Deutsches Herzzentrum München

Atherosclerotic cardiovascular disease (ASCVD) is a leading cause of morbidity and mortality globally. Low-density lipoprotein cholesterol is a causal risk factor for atherosclerotic cardiovascular disease, with multiple classes of cholesterol-lowering therapies effective at reducing atherosclerotic cardiovascular disease risk. Despite robust efficacy data from randomized trials, real-world implementation of guideline-recommended lipid-lowering therapies is suboptimal. Barriers to the implementation of guideline lipid-lowering therapy recommendations exist at the healthcare systems level, the medical therapy level, and the patient level. A combination of strategies, including the incorporation of quality improvement and cost-effectiveness analysis among payers, pharmacist-based educational initiatives, digital health tools directed towards patients, the simplification of drug regimens via polypill, and emerging novel therapies, including PCSK9 gene silencing and editing technologies, may bridge these implementation gaps. This review highlights challenges and solutions to alleviating barriers to optimal implementation of guideline-recommended lipid-lowering therapies.

Atrial tachycardias (AT) represent an increasingly common cause of morbidity and mortality. Driven by substantial advances in mapping and ablation technologies, the mechanistic understanding and therapeutic strategies for AT management have evolved rapidly in recent years, and catheter ablation is now regarded as the most effective strategy for maintaining sinus rhythm. Against this background, the recently published international clinical consensus statement on the management of patients with AT introduces, for the first time, astructured 10-point plan for "SMART-AT care" as aframework for the diagnosis and treatment of regular AT. This review highlights key developments and clinical implications, taking into account recent changes within the healthcare system.

Extracorporeal membrane oxygenation (ECMO) is widely used to treat cardiopulmonary failure after congenital heart surgery. This study evaluated patient characteristics, outcomes, and risk factors associated with perioperative venoarterial ECMO use. All patients undergoing congenital heart surgery between 2001 and 2024 at our centre were included. Prevalence, outcomes, risk factors for ECMO support, and predictors of in-hospital mortality following ECMO were analysed. Among 9892 congenital heart surgeries, ECMO was required in 178 (1.8%) for a median of 6 days (interquartile range [IQR] 4-9). Median age and weight at surgery were 2.8 months (IQR 0.4-25.2) and 4.1 kg (IQR 3.2-8.9), respectively. In patients ≤2 years, the Norwood procedure and surgery for coronary artery malformations were independent risk factors for ECMO support. Successful weaning was achieved in 62% (n = 111), while 17% (n = 30) required a second ECMO run. In-hospital mortality after ECMO was 55% (n = 98), occurring a median of 16 days (IQR 5-34) after surgery; 27% died after a successful first weaning. Model-based predictions showed an eight-fold increase between days 6 and 12 of ECMO support, with predicted mortality rising from 26% to 74%. Approximately 2% of patients undergoing congenital heart surgery require ECMO with overall survival around 50%. Prolonged ECMO duration and acute renal failure requiring renal replacement therapy were independently associated with mortality. The sharp increase in mortality beyond six days of ECMO highlights the need for early reassessment of reversibility and timely consideration of alternative strategies.

Sildenafil, a selective phosphodiesterase-5 (PDE5) inhibitor, supports vascular remodeling, but its effects on angiogenesis and regeneration of ischemic muscle tissue are not fully understood. We investigated the function of sildenafil by employing a murine hindlimb model of ischemia, in which ischemia and angiogenesis is induced by femoral artery ligation (FAL) in the lower leg of mice. Then, 7 days after FAL or sham operation, gastrocnemius muscles of sildenafil-treated and control mice were isolated and processed for histological and immunofluorescence analyses. Sildenafil treatment led to reduced apoptotic areas within the ischemic tissue (ascertained via TUNEL assay) and increased angiogenesis, evidenced by a higher capillary-to-muscle fiber ratio and an augmented number of proliferating capillary cells (CD31+/CD45-/BrdU+), compared to controls. We observed a decrease in the total count of leukocytes (CD45+) in sildenafil-treated mice. Regarding macrophage infiltration, we found a reduced total number of macrophages (CD68+), along with a shift in macrophage polarization toward the pro-angiogenic and anti-inflammatory M2-like phenotype (CD68+/MRC1+). In summary, we show that sildenafil treatment contributes to angiogenesis and the regeneration of ischemic muscle tissue, most likely by attenuating inflammatory responses and influencing macrophage polarization in direction to regenerative M2-like polarized macrophages.

