Daniel Oehler

Background: Three-dimensional (3D) mapping of the left atrium (LA) using multipolar high-density (HD) catheters plays a central role in contemporary LA ablation procedures, as accurate and efficient acquisition of anatomical and electrophysiological information is essential. This study benchmarks workflow efficiency during acquisition of a predefined complete HD LA map across four widely used multipolar HD catheter designs. The analysis focuses on efficiency metrics and does not aim to assess mapping quality, arrhythmia interpretation accuracy, or clinical outcomes. Methods: We analyzed 182 consecutive patients from an ongoing cohort undergoing LA procedures, including pulmonary vein isolation and complex LA ablations, using 3D mapping in accordance with current guideline recommendations. Four multipolar HD catheters were applied according to the respective 3D mapping systems: a basket catheter (Orion, Rhythmia), a grid catheter (HD Grid, EnSite X), a penta-spline catheter (PentaRay, Carto 3), and an octa-spline catheter (OctaRay, Carto 3). For each procedure, the time required for acquisition of a complete 3D LA map and the number of acquired points were systematically recorded. LA HD mapping speed was calculated by relating LA volume to the time required for complete map acquisition. Results: The study population had a mean age of 69 years, with a median CHA₂DS₂-VASc score of 3, indicating a cohort with a moderate thromboembolic risk profile. The median LA volume index (LAVI) was 34 mL/m². Patients were distributed across four HD catheter groups, comprising 44 patients in the basket group, 29 in the grid group, 23 in the penta-spline group, and 86 in the octa-spline group. LA mapping speed differed significantly among the groups, with values of 3 mL/min in the basket group, 2.5 mL/min in the grid group, 3.1 mL/min in the penta-spline group, and the highest mapping speed observed in the octa-spline group at 5.9 mL/min. Conclusions: The octa-spline catheter was associated with a significantly higher LA mapping speed compared with other widely used HD catheters.

Acute hypoxia triggers multiple physiological and immune responses, yet the immediate systemic effects on circulating complement proteins remain insufficiently characterized. The complement cascade plays a central role in inflammation, host defense, and ischemia-related tissue injury, but its regulation during transient oxygen deprivation and reoxygenation in humans is poorly understood. Sixteen healthy volunteers were exposed to stepwise normobaric hypoxia simulating altitudes of 0, 2, 4, and 6 km (pO₂ = 9.64 kPa) followed by reoxygenation under normoxic conditions. Blood samples were collected at baseline, peak hypoxia (6 km), and after reoxygenation. Quantitative plasma proteomics was performed using targeted multiple-reaction-monitoring mass spectrometry to quantify key complement components (C1 complex, C3–C9, factor B) in 16 participants with complete datasets. Hematological parameters were analyzed in parallel. Hypoxia transiently increased leukocyte and platelet count, whereas hematocrit and mean corpuscular volume slightly decreased. While only slightly increasing during hypoxia, most complement peptides - including C1S, C1R, C3, C5, C7, C9, and CFAB - showed a coordinated reduction in relative abundance upon reoxygenation compared to both baseline and hypoxia (median fold-change ≈ 0.6–0.8; p < 0.05). Correlation analysis revealed coherent clustering among complement components but only weak associations with hematological indices. Acute hypoxia elicits rapid and reversible changes in the circulating complement peptide pool in healthy humans. Targeted plasma proteomics demonstrates clear oxygen-phase–dependent dynamics, with a coordinated decrease after reoxygenation. This pattern is consistent with reduced circulating availability of complement components, activation-associated consumption, and/or redistribution within the intravascular compartment. Future validation of these findings in certain patient cohorts may define translational relevance and functional consequences. Graphical abstract Sixteen healthy volunteers were exposed to stepwise normobaric hypoxia simulating altitudes of 0 km, 2 km, 4 km, and 6 km. Hypoxia increased plasma concentrations of several proteins of the complement system as analyzed by quantitative mass spectrometry. Upon reoxygenation, most complement peptides decreased to or below baseline.

