Christoph Liebetrau

Background: Fibroblast growth factor-23 (FGF23) is a key regulator of phosphate homeostasis and an emerging biomarker in cardiovascular disease. Emerging data suggest that FGF23 may also contribute to the pathophysiology of myocardial infarction (MI), but existing studies have largely focused on non-acute stages. To address this gap, we investigated early FGF23 regulation by characterizing serum concentration kinetics over the first 24 h following MI, using both a clinical MI model (TASH) and a cohort of patients with ST-elevation myocardial infarction (STEMI). Methods: Circulating FGF23 concentrations (cFGF23; RU/mL) were determined by C-terminal ELISA in patients with preserved renal function (eGFR > 30 mL/min/1.73 m²). TASH (transcoronary septal ablation) was carried out in patients with hypertrophic obstructive cardiomyopathy (n = 38). Venous serum samples were taken at baseline (pre-TASH) and at 30′, 60′, 2 h, 4 h and 24 h post-TASH. For the STEMI cohort (n = 18), serum was sampled immediately before and 3 h after coronary recanalization. All samples were processed using standardized procedures prior to analysis. Changes over time were assessed using the Friedman test with Bonferroni-corrected pairwise Wilcoxon comparisons. Results: FGF23 concentrations changed significantly over time after TASH (Friedman test, p < 0.000001, Kendall’s W = 0.518). Baseline FGF23 was 28.9 (19.4–71.0) RU/mL and increased significantly at 30′ (68.2 (36.2–178.7) RU/mL, adjusted p < 0.0001 **) after TASH. Concentrations remained elevated at 60′ (54.8 (31.6–118.3) RU/mL; adjusted p = 0.0019 *), returned to baseline at 2 h (30.9 (20–71.2) RU/mL; adjusted p = 1.0 vs. baseline) and decreased significantly below baseline at 4 h (24 (12.13–37.5) RU/mL, adjusted p = 0.0215 *). By 24 h, FGF23 had returned to baseline levels (28.8 (12.8–57.3) RU/mL; adjusted p = 1.0 vs. baseline). Although concentrations were numerically higher than at the 4 h nadir, this recovery did not reach statistical significance (adjusted p = 0.136 vs. 4 h). In STEMI patients, a non-significant decrease was observed from baseline (27 (15.5–35.75) RU/mL) to 3 h after recanalization (15.5 (6.75–34.25) RU/mL; p = 0.074, effect size r = 0.422). In an exploratory normalized analysis, the decline reached significance (p = 0.0241). Conclusions: The triphasic kinetics of circulating FGF23 in TASH patients—characterized by an early rise, transient undershoot, and a recovery toward baseline with a continuing upward trend—are consistent with a dynamic release-and-clearance pattern following myocardial injury. These findings are hypothesis-generating and warrant further investigation in larger cohorts with additional biomarkers to elucidate the source, regulation, and potential functional significance of FGF23 in the acute phase of myocardial infarction.

Background: Elevated Lipoprotein(a) Lp(a) levels are associated with coronary atherosclerosis as detected by cardiac computed tomography angiography (CCTA). However, quantitative data including coronary plaque volumes and characteristics are scarce. The current study evaluated the sex-specific correlations between (Lp(a)) levels and the extent and composition of coronary stenosis and plaques. Methods: 1,946 patients undergoing CCTA (third-generation dual-source scanner) for suspected coronary artery disease were included whose Lp(a) levels were available. Lp(a) values ≥ 125 nmol/L were classified as high. Results: High Lp(a) levels were observed in 336 patients, who had greater maximum degree of stenosis (49.5 ± 26.4% vs. 43.5 ± 27.6%, P = 0.002), mainly as a result of the pronounced difference in males (53.8 ± 26.0% vs. 46.2 ± 26.8%, P = 0.001). A strong correlation between higher Lp(a) values and high-risk plaque features was noted in the overall cohort (odds ratio [OR]: 1.645; 95% confidence interval [CI]: 1.011 to 2.593; P = 0.037), independent of age and LDL-cholesterol values. In males, high Lp(a) levels were associated with greater total plaque volumes (118.1 [IQR 18.3–284.4] vs. 83.2 [IQR 11.8–226.3] mm ³ , P = 0.018, Pint = 0.09), including fibrotic components (27.6 [IQR 2.1–109.9] vs. 18.2 [IQR 0.4–65.0] mm ³ , P = 0.011, Pint = 0.013), whereas in women, only a marginal linear correlation with total plaque volume was observed (19.2 vs. 8.1 mm ³ ; Spearman’s rank correlation R = 0.16, P = 0.037). Conclusions: Our study identifies novel sex-specific correlations between Lp(a) levels and coronary plaque characteristics. High Lp(a) levels in men seems to be associated with increased fibrotic plaque volumes and may contribute to greater total plaque burden and high-risk plaque features. Graphical