We aimed to better understand patient characteristics and pathophysiological mechanisms associated with severe diastolic dysfunction in aortic stenosis patients undergoing transcatheter aortic valve implantation (TAVI). Patients with severe aortic stenosis often have echocardiographic signs of diastolic dysfunction. However, their characteristics and underlying disease mechanisms remain unclear. Untargeted LC–MS lipidomics (1110 lipids) and proteomics (834 proteins) were performed on peri-procedural plasma from 231 TAVI patients. Pre-procedural echocardiography was available in 191 patients. DIABLO (mixOmics, version 6.3.0, R version 4.4.1) was used to integrate lipidomic and proteomic profiles. Median age was 80 years, and 61% were female. In total, 75 (39%) patients had severe diastolic dysfunction. Patients with severe diastolic dysfunction more often had atrial fibrillation, higher plasma NT-proBNP concentrations, and more heart failure hospitalizations and mortality. Multi-omic network analysis identified two major lipid–protein clusters associated with severe diastolic dysfunction. The first showed dysregulation of membrane phospholipids such as cardiolipins (essential for mitochondrial integrity and energy metabolism), and phosphatidylserines (cytoprotective and anti-inflammatory properties). This cluster was associated with cytoskeletal and extracellular matrix remodeling. The second cluster showed high concentrations of acylcarnitines (indicative of metabolic dysfunction), which were associated with extracellular matrix remodeling and inflammatory responses. In patients with aortic stenosis undergoing TAVI, those with severe diastolic dysfunction showed a disrupted balance of membrane phospholipids and acylcarnitines, suggesting that impaired energy metabolism, cellular and extracellular structural remodeling, and inflammatory responses may underlie the development and progression of diastolic dysfunction and heart failure. We investigated clinical features and molecular profiles linked to severe diastolic dysfunction in aortic stenosis patients undergoing TAVI. Untargeted lipidomics (1110 lipids) and proteomics (834 proteins) were performed on peri-procedural plasma from 231 patients. Pre-procedural echocardiography was available in 191 patients. Severe diastolic dysfunction was present in 39% and was associated with atrial fibrillation, higher NT-proBNP, and more heart failure hospitalizations and mortality. Multi-omic integration identified two major lipid-protein clusters. The first was characterized by dysregulated membrane phospholipids, including cardiolipins and phosphatidylserines, linked to cytoskeletal and extracellular matrix remodeling. The other showed elevated acylcarnitines, indicating metabolic dysfunction, and inflammatory activation. These findings suggest that altered energy metabolism, structural remodeling, and inflammation are associated with severe diastolic dysfunction in aortic stenosis. Patients with severe aortic stenosis and severe diastolic dysfunction undergoing TAVI (n = 75 patients with severe diastolic dysfunction, n = 116 patients without severe diastolic dysfunction) show a disrupted balance of membrane phospholipids and acylcarnitines, suggesting that impaired energy metabolism, cellular and extracellular structural remodeling, and inflammatory responses may underlie the development and progression of diastolic dysfunction and heart failure. TAVI = transcatheter aortic valve replacement; LAVI = left atrial volume index; PASP = pulmonary artery systolic pressure; LA = left atrium; GLS = global longitudinal strain; LVMI = left ventricular mass index. • Diastolic dysfunction was linked to more atrial fibrillation and higher NT-proBNP. • Diastolic dysfunction predicted more HF admissions and mortality after TAVI. • Diastolic dysfunction was linked to altered phospholipid and acylcarnitine balance. • Metabolic impairments and inflammation may drive diastolic dysfunction in AS. • These mechanisms mirror those in heart failure with preserved ejection fraction.

