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.

Autonomic dysfunction is well recognized in hereditary transthyretin amyloidosis (ATTRv), but it has not been systematically studied in wild-type transthyretin amyloidosis (ATTRwt). Because ATTRwt primarily presents with cardiomyopathy, autonomic symptoms may mimic heart failure and lead to inappropriate treatment. Here we aimed to investigate the presence and extent of autonomic dysfunction in ATTRwt. In ATTRwt patients and controls, we performed an extensive autonomic examination, including standardized questionnaires, passive and active orthostatic challenges, Valsalva maneuver, deep breathing and sudomotor assessment. 20 ATTRwt patients and 20 controls were included. Composite Autonomic Symptom Score 31-scores were similar between the groups. Orthostatic challenges revealed impaired blood pressure (BP) and heart rate regulation in ATTRwt compared to controls (for passive orthostatic challenge: HR p = 0.001, systolic BP p = 0.010) and diastolic BP p = 0.006; for active orthostatic challenge: HR p = 0.001, systolic BP p = 0.002, diastolic BP p = 0.002). A lack of late phase 2 BP overshoot during Valsalva maneuver was observed in ATTRwt and Valsalva Ratio was pathological in 83

Isolated cardiac sarcoidosis (iCS), defined by granulomatous inflammation limited to the myocardium, represents the most diagnostically challenging and prognostically adverse form of sarcoidosis. As it is fundamentally a diagnosis of exclusion, iCS diagnosis relies on the absence of extracardiac sarcoid and the integration of multimodality imaging, endomyocardial biopsy, and molecular testing, each with inherent limitations. Cardiac magnetic resonance and positron emission tomography provide complementary assessment of inflammation, fibrosis, and ventricular function, enhancing diagnostic confidence. Electroanatomic mapping-guided biopsy may improve histologic yield, whereas genetic testing helps exclude phenocopies such as arrhythmogenic, hypertrophic, or dilated cardiomyopathies. Circulating biomarkers remain non-specific but may complement imaging-based algorithms. Future research should focus on harmonized imaging protocols, non-FDG radiotracers, and molecular tissue profiling to refine activity assessment and guide therapy. Multimodal, probability-based frameworks represent the most promising approach for earlier, more accurate diagnosis and risk stratification in iCS.

Wild-type transthyretin amyloidosis (ATTRwt) is a progressive disease marked by extracellular transthyretin amyloid deposition, predominantly causing cardiomyopathy. Neurological manifestations are known in hereditary ATTR but remain comparatively understudied in ATTRwt. Patients with ATTRwt cardiomyopathy were prospectively evaluated at baseline and after 1 year, alongside healthy controls. Neurological assessment included Neuropathy Impairment Score Lower Limb (NIS-LL), nerve conduction studies, quantitative sensory testing (QST), serum neurofilament light chain (sNfL), and intra-epidermal nerve fiber density (IENFD) from skin biopsies. Symptoms and fatigue were assessed using Norfolk-QoL-DN and Chalder Fatigue scale. Twenty-three patients were included and compared to controls. Pathological IENFD occurred in 47.8

INTRODUCTION:Molecular genetic testing is increasingly offered to patients with dilated cardiomyopathy (DCM). The diagnosis of an inherited cardiomyopathy has major implications for medical care of patients and relatives. We report the results of a genotype-phenotype analysis of DCM investigated in Austria. METHODS:Overall, 194 patients with DCM underwent genetic testing over a period of 6 years. We analyzed the clinical and genetic characteristics of 105 DCM patients who showed a genetic variant and compared the genetic findings and outcome measures of patients with myocardial inflammation on endomyocardial biopsy and those without. RESULTS:In 51.4% (54/105) patients, at least one likely pathogenic or pathogenic genetic variant (LP/P) was detected. Fifty one of 105 patients (48.6%) showed only variants of unknown significance (VUSs). Most LP/P variants (34.3%) were detected in the TTN gene. Clinical characteristics of the most prevalent genetic subgroups (TTN, LMNA, MYH7, MYH6, DMD, SCN5A) were not significantly different. DCM patients with inflammation had significantly higher frequency of memory of infection, left bundle branch block, mitral valve insufficiency but normal CK-MB levels. We added a case report where two family members initially were considered to have an inflammatory cardiomyopathy before a pathogenic variant in LMNA was found. CONCLUSION:Cardiac features of DCM were not predictive of a specific genetic subgroup. We recommend applying multigene panels extensively since a large proportion of patients without a family history or with evidence of myocardial inflammation showed a genetic predisposition for DCM. However, the large number of VUS remains a challenge.

