Changes in the diagnostic trajectory of transthyretin cardiac amyloidosis over six years.

Awareness of transthyretin amyloid cardiomyopathy (ATTR-CM) has increased over the years due to diagnostic and therapeutic developments. Timely initiation of novel disease-modifying treatments improves both morbidity and mortality, which underlines the necessity for a prompt diagnosis. Nevertheless, early diagnosis of ATTR-CM remains challenging. This is a retrospective observational cohort study of patients diagnosed with ATTR-CM. Between 2016 and 2023, 87 patients were diagnosed with cardiac amyloidosis of which 65 (75%) patients with ATTR-CM and 22 (25%) patients with light chain amyloidosis. This study included 65 ATTR-CM patients (mean age 77 ± 7 years; 86% male) of whom 59 (91%) with wild-type ATTR-CM (ATTRwt) and six (9%) with variant ATTR-CM. We observed a surge in ATTR-CM diagnoses from 3 patients/year (2016-2020) to 16 patients/year (2021-2023), driven by ATTRwt. Nevertheless, the interval between the onset of heart failure symptoms and ATTR-CM diagnosis has not changed significantly (2016-2020 27.3 months [18.6-62.4]; 2021-2023 30.0 months [8.6-57.2]; p = 0.546), driven by time to referral. Red flags for ATTR-CM preceded diagnosis by several years: left ventricular hypertrophy (79%, 5.8 years [3.3-7.0]) and carpal tunnel syndrome (49%, 6.8 years [2.3-12.1]). Despite the presence of typical red flags, symptom-to-diagnosis duration has remained similar driven by time to referral. Improved recognition of red flags for ATTR-CM could reduce the time to diagnosis and improve overall recognition.

Acute heart failure and iron deficiency: a prospective, multicentre, observational study.

AIMS: The prevalence and the natural course of iron deficiency (ID) in acute heart failure (AHF) are still unclear. We investigated the prevalence of ID in unselected patients admitted with AHF on admission, at discharge and up to 3 months thereafter. METHODS AND RESULTS: In this prospective, multicentre, observational study, 742 patients admitted with AHF were enrolled. The main study outcome was the percentage of patients with ID (ferritin <100 µg/L = absolute ID or ferritin 100-299 µg/L and transferrin saturation <20% = functional ID) at admission (T0), after clinical stabilization prior to discharge (T1), and 10 ± 6 weeks after discharge (T2). At T0, ID was present in 71.8% of the patients (44.1% absolute and 27.7% functional ID). At T1 and T2, ID was present in 56.4% (32.4% absolute and 24% functional ID) and 50.3% (36.8% absolute and 13.5% functional ID), respectively. Absolute ID persisted from T0 to T2 in 66% of the patients, while functional ID resolved in 56% of the patients. Ferritin (median [interquartile range] 124 µg/L [56-247] to 150 µg/L [73-277]), transferrin saturation (15% [10-20] to 18% [12-27]), and iron levels (9 µmol/L [6-13] to 11 µmol/L [8-16]) increased significantly (all P < 0.001) from T0 to T1. Transferrin saturation (to 21% [15-29]) and iron levels (to 13 µmol/L [9-17]) also increased significantly (both P < 0.01) from T1 to T2 without iron supplementation. CONCLUSIONS: Iron deficiency is highly prevalent in patients with AHF, but resolves during treatment in some patients, even without iron supplementation. Absolute ID is more likely to persist over time, whereas functional ID often resolves during treatment of AHF, representing probably a reduced iron availability rather than a true deficiency.

Iron deficiency impacts prognosis but less exercise capacity in heart failure with preserved ejection fraction.

AIMS: Whether and how iron deficiency (ID) impacts patients with heart failure (HF) with preserved ejection fraction (HFpEF) remain unclear. The aim of our study was to investigate the impact of ID on functional status, exercise capacity, and prognosis in HFpEF. METHODS AND RESULTS: The study population consisted of 300 HFpEF patients. ID was defined as serum ferritin <100 µg/L or 100-300 µg/L and transferrin-saturation <20%. Baseline functional status, quality of life (HADS score and EQ 5D index), 6 min walking test, echocardiography, and outcome (all-cause mortality and combined all cause-mortality and HF hospitalization) were evaluated. ID was found in 159 (53%) patients. Patients with ID had a worse prognosis with a higher combined endpoint of all-cause mortality and HF hospitalization after 4 years of follow-up (log rank = 0.008). Pulmonary hypertension, depression, and thyroid disease were more prevalent in the ID group. Multivariable analysis showed that ID was independently associated with body mass index (P = 0.003), pulmonary hypertension (P = 0.008), and thyroid disease (P = 0.01). Although patients with ID had a lower exercise capacity compared with patients without ID (393 m [294-455] vs. 344 m [260-441], P = 0.008), there was no significant correlation after multivariable correction for age, BMI, NT-proBNP, DM, and depression. CONCLUSIONS: Heart failure with preserved ejection fraction patients with ID have a worse prognosis and impaired exercise capacity compared with those without ID. However, although a trend was observed, after multivariable correction ID was no longer significantly associated with a reduced exercise capacity. This reflects that impaired exercise capacity in HFpEF is complex and seems multifactorial. Interestingly, pulmonary hypertension was an independent predictor of both ID and exercise capacity.