Chronic thromboembolic pulmonary hypertension (CTEPH) leads to progressive right ventricular (RV) dysfunction. Pulmonary endarterectomy (PEA) is an established treatment for these patients; however, the molecular mechanisms underlying RV remodeling and recovery remain poorly understood. Here we show that RNA sequencing and histological analysis of RV free wall and septal biopsies from patients with CTEPH reveal extracellular matrix enrichment and cytoskeletal remodeling before PEA. These changes were consistent across an exploratory and confirmatory cohort. Post-PEA samples showed reversal of both histological and transcriptional abnormalities. Key signaling molecules—ANKRD1, IL7R and SERPINE1—were implicated in fibrotic and proliferative pathways, as confirmed in human tissues and experimental models. Our findings identify a reversible gene expression and structural remodeling signature in the RV, linking hemodynamic unloading with molecular recovery. These insights suggest potential therapeutic targets to modulate maladaptive RV remodeling in CTEPH and improve outcomes beyond surgical intervention.

Background The preference for using transradial access (TRA) over transfemoral access (TFA) in patients requiring coronary intervention is based on evidence suggesting that TRA is associated with less bleeding and vascular complications, shorter hospital stays, improved quality of life, and a potential beneficial effect on mortality. We have limited study data comparing both access routes in a patient population with atrial fibrillation undergoing PCI, who have a particular increased risk of bleeding, while AF itself is associated with an increased risk of thromboembolism. Methods Using data from the RIVA-PCI registry, which includes atrial fibrillation patients undergoing PCI, we analyzed a high-bleeding-risk cohort. These patients were predominantly on oral anticoagulation (OAC) for atrial fibrillation and the PCI was performed via radial or femoral access. Endpoints examined were in-hospital bleeding (BARC 2-5), cerebral events (TIA, hemorrhagic or ischemic stroke) and coronary events (stent thrombosis and myocardial infarction). Results Out of 1636 patients, 854 (52.2%) underwent transfemoral access (TFA), while 782 (47.8%) received the procedure via transradial access (TRA), including nine patients with brachial artery puncture. Mean age was 75.5 years. Groups were similar in terms of age, sex distribution, atrial fibrillation type, cardiovascular history, risk factors, and comorbidities, except for a higher incidence of previous bypass surgeries, heart failure, hyperlipidemia, and chronic kidney disease (CKD) with GFRConclusions In high-bleeding-risk (HBR) patients with atrial fibrillation (AF) undergoing PCI for acute or chronic coronary syndrome, utilizing radial access (TRA) resulted in a significant decrease of in-hospital bleeding, while not increasing the risk of embolic or ischemic events compared to femoral access.

Zusammenfassung Die interventionelle Behandlung von Hochrisikopatienten bleibt weiter herausfordernd und hat trotz aller technischen Neuerungen ein hohes Verbesserungspotenzial. Mechanische Kreislaufunterstützungssysteme (MCS) können in Abhängigkeit von der klinischen Situation sinnvoll sein, wenngleich eine eindeutige Studienlage hierfür bisher fehlt. Die koronare Mehrgefäßerkrankung und ein hoher SYNTAX-Score in Verbindung mit einer eingeschränkten Ventrikelfunktion sind eine mögliche Prädiktorenkombination für einen MCS-Einsatz, der das höhere Komplikationsrisiko rechtfertigt.