The introduction of foundational models, specifically large language models, has promised a health care transformation. However, the field is rapidly evolving toward autonomous agent systems, defined as artificial intelligence (AI) entities that perceive and react to their environment to achieve specific goals-representing a paradigm shift from passive information retrieval to proactive, goal-oriented clinical assistance. Agentic AI systems transcend static knowledge limitations through core capabilities including persistent memory systems that maintain context across patient encounters, knowledge retrieval tools connecting to medical repositories through retrieval-augmented generation techniques, and computer use functionality enabling navigation of clinical software interfaces. Agentic workflows introduce sophisticated coordination mechanisms including hierarchical, collaborative, and sequential patterns demonstrating superior performance compared with single-agent approaches. Multiagent systems can autonomously coordinate entire clinical workflows across the entire radiology life cycle, from preacquisition protocol optimization through initial image analysis, specialized tool deployment, and preliminary report generation. However, successful clinical deployment requires systematic consideration of complexity thresholds, economic sustainability, cybersecurity frameworks, bias mitigation strategies, and appropriate governance structures. Critical challenges include managing the probabilistic nature of underlying models within deterministic clinical workflows, ensuring adequate human supervision, and preventing overcomplication of established processes. A structured four-phase implementation roadmap addresses these considerations through incremental progression from low-risk automation to comprehensive workflow orchestration while maintaining rigorous safety standards. As foundation models advance and interoperability standards mature, agentic AI will reshape radiology practice paradigms. Success depends on resolving stakeholder responsibility questions while orchestrating technological capabilities with clinical accountability, ensuring autonomous systems augment rather than replace professional judgment in pursuit of improved patient outcomes. Keywords: Informatics, Named Entity Recognition, Patient Scheduling/No-Show Prediction, Resource Allocation, Impact of AI on Education, Artificial Intelligence, Large Language Models, Agentic AI, Multi-Agent Systems, Radiology Workflow, Clinical Decision Support, Health Care Automation © RSNA, 2026.

Abstract Abstract A multifactorial porcine model of cardio-metabolic HFpEF highlights miR-483-3p as a promising target therapy. Background Heart failure with preserved ejection fraction (HFpEF) is associated with risk factors such as metabolic syndrome, diabetes, and hypertension, ultimately leading to endothelial dysfunction. Recent findings suggest a maladaptive role for miR-483-3p in endothelial cells and M2 macrophages in type 2 diabetes, but its role in HFpEF remains unclear. Purpose This study aimed to establish a multifactorial porcine model of cardio-metabolic HFpEF and investigate the expression of miR-483-3p during disease progression. Methods Adult female Göttingen minipigs (n=9) received subcutaneous drug-eluting implants releasing DOCA (50 mg/kg BW) for 60 days and were fed a high-fat, high-fructose, high-cholesterol, high-salt diet for 20 weeks. Assessments were performed every 4 weeks, including blood pressure, echocardiography, blood sampling, and at Week 20, invasive hemodynamic measurements (PCWP, LV conductance catheter), and coronary flow reserve (CFR). Six (n=6) adult female Göttingen minipigs, without DOCA and fed a standard diet, were used as controls and underwent the same investigations as the HFpEF animals. Results Animals developed a metabolic syndrome, including obesity, dyslipidaemia and glucose intolerance. Although the LVEF remained preserved throughout the study by echocardiography, cardiac remodeling was evident. This manifested as concentric LV hypertrophy, since the relative wall thickness (RWT) increased from 0.47 ± 0.11 (Week 0) to 0.73 ± 0.19 (Week 20). The control animals maintained their value of 0.49 ± 0.11. At Week 20, HFpEF animals were hypertensive (SBP: 182,8 ± 20,4mmHg vs. 114,1 ± 9,1mmHg; DBP: 127,3 ± 9,06mmHg vs. 63,0 ± 18,04mmHg; mAOP: 134,0 ± 18,02mmHg vs. 76,5 ± 10,8mmHg), showed a PCWP of 17,2±5,4mmHg and a compromised CFR (1.26±0.15 vs 2.10±0.3). LV PV-loop assessment revealed increased end-diastolic pressure (20.16±7.35 vs 9.96 ± 2.0 mmHg), as well as stroke work (5197 ± 1191J vs. 3299 ± 816J) and potential energy (1193 ± 217J vs. 722,5 ± 187.5J). Notably, the expression profile of miR-483-3p showed a continuous increase throughout the disease progression, reaching a plateau at week 12 with an approximately 1000-fold increase compared to baseline in M2 macrophages. In circulating plasma, miR-483-3p expression, normalized to the housekeeping gene miR-16-5p, was elevated up to 8-fold in the HFpEF group at weeks 12, 16, and 20 compared to the control group. Conclusion This study successfully establishes a clinically relevant porcine model of cardio-metabolic HFpEF. The progressive upregulation of miR-483-3p correlates with disease severity, supporting its potential as a therapeutic target in HFpEF.