In this multicenter study we investigated whether echocardiography-derived left ventricular global longitudinal strain (LV GLS), an indicator of myocardial fibrosis, independently predicts a positive genotype in hypertrophic cardiomyopathy (HCM). We performed a cross-sectional analysis including HCM patients with genetic testing results and echocardiographic data from two Austrian HCM registries. Echocardiographic parameters were measured in post-processing analysis by a blinded investigator. Among 125 patients with HCM, a positive genotype was present in 39%. Worse LV GLS was associated with a positive genotype in univariate analysis (Odds Ratio [OR] 95% CI 1.141, 1.018-1.279, p = 0.023). In multivariate regression analysis adjusted for genotype predictors (age at diagnosis < 45 years, arterial hypertension, positive family history of HCM, maximal to posterior wall thickness [MWTH: PWTH], reverse curve septal phenotype), the reverse curve septal phenotype remained as a single independent predictor of genotype-positive HCM (OR 6.948, 2.342-20.614, p < 0.001). Adding LV GLS to established Toronto and Mayo genotype prediction scores did not improve their performance. To conclude, worse LV GLS was not independently associated with genotype-positive HCM and did not improve the diagnostic yield of genetic testing in HCM in a multivariate model. Our study highlights the reverse curve septal phenotype as the strongest genotype predictor in HCM.

Iron deficiency (ID) is a common comorbidity in heart failure (HF), affecting 55% of chronic and up to 80% of acute HF patients, regardless of ejection fraction (EF). An ID is associated with reduced quality of life, impaired exercise capacity (VO2 peak), higher hospitalization rate and lower survival rate. It is also an independent predictor of HF outcomes. This consensus statement critically reviews the diagnostic criteria for ID in HF and provides recommendations for their use. The efficacy and safety of intravenous iron supplements, including ferric carboxymaltose (FCM) and ferric derisomaltose (FDI), are analyzed highlighting the indications and potential adverse effects. Key clinical trials and guideline recommendations are summarized. In summary, the document addresses the diagnostics, treatment and monitoring of ID in HF.

Abstract Aims Iron is essential to maintain cellular energy metabolism in the myocardium. Impaired cellular iron availability negatively affects myocardial physiology and can aggravate heart failure (HF). Iron deficiency (ID) is frequently found in patients with acute and chronic HF (AHF, CHF) and associated with clinical outcome. The aim of this analysis was to assess the true ID prevalence in HF patients on the basis of different ID definitions. Methods We performed a retrospective analysis of 329 AHF and 613 CHF patients, recruited between 02/2021 and 05/2022 at the Innsbruck Medical University (47%/32% female, median age 81/64 years). ID was defined according to a general definition, gastroenterology and cardiology guidelines as ferritin <30 or <45 ng/mL or <100/ng/mL (absolute ID), ferritin 30–100 or 45–150 or 100–299 ng/mL plus TSAT <20% (combined ID), and ferritin >100 or >150 or ≥300 ng/mL plus TSAT <20% (functional ID). Results ID prevalence was significantly higher in AHF compared with CHF patients: general definition (74.8% vs. 32.6%, P < 0.001), gastroenterology guidelines (75.7% vs. 34.7%, P < 0.001), cardiology guidelines (79.9% vs. 47.3%, P < 0.001). We found distinctive differences in prevalence of ID types between the three definitions. Absolute ID prevalence was highest when applying cardiology compared with gastroenterology guidelines and general definition (AHF: 44.7% vs. 20.4% vs. 7.0%; CHF: 34.1% vs. 13.4% vs. 7.2%), while frequency of combined ID was almost equally distributed. Functional ID prevalence was highest when applying general definition compared with gastroenterology and cardiology guidelines (AHF: 34.7% vs. 23.4% vs. 11.6%; CHF: 13.1% vs. 9.0% vs. 3.4%). Out of 494 patients classified as having absolute or combined ID according to the cardiology guidelines, only 252 patients received the same classification while 107 and 135 patients were classified having no and functional ID when applying the general definition. Conclusions We show that ID prevalence is higher in AHF versus CHF patients in a continuous cohort of HF patients managed at the same institution over the same period of time. There were distinctive differences in detection of ID and the type of ID when applying several recommended definitions thus affecting sensitivity and specificity for absolute and functional ID detection. This may result in exclusion of patients, which may benefit from iron supplementation and inclusion of those who may not respond or even anticipate site effects. Our study calls for the urgent need of prospective trials for redefinition of ID and identification of biomarkers associated with therapeutic response to optimize patient outcomes.

