Comparison of long-term outcomes in patients with cardiac sarcoidosis treated with different immunosuppressive drugs.

Am J Cardiovasc Dis 2024;14(6):342-354 www.AJCD.us /ISSN:2160-200X/AJCD0159756 Original Article Comparison of long-term outcomes in patients with cardiac sarcoidosis treated with different immunosuppressive drugs Leighton A Hope1, Timothy Chrusciel2, Bilal Abuhaiba3, Div Verma4, Ravi Nayak5, Mina M Benjamin4 Saint Louis University School of Medicine, St. Louis, MO, USA; 2Department of Health and Clinical Outcomes Research, Saint Louis University School of Medicine, St. Louis, MO, USA; 3Division of Critical Care Medicine, Cairo University Hospitals, Cairo, Egypt; 4Division of Cardiovascular Medicine, SSM-Saint Louis University Hospital, St. Louis, MO, USA; 5Division of Critical Care Medicine, SSM-Saint Louis University Hospital, St. Louis, MO, USA 1 Received August 12, 2024; Accepted December 6, 2024; Epub December 15, 2024; Published December 30, 2024 Abstract: Background: We compared long-term clinical outcomes between patients with cardiac sarcoidosis (CS) who received no treatment (NT), steroid treatment (ST), disease-modifying anti-rheumatic drugs (DMARDs), or tumor necrosis factor alpha inhibitors (TNF). Methods: Patients from SSM healthcare system’s data warehouse were identified using ICD codes. Inclusion criteria included at least 6 months of follow-up. Outcomes studied were heart failure (HF) admissions, ventricular tachyarrhythmias (VTA), and pacemaker/defibrillator placement. Statistical analysis included multivariate logistic regression and Kaplan-Meier curves. Results: We identified 198, 174, 66, and 19 patients in NT, ST, DMARDs, and TNF groups respectively. Mean age was 62.4, 60.2, 56, and 54.4 respectively. There was no significant difference in the rate of medical comorbidities including pulmonary sarcoidosis between the groups. Mean follow up was 92.3 months. Percent incidences of VTA were 17.5, 16.3, 12.5, and 5.6 (P 0.57) in the NT, ST, DMARDs and TNF groups respectively. DMARDs and TNF groups had a lower incidence of HF admission (43.9% and 36.8%) compared to NT and ST (59.1% and 59.2%). In the multivariate model, compared to NT group, the odds ratio for HF admission was 1.08 (CI: 0.70-1.65), 0.64 (0.36-1.14) and 0.45 (0.17-1.20) in the ST, DMARDs and TNF groups respectively. There was no significant difference in the rate of pacemaker/defibrillator placement between the groups. Conclusion: In this retrospective study from a large healthcare system, CS patients treated with DMARDs or TNF had a trend for lower incidence of HF admission than those on NT or ST. Keywords: Cardiac sarcoidosis, heart failure, ventricular tachyarrhythmias, disease-modifying anti-rheumatic drugs, tumor necrosis factor alpha inhibitors Introduction Sarcoidosis is a multi-system granulomatous disorder, primarily affecting the lungs, and cardiac sarcoidosis (CS) is a rare manifestation that typically presents as an infiltrative cardiomyopathy, either in isolation or as part of systemic sarcoidosis [1]. Autopsy studies and systematic evaluations using magnetic resonance imaging (MRI) suggest that cardiac involvement occurs up to 30% of patients with systemic disease [2]. Patients with symptomatic CS and coexisting pulmonary involvement experience worse survival than other patients with extracardiac sarcoidosis [3, 4]. The three main manifestations of CS are ventricular arrhythmias, atrioventricular block, and heart failure (HF) [5, 6]. In patients with CS, the cardiomyopathy can manifest as either dilated cardiomyopathy with reduced left ventricular ejection fraction (LVEF) or as restrictive cardiomyopathy with normal LVEF. A common cause of mortality in patients with CS is sudden cardiac death secondary to ventricular arrhythmias [7-11]. The extreme heterogeneity in disease activity and long-term outcomes presents significant challenges in disease management. The decision to initiate treatment must be carefully balanced against the potential side effects of immunomodulatory therapies. Expert consensus recommends immunosuppressive therapy https://doi.org/10.62347/TSPL4520 Comparison of outcomes of cardiac sarcoidosis immunosuppressive regimes for symptomatic patients with CS, including those with heart failure (HF) due to left ventricular systolic dysfunction, heart block, or ventricular arrhythmias, provided there is evidence of active myocardial inflammation, as indicated by FDG-PET or myocardial histology. Because of the low event rate in observational studies of asymptomatic patients, treatment is often individualized, considering the risks and benefits, the burden of cardiac inflammation, and the extent of extracardiac inflammation [12, 13]. The goal of immunosuppressive therapy in CS patients is to control the inflammatory response and mitigate cardiac damage. Glucocorticoids have traditionally been the first-line therapy for CS, but their long-term use is associated with several adverse effects including infections, diabetes, weight gain, and osteoporosis [14]. Although corticosteroids are considered the first-line treatment for CS, several studies have shown that corticosteroid monotherapy leads to higher rates of relapse and disease progression [15-18]. As a result, glucocorticoid-sparing agents are increasingly used, either in combination with or as an alternative to glucocorticoids. These agents include disease-modifying anti-rheumatic drugs (DMARDs), most commonly methotrexate, and tumor necrosis factoralpha inhibitors (TNF inhibitors). There is a paucity of data from randomized, placebo-controlled clinical trials specifically focused on CS. The addition of a glucocorticoid-sparing agent to glucocorticoid therapy has been shown to be helpful in minimizing glucocorticoid-related toxicities [14, 19, 20] and reducing disease activity, as measured by fluorodeoxyglucose (FDG) cardiac uptake [21-26]. Furthermore, long-term follow-up studies have reported a decreased risk of radiological relapse, improved LVEF, and reduced high-grade heart block or ventricular tachycardia, and sudden death [23]. However, the level of evidence to support different treatment approaches for CS is low, with multiple potential confounders and biases inherent in the available studies [27]. We aimed to compare the long-term clinical efficacy of the different immunosuppressive drug regimens in patients with CS from a large healthcare system database. Methods Data were obtained from Saint Louis UniversitySSM (SLU-SSM) healthcare system’s Virtual 343 Data Warehouse (VDW). SLU-SSM is a member site of the Health Care Systems Research Network (HCSRN) (www.hcsrn.org) and the VDW was created and is maintained per HCSRN specifications. The SSM healthcare system includes locations in Missouri, Illinois, Oklahoma, and Wisconsin. The VDW contains deidentified clinical data for over 5 million patients dating back to 2008. Because patients do not actively participate and all data is deidentified, all studies utilizing VDW data are approved as non-human subjects research by the Saint Louis University I (...truncated)