Prednisone vs methotrexate in treatment naïve cardiac sarcoidosis

Background: Side effects limit the long-term use of glucocorticoids in cardiac sarcoidosis (CS), and methotrexate has gained attention as steroid sparing agent although the supporting evidence is poor. This study compared prednisone monotherapy, methotrexate monotherapy or a combination of both, in the reduction of myocardial Fluorine-18 fluorodeoxyglucose (FDG) uptake and clinical stabilization of CS patients. Methods and results: In this retrospective cohort study, 61 newly diagnosed and treatment naïve CS patients commenced treatment with prednisone (N = 21), methotrexate (N = 30) or prednisone and methotrexate (N = 10) between January 2010 and December 2017. Primary outcome was metabolic response on FDG PET/CT and secondary outcomes were treatment patterns, major adverse cardiovascular events, left ventricular ejection fraction, biomarkers and side effects. At a median treatment duration of 6.2 [5.7-7.2] months, 71.4% of patients were FDG PET/CT responders, and the overall myocardial maximum standardized uptake value decreased from 6.9 [5.0-10.1] to 3.4 [2.1-4.7] (P < 0.001), with no significant differences between treatment groups. During 24 months of follow-up, 7 patients (33.3%; prednisone), 6 patients (20.0%; methotrexate) and 1 patient (10.0%; combination group) experienced at least one major adverse cardiovascular event (P = 0.292). Left ventricular ejection fraction was preserved in all treatment groups. Conclusions: Significant suppression of cardiac FDG uptake occurred in CS patients after 6 months of prednisone, methotrexate or combination therapy. There were no significant differences in clinical outcomes during follow-up. These results warrant further investigation of methotrexate treatment in CS patients

Pulmonary hypertension and cardiac involvement in sarcoidosis

Sarcoidosis is a multisystem inflammatory disease of unknown origin, characterized by the presence of non-caseating granulomas. Pulmonary hypertension (PH) is a known, but rare complication of sarcoidosis and is associated with increased morbidity and mortality. Cardiac involvement is another leading cause of death in sarcoidosis. This thesis evaluates the diagnosis, treatment and prognosis of both PH and cardiac involvement in sarcoidosis. Clinicians should be aware of the diverse underlying pathophysiological mechanisms of PH in sarcoidosis and subsequent prognosis and treatment options. As the treatment highly depends on the underlying cause, clinical phenotyping can be a first step towards personalised therapeutic decision-making. PH-specific therapies might benefit the individual patient, but there is no strong evidence for effectiveness in the whole population. Cardiac sarcoidosis (CS) is associated with heart failure, arrhythmias and sudden cardiac death, although the rate of adverse events during follow-up varies greatly between CS patients. Advanced cardiac imaging (CMR and FDG PET/CT) and multidisciplinary team evaluation are crucial for adequate diagnosis. The optimal medical therapy of CS is still not determined, but immunosuppressive treatment should be initiated in symptomatic patients and should be considered in patients with cardiac inflammation. Finally, risk stratification has to be performed in each CS patient to determine which patient benefits from cardiac implantable electronic devices. Risk stratification is the first step towards tailor made medicine in CS

Value of echocardiography using knowledge-based reconstruction in determining right ventricular volumes in pulmonary sarcoidosis: comparison with cardiac magnetic resonance imaging

Right ventricular (RV) dysfunction in sarcoidosis is associated with adverse outcomes. Assessment of RV function by conventional transthoracic echocardiography (TTE) is challenging due to the complex RV geometry. Knowledge-based reconstruction (KBR) combines TTE measurements with three-dimensional coordinates to determine RV volumes. The aim of this study was to investigate the accuracy of TTE-KBR compared to the gold standard cardiac magnetic resonance imaging (CMR) in determining RV dimensions in pulmonary sarcoidosis. Pulmonary sarcoidosis patients prospectively received same-day TTE and TTE-KBR. If performed, CMR within 90 days after TTE-KBR was used as reference standard. Outcome parameters included RV end-diastolic volume (RVEDV), end-systolic volume (RVESV), stroke volume (RVSV) and ejection fraction (RVEF). 281 patients underwent same day TTE and TTE-KBR. In total, 122 patients received a CMR within 90 days of TTE and were included. TTE-KBR measured RVEDV and RVESV showed strong correlation with CMR measurements (R = 0.73, R = 0.76), while RVSV and RVEF correlated weakly (R = 0.46, R = 0.46). Bland-Altman analyses (mean bias ± 95% limits of agreement), showed good agreement for RVEDV (ΔRVEDVKBR-CMR, 5.67 ± 55.4 mL), while RVESV, RVSV and RVEF showed poor agreement (ΔRVESVKBR-CMR, 21.6 ± 34.1 mL; ΔRVSVKBR-CMR, - 16.1 ± 42.9 mL; ΔRVEFKBR-CMR, - 12.9 ± 16.4%). The image quality and time between CMR and TTE-KBR showed no impact on intermodality differences and there was no sign of a possible learning curve. TTE-KBR is convenient and shows good agreement with CMR for RVEDV. However, there is poor agreement for RVESV, RVSV and RVEF. The use of TTE-KBR does not seem to provide additional value in the determination of RV dimensions in pulmonary sarcoidosis patients

Predictors of appropriate implantable cardiac defibrillator therapy in cardiac sarcoidosis