The main aim of this study was to assess the prognostic utility of TAPSE/PASP as an echocardiographic parameter of maladaptive RV remodeling in cardiomyopathy patients using cardiac magnetic resonance (CMR) imaging. Furthermore, we sought to compare TAPSE/PASP to TAPSE. The association of the echocardiographic parameters TAPSE/PASP and TAPSE with CMR parameters of RV and LV remodeling was evaluated in 111 patients with ischemic and non-ischemic cardiomyopathy and cut-off values for maladaptive RV remodeling were defined. In a second step, the prognostic value of TAPSE/PASP and its cut-off value were analyzed regarding mortality in a validation cohort consisting of 221 patients with ischemic and non-ischemic cardiomyopathy. A low TAPSE/PASP (<0.38 mm/mmHg) and TAPSE (<16 mm) were associated with a lower RVEF and a long-axis RV global longitudinal strain (GLS) as well as higher RVESVI, RVEDVI and NT-proBNP. A low TAPSE/PASP, but not TAPSE, was associated with a lower LVEF and long-axis LV GLS, and a higher LVESVI, LVEDVI and T1 relaxation time at the interventricular septum and the RV insertion points. Furthermore, in the validation cohort, low TAPSE/PASP was associated with a higher mortality and TAPSE/PASP was an independent predictor of mortality. TAPSE/PASP is a predictor of maladaptive RV and LV remodeling associated with poor outcomes in cardiomyopathy patients.

Background: Percutaneous mitral valve repair (PMVR) in high-risk patients is currently controversial, especially in those with secondary mitral regurgitation (MR). Exercise pulmonary hemodynamics may help to unmask cardiac dysfunction as well as the dynamic impact of MR. The present study sought to explore the clinical impact of preprocedural exercise right heart catheterization (RHC) for the selection of patients who could most benefit from PMVR. Methods: Sixty-eight patients with symptomatic primary and secondary MR and exercise RHC before PMVR were included in this retrospective analysis of the association of exercise RHC parameters with survival and improvement in New York Heart Association class within 12 months. Results: Median patient age was 77 years (±8.5), 37% were female, and 81% presented with New York Heart Association class III. A total of 65% of the patients had left ventricular ejection fraction P P <0.001), and 79% of patients with ΔV-wave ≥15 mm Hg were in New York Heart Association class I or II at follow-up (<15 mm Hg: 28%). These results were for the most part confirmed in the subgroup of patients with secondary MR (65%). Conclusions: In our cohort of patients with indication for PMVR, preprocedural exercise RHC was able to identify patients with an unfavorable outcome. Further studies with larger patient numbers are warranted before this approach can be implemented in a structured diagnostic workup of patients under evaluation for PMVR.

Background: Event adjudication by a clinical event committee (CEC) provides a standardized, independent outcome assessment. However, the added value of CEC to investigators reporting remains debated. GLASSY (GLOBAL LEADERS Adjudication Sub-Study) implemented, in a subset of the open-label, investigator-reported (IR) GLOBAL LEADERS trial, an independent adjudication process of reported and unreported potential outcome events (triggers). We describe metrics of GLASSY feasibility and efficiency, diagnostic accuracy of IR events, and their concordance with corresponding CEC-adjudicated events. Methods: We report the proportion of myocardial infarction, bleeding, stroke, and stent thrombosis triggers with sufficient evidence for assessment (feasibility) that were adjudicated as outcome events (efficiency), stratified by source (IR or non-IR). Using CEC-adjudicated events as criterion standard, we describe sensitivity, specificity, positive and negative predictive value, and global diagnostic accuracy of IR events. Using Gwet AC coefficient, we examine the concordance between IR- and corresponding CEC-adjudicated triggers. There was sufficient evidence for assessment for 2592 (98.3%) of 2636 triggers. Results: Overall, the adjudicated end point-to-trigger ratio was high and similar between IR- (88%) and non-IR–reported (87%) triggers. The global diagnostic accuracy and concordance between IR-reported and CEC-adjudicated outcome events was 0.70 (95% CI, 0.65–0.74) and 0.54 (95% CI, 0.45–0.62), respectively, for myocardial infarction; 0.77 (95% CI, 0.75–0.79) and 0.71 (95% CI, 0.68–0.74) for bleeding; 0.70 (95% CI, 0.62–0.79) and 0.59 (95% CI, 0.43–0.74) for stroke; 0.59 (95% CI, 0.52–0.66) and 0.39 (95% CI, 0.25–0.53) for stent thrombosis. For IR bleedings, the concordance with the CEC on type of events was generally weak. Conclusions: Implementing CEC adjudication in a pragmatic open-label trial with IR events is feasible and efficient. Our findings of modest global diagnostic accuracy for IR events and generally weak concordance between investigators and CEC support the role for CEC adjudication in such settings. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT03231059.