 43 bpm. Electrocardiogram revealed complete-heart-block (CHB) with a ventricular rate of 38/min. Troponin T and electrolytes were normal, and Lyme's serology was negative. Echocardiogram was normal. Cardiac magnetic resonance imaging (CMR) revealed late gadolinium enhancement (LGE) affecting the mid inferior segment at the right ventricle (RV) insertion site (Figure 1). A cardiac and whole-body 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) scan showed focal areas of increased FDG uptake in the LV involving mid and basal anteroseptal segments, mid inferoseptal segment, basal inferolateral, and basal inferior segments with normal perfusion (Figure 2). The scan also revealed hypermetabolic bilateral hilar and mediastinal lymphadenopathy. A diagnosis of CS was made. An Implantable-Cardioverter-defibrillator (ICD) was placed and the patient was discharged on 40mg of prednisone and 20mg of leflunomide. Within 4 months, he went from 100% RV pacing to 0%. Eventually, the corticosteroid was tapered off. At follow-up after 1.5 years, RV pacing remained 0% on Leflunomide 20mg. DISCUSSION: One should always suspect CS in young patients with high-grade AV block. During the workup of CHB (Figure 3), the 2017 Japanese Circulation Society Working Group Criteria for diagnosing CS was followed (1). The patient had 2 characteristic findings strongly suggestive of sarcoidosis: (a) hilar lymphadenopathy and (b) significant tracer accumulation in the myocardium and hilar lymph nodes on FDG-PET scan. He also met 2 major criteria strongly suggestive of CS: (a) LGE on CMR and (b) abnormal myocardial FDG uptake. These findings, per the criteria, establish the clinical diagnosis of CS. The mainstay of treatment for CS is corticosteroids +/- steroid-sparing agents to decrease intra-cardiac inflammation (1). CHB patients with CS have a high risk of ventricular arrhythmias, hence should receive ICD (2). The addition of antimetabolite adjuvants is more effective than corticosteroids alone (3). They may reduce the total time of glucocorticoid therapy and keep patients in remission. CONCLUSIONS: Clinical diagnosis of CS can be established with FDG-PET imaging and CMR. CS patients with advanced heart block should receive ICD. Corticosteroids are the mainstay of treatment. Immunotherapy is an effective adjunct that can help taper the glucocorticoids and keep patients in remission. Early introduction of these agents should be considered in these patients. REFERENCE #1: 1. Trivieri MG et al. Challenges in Cardiac and Pulmonary Sarcoidosis: JACC State-of-the-Art Review. J Am Coll Cardiol 2020;76:1878-1901 REFERENCE #2: 2. Nordenswan H-K et al. Outcome of Cardiac Sarcoidosis Presenting With High-Grade Atrioventricular Block. Circulation: Arrhythmia and Electrophysiology 2018;11:e006145 REFERENCE #3: 3. Nagai S, Yokomatsu et al. Treatment with methotrexate and low-dose corticosteroids in sarcoidosis patients with cardiac lesions. Intern Med 2014;53:427-33. DISCLOSURES: No relevant relationships by Roy Chung, source=Web Response No relevant relationships by Sachin Kumar, source=Web Response No relevant relationships by Raunak Nair, source=Web Response

Association of high serum soluble interleukin 2 receptor levels with risk of adverse events in cardiac sarcoidosis.

AimsAlthough soluble interleukin 2 receptor (sIL‐2R) is a potentially useful biomarker in the diagnosis and evaluation of disease severity in patients with sarcoidosis, its prognostic implication in patients with cardiac sarcoidosis (CS) is unclear. We sought to investigate whether sIL‐2R was associated with clinical outcomes and to clarify the relationship between sIL‐2R levels and disease activity in patients with CS.Methods and resultsWe examined 83 consecutive patients with CS in our hospital who had available serum sIL‐2R data between May 2003 and February 2020. The primary outcome was a composite of advanced atrioventricular block, ventricular tachycardia or ventricular fibrillation, heart failure hospitalization, and all‐cause death. Inflammatory activity in the myocardium and lymph nodes was assessed by 18F‐fluorideoxyglucose positron emission tomography/computed tomography. During a median follow‐up period of 2.96 (IQR 2.24–4.27) years, the primary outcome occurred in 24 patients (29%). Higher serum sIL‐2R levels (>538 U/mL, the median) were significantly related to increased incidence of primary outcome (P = 0.037). Multivariable Cox regression analysis showed that a higher sIL‐2R was independently associated with an increased subsequent risk of adverse events (HR 3.71, 95% CI 1.63–8.44, P = 0.002), even after adjustment for significant covariates. sIL‐2R levels were significantly correlated to inflammatory activity in lymph nodes (r = 0.346, P = 0.003) but not the myocardium (r = 0.131, P = 0.27).ConclusionsIncreased sIL‐2R is associated with worse long‐term clinical outcomes accompanied by increased systemic inflammatory activity in CS patients.

