Background: The pathophysiology of heart failure (HF) with preserved ejection fraction (HFpEF) is suggested to be influenced by inflammation. Leukocyte indices, including the neutrophil–lymphocyte ratio (NLR), the monocyte–lymphocyte ratio (MLR), and the pan-immune inflammation value (PIV), can be utilized as biomarkers of systemic inflammation. Their prognostic utility is yet to be fully understood. Methods: Between December 2010 and May 2023, patients presenting to a tertiary referral center for HFpEF were included into a prospective registry. The association of the NLR, MLR, and PIV with the composite endpoint of all-cause mortality and HF-related hospitalization was tested utilizing Cox regression analysis. Results: In total, 479 patients (median 74.3, interquartile range (IQR): 69.22–78.3 years, 27.8% male) were included. Patients were observed for 43 (IQR: 11–70) months, during which a total of 267 (55.7%) patients met the primary endpoint. In a univariate Cox regression analysis, an above-the-median NLR implied a hazard ratio (HR) of 1.76 (95%-confidence interval (CI): 1.38–2.24, p < 0.001), an MLR of 1.46 (95%-CI: 1.14–1.86, p = 0.003), and a PIV of 1.67, 95%-CI: 1.30–2.13, p < 0.001) for the composite endpoint. After adjustment in a step-wise model, the NLR (HR: 1.81, 95%-CI: 1.22–2.69, p = 0.003), the MLR (HR: 1.57, 95%-CI: 1.06–2.34, p = 0.026), and the PIV (HR: 1.64, 95%-CI: 1.10–2.46, p = 0.015) remained significantly associated with the combined endpoint. Conclusions: The NLR, the MLR, and the PIV are simple biomarkers independently associated with outcomes in patients with HFpEF.

Background: Hereditary transthyretin amyloidosis (ATTRv) is a progressive multisystem disease, and some patients continue to deteriorate despite disease-modifying therapy. Real-world data on sequential treatment and on eplontersen after prior gene-silencing therapy are scarce. Case Presentation: A 60-year-old man with a family history suggestive of amyloidosis presented in early 2017 with heart failure (NYHA class II–III), chronic diarrhoea and carpal tunnel syndrome. Multimodality imaging, grade 3 bone scintigraphy, exclusion of a monoclonal protein (negative immunofixation and a normal serum free light chain ratio) and genetic testing established ATTRv amyloidosis due to the p.Thr80Ala variant, and colonic and duodenal biopsies showed gastrointestinal amyloid deposits. Between 2017 and 2025 he was treated sequentially with tafamidis, patisiran and vutrisiran. Over this period the disease progressed clinically, with weight loss, worsening axonal polyneuropathy on nerve conduction studies, rising NT-proBNP (up to 3808 pg/mL) and a decline in six-minute walk distance. In July 2025, vutrisiran was replaced by eplontersen. During 15 months of follow-up, eplontersen was well tolerated and body weight increased from 54 to 57 kg. NT-proBNP fluctuated without a sustained further rise (3093 pg/mL at the switch and 3141 pg/mL at 15 months), and troponin T and renal function were unchanged, whereas diarrhoea persisted and the six-minute walk distance was 360 m. Conclusions: This case shows clinical progression of p.Thr80Ala ATTRv amyloidosis despite sequential stabiliser and small interfering RNA therapy, followed by clinical stabilisation after a switch to eplontersen. Without serum TTR measurements and in a single patient, these observations do not allow conclusions about treatment efficacy.