Rapid and accurate detection of coronary plaques on CCTA is critical for timely CAD diagnosis but is limited by reader workload and interobserver variability. Our objective was to evaluate the effectiveness of machine learning (ML) based on automated segmentation of coronary plaques in coronary computed tomography angiography (CCTA). We retrospectively analyzed CCTA scans from 1,642 patients (4,711 training vessels, 1,112 test vessels, plus 1,613 negative vessels) using an nnU-Net 3D full resolution architecture. Hyperparameters (batch size, learning-rate scheduler, epochs) were optimized on a 10% subset of the training dataset, and the final model was trained with 5-fold cross-validation on positive cases. Test performance was assessed at the plaque, vessel, and exam levels. Of 2,090 ground-truth plaques, the model achieved 1,772 TP for 84.8% sensitivity (95% CI 83.2-86.3%), 382 FP for 82.3% precision (95% CI 80.6-83.8), and a median Dice score of 0.88 (95% CI 0.87-0.89). At the vessel level, sensitivity was 94.7% (95% CI 93.2-95.9%) and specificity was 84.9% (95% CI 83.0-86.5%). At the examination level, sensitivity was 97.4% (95% CI 94.5-98.8%) and specificity was 79.7% (95% CI 76.5-82.6%). Detection of small, non-calcified plaques remained challenging, and false positives were often due to motion or step artifacts. Our model showed promising results in detecting coronary plaques in CCTA examinations, particularly for medium to large plaques and high negative predictive value for ruling out significant CAD, offering potential to streamline radiology workflows. Future work will focus on small-plaque detection, artifact robustness, and multi-center validation to enhance clinical utility.

Pathogen reduction treatment (PRT) of platelet concentrates (PC) is one of the most recent advances in improving blood safety and lowering the risk of transfusion-transmitted diseases. The characteristics of PR-treated PC differ slightly from those of untreated PC and may affect transfusion outcomes. We established how effective PRT methods, (INTERCEPT™ Blood System) PC are when transfused to cardiac surgery patients. This study examined the influence of PRT using amotosalen and UVA light in a population of cardiac surgery patients. We analysed bleeding and platelet drop following cardiopulmonary bypass (CPB) surgery. We selected 73 patients after considering the medical exclusion criteria: 46 patients transfused with untreated platelet concentrate versus 27 patients transfused with PRT-treated platelet concentrate. Data analysis concerns the readout after the first platelet concentrate transfusion. The decrease in patient platelet count between pre-operative and H0 [Intensive Care Unit (ICU) admission], and pre-operative and H6 post-surgery did not differ significantly with or without PRT. The volume of postoperative bleeding after CPB surgery did not differ significantly regardless of whether the patient was transfused with PRT-PC or untreated PC. No difference was documented between the groups in terms of postoperative pulmonary infection rate. Regardless of the use of platelet PRT, among the factors associated with bleeding, only Fg level was independently and significantly associated. A 1mg/L increase in fibrinogen (pre-operative) is associated with a 159mL decrease in bleeding 24hours post-surgery. In postoperative cardiac surgery, the use of platelets treated with amotosalen/UVA for pathogen reduction does not appear to affect transfusion effectiveness and postoperative bleeding.