Hypertrophic cardiomyopathy (HCM) is the most common inherited heart disease that is characterized by left ventricular hypertrophy unexplained by secondary causes. Based on international epidemiological data, around 20,000–40,000 patients are expected to be affected in Austria. Due to the wide variety of clinical and morphological manifestations the diagnosis can be difficult and the disease therefore often goes unrecognized. HCM is associated with a substantial reduction in quality of life and can lead to sudden cardiac death, especially in younger patients. Early and correct diagnosis, including genetic testing, is essential for comprehensive counselling of patients and their families and for effective treatment. The latter is especially true as an effective treatment of outflow tract obstruction has recently become available in the form of a first in class cardiac myosin ATPase inhibitor, as a noninvasive alternative to established septal reduction therapies. The aim of this Austrian consensus statement is to summarize the recommendations of international guidelines with respect to the genetic background, pathophysiology, diagnostics and management in the context of the Austrian healthcare system and resources, and to present them in easy to understand algorithms.

Objective This study aimed to assess the cost-effectiveness of the telemedically assisted post-discharge management program (DMP) HerzMobil Tirol (HMT) for heart failure (HF) patients in clinical practice in Austria. Methods We conducted a cost-effectiveness analysis along a retrospective cohort study (2016–2019) of HMT with a propensity score matched cohort of 251 individuals in the HMT and 257 in the usual care (UC) group and a 1-year follow-up. We calculated the effectiveness (hospital-free survival, hospital-free life-years gained, and number of avoided rehospitalizations), costs (HMT, rehospitalizations), and the incremental cost-effectiveness ratio (ICER). We performed a nonparametric sensitivity analysis with bootstrap sampling and sensitivity analyses on costs of HF rehospitalizations and on costs per disease-related diagnosis (DRG) score for rehospitalizations. Results Base-case analysis showed that HMT resulted in an average of 42 additional hospital-free days, 40 additional days alive, and 0.12 avoided hospitalizations per patient-year compared with UC during follow-up. The average HMT costs were EUR 1916 per person. Mean rehospitalization costs were EUR 5551 in HMT and EUR 6943 in UC. The ICER of HMT compared to UC was EUR 4773 per life-year gained outside the hospital. In a sensitivity analysis, HMT was cost-saving when “non-HF related costs” related to the DMP were replaced with average costs. Conclusions The economic evaluation along the cohort study showed that the HerzMobil Tirol is very cost-effective compared to UC and cost-saving in a sensitivity analysis correcting for “non-HF related costs.” These findings promote a widespread adoption of telemedicine-assisted DMP for HF. Graphical abstract

Transcatheter edge-to-edge repair (TEER) is a less invasive alternative to mitral valve surgery. In patients with advanced heart failure (HF), TEER can improve pulmonary hypertension (PH) and decelerate the progression of HF. TEER could be considered as a possible bridging strategy before orthotopic heart transplantation (OHT) in suitable patients. We report our experience in patients with advanced HF and severe functional mitral regurgitation (FMR) who underwent TEER prior to OHT. In this retrospective single-center study, we evaluated the periprocedural characteristics and clinical and hemodynamic outcomes of 14 patients with advanced HF on guideline-directed medical therapy and severe FMR who underwent TEER prior to OHT. In 6 patients who were not eligible for transplantation because of PH, TEER was performed as bridge-to-candidacy (BTC) strategy, in 8 unstable patients on the waiting list as bridge-to-transplant (BTT) strategy. Severity of FMR was reduced by 2 degrees from 4 (3-4) to 2 (1.25-2.25) (p < 0.001), NYHA class from 3 (2-3) to 2 (1.75-2.13) (p = 0.003) and NT-proBNP from 4689 (2841-7932) ng/L to 2973 (1694-4812) ng/L (p = 0.008). Significant reduction in PH was observed in the BTC cohort (mean PAP from 50 (39-53) to 26 (23-33) (p = 0.027) and PCWP from to 34 (29-40) to 13.5 (11-21) mmHg (p = 0.027). 13 patients underwent successful OHT, 1 patient of the BTT cohort died of sepsis shortly after HTX listing. In conclusion patients with advanced HF and severe FMR who are considered for OHT, TEER appears suitable both as a BTC strategy in patients with PH and as a BTT strategy in unstable patients on the waiting list.