Background: Cardiac sarcoidosis (CS) is associated with an increased risk for sudden cardiac death. An implantable cardiac defibrillator (ICD) is recommended in a subgroup of CS patients. However, the recommendations for primary prevention differ between guidelines. The purpose of the study was to evaluate the efficacy and safety of ICDs in CS and to identify predictors of appropriate therapy. Methods: A retrospective cohort study was performed in CS patients with an ICD implantation between 2010 and 2019. Primary outcome was appropriate ICD therapy. Independent predictors were calculated using Cox proportional hazard analysis. Results: 105 patients were included. An ICD was implanted for primary prevention in 79%. During a median follow-up of 2.8 years, 34 patients (32.4%) received appropriate ICD therapy of whom 24 (22.9%) received an appropriate shock. Three patients (2.9%) received an inappropriate shock due to atrial fibrillation. Independent predictors of appropriate therapy included prior ventricular arrhythmias (hazard ratio [HR]: 10.5 [95% confidence interval (CI): 5.0–21.9]) and right ventricular late gadolinium enhancement (LGE) (HR: 3.6 [95% CI: 1.7–7.6]). Within the primary prevention group, right ventricular LGE (HR: 5.7 [95% CI: 1.6–20.7]) was the only independent predictor of appropriate therapy. Left ventricular ejection fraction did not differ between patients with and without appropriate therapy (44.4% vs. 45.6%, p =.70). Conclusion: In CS patients with an ICD, a high rate of appropriate therapy was observed and a low rate of inappropriate shocks. Prior ventricular arrhythmias and right ventricular LGE were independent predictors of appropriate therapy

Prednisone vs methotrexate in treatment naïve cardiac sarcoidosis

Background: Side effects limit the long-term use of glucocorticoids in cardiac sarcoidosis (CS), and methotrexate has gained attention as steroid sparing agent although the supporting evidence is poor. This study compared prednisone monotherapy, methotrexate monotherapy or a combination of both, in the reduction of myocardial Fluorine-18 fluorodeoxyglucose (FDG) uptake and clinical stabilization of CS patients. Methods and results: In this retrospective cohort study, 61 newly diagnosed and treatment naïve CS patients commenced treatment with prednisone (N = 21), methotrexate (N = 30) or prednisone and methotrexate (N = 10) between January 2010 and December 2017. Primary outcome was metabolic response on FDG PET/CT and secondary outcomes were treatment patterns, major adverse cardiovascular events, left ventricular ejection fraction, biomarkers and side effects. At a median treatment duration of 6.2 [5.7-7.2] months, 71.4% of patients were FDG PET/CT responders, and the overall myocardial maximum standardized uptake value decreased from 6.9 [5.0-10.1] to 3.4 [2.1-4.7] (P < 0.001), with no significant differences between treatment groups. During 24 months of follow-up, 7 patients (33.3%; prednisone), 6 patients (20.0%; methotrexate) and 1 patient (10.0%; combination group) experienced at least one major adverse cardiovascular event (P = 0.292). Left ventricular ejection fraction was preserved in all treatment groups. Conclusions: Significant suppression of cardiac FDG uptake occurred in CS patients after 6 months of prednisone, methotrexate or combination therapy. There were no significant differences in clinical outcomes during follow-up. These results warrant further investigation of methotrexate treatment in CS patients

Clinical Phenotypes of Sarcoidosis-Associated Pulmonary Hypertension

Background and objective: Pulmonary hypertension (PH) is a known complication of pulmonary sarcoidosis and its aetiology is unclear. Different pathophysiological mechanisms in sarcoidosis-associated pulmonary hypertension (SAPH) are known. Clinical phenotyping can aid clinicians in choosing the optimal treatment strategy. This study aimed to describe clinical phenotypes of SAPH and their characteristics. Methods: A retrospective cohort study was performed on all SAPH patients at a tertiary referral centre. All patients were extensively analysed and discussed case by case in a multidisciplinary expert team to determine the most likely pathophysiological mechanism of PH. Patients were then classified into conceptual clinical phenotypes. Results: Forty (40) patients with SAPH were identified between 2010 and 2019. Three (3) patients were classified as the postcapillary phenotype. Of the remaining 37 patients with precapillary PH, six were classified as ‘compression of pulmonary vasculature’, 29 as ‘parenchymal’, one as ‘suspected vasculopathy’, and one as ‘chronic pulmonary emboli’ phenotypes. Of the patients with compression of pulmonary vasculature, four showed compression by fibrotic disease and two by active sarcoidosis-based disease. Within the parenchymal phenotype, 20 patients (69%) showed pulmonary vascular resistance >3.0 Wood Units (WU) and had significantly lower diffusing capacity of the lung for carbon monoxide compared with the nine patients (31%) with pulmonary vascular resistance ≤3.0 WU. Conclusion: SAPH had multiple pathophysiological mechanisms and clinical phenotypes in this retrospective study. Further studies are necessary to examine how these phenotypes can affect appropriate treatment and prognosis

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

Background: Risk stratification for sudden cardiac death (SCD) in cardiac sarcoidosis (CS) is challenging in patients without overt cardiac symptoms. Objective: 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). Methods: 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. Results: 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. Conclusion: In CS patients without overt cardiac symptoms at initial presentation the 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 ILR enabled early detection of clinically important arrhythmias without showing impact on prognosis