Background: Transthyretin amyloidosis is a multi-system disease that may manifest as cardiomyopathy (ATTR-CM) and/or polyneuropathy. Both disease manifestations are associated with autonomic dysfunction. However, the prevalence of autonomic dysfunction in ATTR-CM remains to be evaluated. Methods: Within the scope of a prospective ATTR-CM registry, the Composite Autonomic Symptom Score-31 (COMPASS-31) questionnaire was applied to consecutive patients between November 2022 and November 2024. Baseline characteristics are described, and associations of the COMPASS-31 score with markers of disease severity were assessed. Kaplan–Meier analysis was utilized to assess the COMPASS-31 score’s association with a combined endpoint of all-cause mortality and heart failure-related hospitalizations. Results: A total of 129 ATTR-CM patients [81.7 years (IQR: 77.4–84.3), 108 male (83.7%)] were included in the final study cohort. After stratification using the COMPASS-31 median [14 points, interquartile range (IQR): 6–29], statistically significant differences with regard to New York Heart Association (NYHA) stage and the Kansas City Cardiomyopathy Questionnaire (KCCQ) were observed. Furthermore, the COMPASS-31 score was moderately correlated with the KCCQ score in Spearman correlation analysis (r = −0.55, p < 0.001). The primary endpoint occurred in 16 patients (13 HF-hospitalizations/3 deaths) after 6.3 (IQR: 2.8–17.1) months. In Kaplan–Meier analysis, a COMPASS-31 score above the median of 14 was also associated with the primary endpoint of all-cause mortality and HF-related hospitalization (log-rank p = 0.047). Conclusions: Autonomic dysfunction is highly prevalent in ATTR-CM, affecting almost two-thirds of patients. As the presence of autonomic dysfunction is likely associated with more severely impaired quality of life, routine screening for this disease manifestation of transthyretin amyloidosis may be advisable.

Background/Objectives: Hereditary transthyretin amyloidosis (ATTRv) is a heterogeneous multisystem disease caused by pathogenic transthyretin gene (TTR) variants. Increased awareness and availability of disease-modifying therapies have resulted in increased diagnoses, even in previously nonendemic regions. The aim of this study was to update the nationwide Austrian ATTRv registry by characterizing the clinical, genetic, and regional distribution of TTR variants. Methods: This multicenter, observational analysis examined ATTRv cases diagnosed in Austria between 2014 and 2025. Individuals were included according to the presence of pathogenic or likely pathogenic variants or variants of uncertain significance (VUSs) in TTR. Results: In total, 100 individuals were identified, including symptomatic and asymptomatic carriers. Compared with our previously presented data, the number of genetically confirmed ATTRv cases has more than doubled. Twenty-three TTR variants were identified. The most frequent pathologic variants were p.His108Arg (26%), p.Ile127Phe (11%), and p.Thr69Ile (9%), while p.Val113Leu (9%) represented the most frequent VUS. Significant regional clustering of p.His108Arg was documented in Vienna and Lower Austria. Other findings included a rising number of p.Val142Ile carriers and phenotypically relevant VUSs in 20 patients. Conclusions: Our findings revealed an increasing detection rate of ATTRv in a nonendemic European region. These data underscore the importance of multidisciplinary evaluation, cascade testing, and long-term monitoring to improve early diagnosis and timely management in hereditary amyloidosis.

Background/Objectives: Patients with transthyretin amyloid cardiomyopathy (ATTR-CM) often experience significantly reduced functional capacity due to myocardial involvement. Cardiopulmonary exercise testing (CPET) is the gold standard to quantify functional capacity, and ^99mTc-DPD scintigraphy and SPECT/CT have proven to be highly effective tools for diagnostic and disease monitoring. We aimed to investigate the complementary role and correlation between both methods, focusing on their combined potential as a strong prognostic framework for monitoring disease progression and evaluating treatment efficacy. Methods: A total of 44 patients with diagnosed ATTR-CM, who underwent ^99mTc-DPD scintigraphy and SPECT/CT imaging as well as CPET, were included. All patients were divided into two groups based on the median DPD retention index (low DPD uptake: ≤5.0, n = 22; high DPD uptake: >5.0, n = 22). Results: The mean age was 78 years, with 82% of participants being male. Significant correlations were observed between peak VO₂ and DPD retention index (r = −0.355, p = 0.018) as well as between peak VO₂ at anaerobic threshold with DPD retention index (r = −0.391, p = 0.009). Interestingly, there was no strong correlation between VE/VCO₂ slope and the retention index. A strong association was identified between cardiac biomarkers and peak VO₂, specifically for NT-proBNP (r = −0.530, p < 0.001) and Troponin T (r = −0.431, p < 0.001). Conclusions: In ATTR-CM, significant correlations were observed between key CPET parameters and quantitative cardiac DPD uptake, which further reflects on disease severity and functional impairment. Our findings highlight the utility of integrating CPET and SPECT/CT for comprehensive patient assessment in ATTR-CM.