Abstract Background Elevated levels of N-terminal prohormone of brain natriuretic peptide (NT-proBNP) reflect cardiac status in heart failure patients and are independently associated with mortality and adverse cardiovascular outcomes in elective patients undergoing non-cardiac surgery. However, there is scarce evidence about the association between NT-proBNP and outcome after cardiac surgery in large patient populations. Purpose The aim of this study was to analyze the association of preoperative NT-pro-BNP levels with 30-day and five-year mortality after cardiac surgery. Methods A consecutive cohort of 6938 patients undergoing cardiac surgery was analyzed retrospectively. The relationship between preoperative NT-proBNP and 30-day and five-year mortality adjusted for EuroSCORE II was explored using a Cox proportional hazards model. The dynamics of preoperative NT-proBNP were analyzed by comparing the values at the time of diagnosis or assignment to surgery with the values on the day before surgery (n= 4739). Results were validated in an external cohort from the SWEDEHEART registry (n=3415). Results Median preoperative NT-proBNP was 552 ng/l. Death within 30 days occurred in 2.1% of the patients. High preoperative NT-proBNP levels were associated with a higher 30-dayand 5-yearmortality. Preoperative NT-proBNP thresholds to identify patients at high-risk (>4000 ng/l), intermediate-risk (2000-4000 ng/l) and low-risk (<2000 ng/l) for 30-day mortality were determined. Patients in the intermediate or high-risk category had a higher risk for prolonged ICU stay (OR 2.52), ultrafiltration (OR 3.68), ECMO (OR 3.63), 30-day mortality (HR 2.79), and 5-year mortality (HR 2.41) (p-value all <0.001). Patients who improved in the preoperative NT-proBNP risk had a significant 30-day and five-year survival benefit. Conclusions Preoperative NT-proBNP levels are independently associated with 30-day and five-year mortality after cardiac surgery. NT-proBNP reduction prior to surgery might decrease 30-day and five-year mortality after cardiac surgery.NTproBNP is associated with outcome

Activation of the CXCL12/CXCR4/ACKR3 axis is known to aid myocardial repair through ischemia-triggered hypoxia-inducible factor-1α (HIF-1α). To enhance the upregulation of HIF-1α, we administered roxadustat, a novel prolyl hydroxylase inhibitor (PHI) clinically approved by the European Medicines Agency 2021 for the treatment of renal anemia, with the purpose of improving LV function and attenuating ischemic cardiomyopathy. Methods: We evaluated roxadustat’s impact on HIF-1 stimulation, cardiac remodeling, and function after MI. Therefore, we analyzed nuclear HIF-1 expression, the mRNA and protein expression of key HIF-1 target genes (RT-PCR, Western blot), inflammatory cell infiltration (immunohistochemistry), and apoptosis (TUNEL staining) 7 days after MI. Additionally, we performed echocardiography in male and female C57BL/6 mice 28 days post-MI. Results: We found a substantial increase in nuclear HIF-1, associated with an upregulation of HIF-1α target genes like CXCL12/CXCR4/ACKR3 at the mRNA and protein levels. Roxadustat increased the proportion of myocardial reparative M2 CD206+ cells, suggesting beneficial alterations in immune cell migration and a trend towards reduced apoptosis. Echocardiography showed that roxadustat treatment significantly preserved ejection fraction and attenuated subsequent ventricular dilatation, thereby reducing adverse remodeling. Conclusions: Our findings suggest that roxadustat is a promising clinically approved treatment option to preserve myocardial function by attenuating adverse remodeling.

IntroductionThe potential for secondary use of health data to improve healthcare is currently not fully exploited. Health data is largely kept in isolated data silos and key infrastructure to aggregate these silos into standardized bodies of knowledge is underdeveloped. We describe the development, implementation, and evaluation of a federated infrastructure to facilitate versatile secondary use of health data based on Health Data Space nodes.Materials and methodsOur proposed nodes are self-contained units that digest data through an extract-transform-load framework that pseudonymizes and links data with privacy-preserving record linkage and harmonizes into a common data model (OMOP CDM). To support collaborative analyses a multi-level feature store is also implemented. A feasibility experiment was conducted to test the infrastructures potential for machine learning operations and deployment of other apps (e.g., visualization). Nodes can be operated in a network at different levels of sharing according to the level of trust within the network.ResultsIn a proof-of-concept study, a privacy-preserving registry for heart failure patients has been implemented as a real-world showcase for Health Data Space nodes at the highest trust level, linking multiple data sources including (a) electronical medical records from hospitals, (b) patient data from a telemonitoring system, and (c) data from Austria’s national register of deaths. The registry is deployed at the tirol kliniken, a hospital carrier in the Austrian state of Tyrol, and currently includes 5,004 patients, with over 2.9 million measurements, over 574,000 observations, more than 63,000 clinical free text notes, and in total over 5.2 million data points. Data curation and harmonization processes are executed semi-automatically at each individual node according to data sharing policies to ensure data sovereignty, scalability, and privacy. As a feasibility test, a natural language processing model for classification of clinical notes was deployed and tested.DiscussionThe presented Health Data Space node infrastructure has proven to be practicable in a real-world implementation in a live and productive registry for heart failure. The present work was inspired by the European Health Data Space initiative and its spirit to interconnect health data silos for versatile secondary use of health data.