Complex management of ATTRv amyloidosis (Glu89Gln) amid hemodynamic instability and heart failure: A case report

Background ATTRv with the NM_000371.4:c.325G>C, p.Glu109Gln (legacy p.Glu89Gln) mutation, reported in endemic clusters in southern Italy and Bulgaria, is characterized by an aggressive mixed cardio-neurological phenotype. The disease typically manifests around the age of 50. The burden of altered hemodynamics and orthostatic intolerance superimposed on the restrictive cardiomyopathy makes advanced heart failure management a significant clinical challenge. Case summary We present the case of a 59-year-old male with ATTRv amyloidosis carrying the Glu89Gln mutation, alongside type 2 diabetes and macroalbuminuric nephropathy. Despite a genetic diagnosis in 2006 following carpal tunnel syndrome and mild orthostatic hypotension, cardiac involvement was only formally recognized in 2022. Following a period of stability on tafamidis 61 mg/day, he developed weight gain, refractory right-sided acute heart failure and cardio-renal syndrome in 2026. Severe diuretic resistance and hypotension (<95 mmHg) occurred. A large-volume paracentesis (>10 L) was performed and plausibly contributed to the marked improvement of renal function and the restoration of diuretic responsiveness. As a net result of the overall strategy, a 32-kg net weight reduction was achieved over 13 days, leading to discharge in NYHA class II and improvement of Six-Minute Walk Test (6MWT) distance. Discussion Managing congestion in patients with restrictive physiology and susceptibility to hypotension requires multidisciplinary approaches, including unconventional ones, such as evacuative paracentesis. Furthermore, adapting disease-modifying therapies requires careful shared decision-making, balancing the potential benefits of gene silencers with real-world patient preferences and clinical stability.