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