B-PO05-173 CARDIAC CT VERSUS CARDIAC PET IN RISK STRATIFICATION OF CARDIAC SARCOID PATIENTS UNDERGOING CATHETER ABLATION FOR RECURRENT VENTRICULAR ARRHYTHMIA

Patients with cardiac sarcoidosis (CS) are at increased risk of ventricular arrhythmias with modest reduction by catheter ablation. It is unclear whether recurrence risk is driven by inflammation, scar, or both in CS patients. Our aim was to assess the utility of cardiac computed tomography (CT) and cardiac positron emission tomography (PET) in predicting risk of subsequent ventricular arrhythmic events (VA) in patients undergoing catheter ablation. 19 consecutive patients with CS underwent catheter ablation at our institution between 2017 and 2021. The primary endpoint was VA at follow-up, defined as ventricular fibrillation, sustained ventricular tachycardia, sudden cardiac death, or device therapy. Mean age was 59+/-12 years; 21% were female; Mean LVEF was 42% +/-12%. 18 had pre-procedural PETs, 14 had pre-procedural CTs, and one CT was excluded for excess artifact. Overall 10/19 (53%) patients had VA. Among those with VA, 8/8 (100%) had +LIE and 8/9 (89%) had +FDG, as compared to those without VA, among which 3/5 (60%) had +LIE and 8/9 (89%) had +FDG (p < 0.01). For VA, sensitivity of -LIE was 100% (95% CI .60,1) versus 50% (95% CI 0.26,0.74) for -FDG. Among patients with +LIE, there was no significant difference in rate of VA based on presence or absence of FDG (p = 0.11). Among CS patients undergoing catheter ablation, presence of late iodine enhancement on CT may be a more sensitive predictor of recurrent VA risk than FDG uptake on PET. CT may be the preferred initial risk stratification tool in CS patients undergoing catheter ablation. Scar-mediated VA may be the primary driver of recurrent VA in CS patients after catheter ablation.Tabled 1Test Characteristics for Prediction of Recurrent Ventricular Arrhythmia after Catheter AblationSensitivitySpecificityPositive Predictive ValueNegative Predictive ValueLIE+100%40%73%100%FDG+50%50%89%11% Open table in a new tab

B-PO01-086 PHARMACOLOGICAL THERAPIES AND DEVICE IMPLANTATION IN CARDIAC SARCOIDOSIS

Cardiac sarcoidosis (CS) has been associated with atrioventricular block (AVB) and other dysrhythmias. To assess the rates of cardiac device implantation following the diagnosis of CS, and the influence of various pharmacologic therapies on AVB. Using a multicenter database (Explorys Inc, Cleveland, OH, USA), which consists of an aggregate of de-identified electronic health record data, a cohort of patients with the diagnosis of CS between 01/2015 and 12/2020 was identified. Subsequently, the rate of cardiac device implantation within up to five years following the diagnosis was analyzed. In patients who did not require device implantation upon initial diagnosis of CS, we assessed the impact of various pharmacological therapies on the rate of subsequent AVB. Of 37,000,320 subjects in the database, we identified 2200 CS patients. Following the diagnosis of CS, device implantation was largely performed within the first 7 days [730 defibrillators (33.2%); 320 pacemakers (14.6%)], with only minimal increase thereafter (Figure 1A). In patients who did not require device implantation upon initial diagnosis, the rates of subsequent AVB were significantly different among various pharmacological agents (P < 0.05, Figure 1B). Cardiac device implantation was common in patients with CS, especially within one week of the initial diagnosis, reflecting a common manifestation of dysrhythmias as an initial presentation. Methotrexate, mycophenolate, and biological therapies demonstrated a statistically significant favorable effect on the rate of subsequent AVB in patients who did not require devices upon initial presentation.