Cardiac sarcoidosis presenting with complex conduction abnormalities as the first manifestation of widespread systemic sarcoidosis: a case report.

Background: Sarcoidosis is a granulomatous multi-organ disease of unknown aetiology. Despite being relatively rare, cardiac sarcoidosis constitutes a very important manifestation of sarcoidosis, as its symptoms regularly precede or occur in isolation of more prevalent ones, and as it is the main driver of mortality in systemic sarcoidosis. Case summary: We present the case of a 37-year-old woman, in which clinically isolated cardiac sarcoidosis revealed widespread systemic sarcoidosis. Apart from constitutional symptoms and strong recurrent dizziness (i.e. near-syncopes), which persisted for multiple years already, our patient initially presented with complex conduction abnormalities, including a right bundle branch block, left anterior hemi-block, and atrioventricular block °1. Following inconclusive endomyocardial biopsies, performed due to detection of focal septal scarring on cardiac magnetic resonance imaging, an 18F-FDG-PET-CT, performed upon admission to our clinic, showed distinct hypermetabolic lesions indicative of active inflammation in various organs and raised suspicion of systemic sarcoidosis. Eventually, histopathological evidence of non-caseating granulomas in affected lymph nodes, extracted by bronchoscopy, confirmed the diagnosis of systemic sarcoidosis after reasonable exclusion of other granulomatous diseases. Immediate initiation of long-term immunosuppressive therapy led to almost complete remission, as monitored by consequential 18F-FDG-PET-CT scans. Discussion: Unexplained complex conduction abnormalities in young patients may be a sign of sarcoidosis, even in isolation of more prevalent symptoms. Correct interpretation and prompt initiation of a structured interdisciplinary diagnostic workup, including 18F-FDG-PET-CT as the imaging modality of choice, are essential to initiate specific treatment and obviate the major risk of mortality resulting from cardiac sarcoidosis.

Emerging therapies in transthyretin amyloidosis - a new wave of hope after years of stagnancy?

Transthyretin amyloidosis (ATTR) is a rare, yet underdiagnosed disease characterized by progressive impairment of neurologic and cardiac function due to deposition of misfolded transthyretin. Despite great efforts, such as the introduction of orthotopic liver transplant, the devastating prognosis for both variant and wild-type ATTR patients remained unchanged over the last decades, mainly due to a lack of specific therapies. Fortunately, recent years saw the introduction of promising targeted therapies, which aim to interfere with the deposition of misfolded transthyretin (TTR) at various stages of the cascade underlying ATTR progression. These include TTR tetramer stabilizers (tafamidis, diflunisal, epigallocatechin-3-gallate), TTR silencers (inotersen, patisiran) and fibril disruptors (monoclonal antibodies, doxycycline and tauroursodeoxycholic acid). In the context of this review we explain their mechanisms of action, analyse their efficacy on neurologic and cardiac function based on all clinical trials conducted to date and discuss their clinical applicability. Eventually suggestions for future clinical research into the field are provided.