Variant transthyretin amyloidosis cardiomyopathy (ATTRv-CM) is a rare form of cardiac amyloidosis associated with many possible mutations in the transthyretin gene, presenting as various distinct clinical phenotypes. Among these, the His108Arg mutation is the most prevalent TTR variant in Austria. However, data describing its clinical phenotype are lacking. This study aims to describe the characteristics, clinical manifestations, and outcomes of patients with the His108Arg variant focusing on cardiac involvement, disease progression, response to therapy, and imaging findings. Methods: Patients were enrolled from a prospective cardiac amyloidosis registry. The baseline assessment included comprehensive echocardiography, cardiac magnetic resonance imaging, a biomarker analysis, and a clinical evaluation. Patients were followed longitudinally, with outcomes such as arrhythmias, heart failure hospitalizations, and response to disease-targeted therapies recorded. Results: Between March 2012 and June 2024, a total of 20 carriers of the His108Arg variant were identified, with 12 exhibiting clear cardiac involvement and 8 remaining asymptomatic. The median age at diagnosis was 62.3 years with significant heterogeneity in the clinical presentation. Patients with ATTRv-CM had a high prevalence of atrial and ventricular arrhythmias, a reduced left ventricular ejection fraction, and elevated cardiac biomarkers. The majority received specific disease-modifying therapies, with varying tolerance and responses. A longitudinal follow-up indicated frequent arrhythmic events, heart failure exacerbations, and three cases of heart transplantation, underscoring the need for stringent monitoring and individualized management strategies. Conclusions: This study represents a unique, comprehensive analysis of the His108Arg variant in ATTR-CM, highlighting its clinical heterogeneity and significant impact on cardiac function and clinical outcomes.

Background: Sub-clinical inflammation is considered a key mechanism in cardiovascular disease and myocardial remodeling. We therefore evaluated whether the neutrophil–lymphocyte ratio (NLR), a simple inflammatory marker derived from a routine full blood count, is associated with myocardial fibrosis. Methods: Consecutive patients from a cardiac magnetic resonance imaging (CMR) registry were included and stratified by the NLR tertile. The association of the NLR and the levels of C-reactive protein (CRP) with CMR-derived myocardial T1 time and the extracellular volume fraction (ECV) were assessed using linear regression analysis and compared using Z-scores. In addition, an association with outcome was tested utilizing the log-rank test. Results: 1152 patients (72.4 years, 53.1% male) constituted the final cohort. The median NLR was 3.11 [interquartile range (IQR): 2.145–4.67]. Tertiles were based on the cut-off values ≤ 2.5, >2.5 and <4.0, and ≥4.0. A higher NLR tertile was associated with lower biventricular ejection fraction, hypertrophy, and increased right ventricular volume. The myocardial native T1 time [tertile 1 vs. 3: 1010 ms (984–1038) vs. 1030 (1001–1059), p < 0.001] and ECV [tertile 1 vs. 3: 26.3% (24.2–28.6) vs. 28.1% (25.5–31.4), p < 0.001] also significantly differed between the NLR tertiles. The NLR’s and the CRP’s association with elevated myocardial T1 time and ECV were comparable; however, the proportion of variation in the target variables explained by either was generally low. Conclusions: In our CMR all-comer cohort, NLR and CRP were significantly associated with prolonged myocardial T1 times and increased ECV. However, only a modest variation observed in both parameters was explained by either variable.