Background/Objectives: Acute myocardial infarction (AMI), characterized by irreversible heart muscle damage and impaired cardiac function caused by myocardial ischemia, is a leading cause of global mortality. The damage associated with reperfusion, particularly mitochondrial dysfunction and reactive oxygen species (ROS) formation, has emerged as a crucial factor in the pathogenesis of cardiac diseases, leading to the recognition of mitochondrial proteins as potential markers for myocardial damage. This study aimed to identify differentially expressed proteins based on the type of cardiac injury, in particular those with and without reperfusion. Methods: Male C57Bl/6J mice were either left untreated, sham-operated, received non-reperfused AMI, or reperfused AMI. Twenty-four hours after the procedures, left ventricular (LV) function and morphological changes including infarct size were determined using echocardiography and triphenyl tetrazolium chloride (TTC) staining, respectively. In addition, plasma was isolated and subjected to untargeted mass spectrometry and, further on, the ELISA-based validation of candidate proteins. Results: We identified mitochondrial creatine kinase 2 (Ckmt2) as a differentially regulated protein in plasma of mice with reperfused but not non-reperfused AMI. Elevated levels of Ckmt2 were significantly associated with infarct size and impaired LV function following reperfused AMI, suggesting a specific involvement in reperfusion damage. Conclusions: Our study highlights the potential of plasma Ckmt2 as a biomarker for assessing reperfusion injury and its impact on cardiac function and morphology in the acute phase of MI.

Expansion of the glutamine tract (poly-Q) in the protein huntingtin (HTT) causes the neurodegenerative disorder Huntington’s disease (HD). Emerging evidence suggests that mutant HTT (mHTT) disrupts brain development. To gain mechanistic insights into the neurodevelopmental impact of human mHTT, we engineered male induced pluripotent stem cells to introduce a biallelic or monoallelic mutant 70Q expansion or to remove the poly-Q tract of HTT. The introduction of a 70Q mutation caused aberrant development of cerebral organoids with loss of neural progenitor organization. The early neurodevelopmental signature of mHTT highlighted the dysregulation of the protein coiled-coil-helix-coiled-coil-helix domain containing 2 (CHCHD2), a transcription factor involved in mitochondrial integrated stress response. CHCHD2 repression was associated with abnormal mitochondrial morpho-dynamics that was reverted upon overexpression of CHCHD2. Removing the poly-Q tract from HTT normalized CHCHD2 levels and corrected key mitochondrial defects. Hence, mHTT-mediated disruption of human neurodevelopment is paralleled by aberrant neurometabolic programming mediated by dysregulation of CHCHD2, which could then serve as an early interventional target for HD.

Gravitational changes between micro- and hypergravity cause several adaptations and alterations in the human body. Besides muscular atrophy and immune system impairment, effects on the circulatory system have been described, which can be associated with a wide range of blood biomarker changes. This study examined nine individuals (seven males, two females) during a parabolic flight campaign (PFC). Thirty-one parabolas were performed in one flight day, resulting in ~22 s of microgravity during each parabola. Each participant was subjected to a single flight day with a total of 31 parabolas, totaling 11 min of microgravity during one parabolic flight. Before and after (1 hour (h) and 24 h), the flights blood was sampled to examine potential gravity-induced changes of circulating plasma proteins. Proximity Extension Assay (PEA) offers a proteomic solution, enabling the simultaneous analysis of a wide variety of plasma proteins. From 2925 unique proteins analyzed, 251 (8.58%) proteins demonstrated a differential regulation between baseline, 1 h and 24 h post flight. Pathway analysis indicated that parabolic flights led to altered levels of proteins associated with vesicle organization and apoptosis up to 24 h post microgravity exposure. Varying gravity conditions are associated with poorly understood physiological changes, including stress responses and fluid shifts. We provide a publicly available library of gravity-modulated circulating protein levels illustrating numerous changes in cellular pathways relevant for inter-organ function and communication.

Background: Neurologic events during primary stay in heart transplant (HTx) recipients may be associated with reduced outcome and survival, which we aim to explore with the current study. Methods and Results: We screened and included all patients undergoing HTx in our center between September 2010 and December 2022 (n=268) and checked for the occurrence of neurologic events within their index stay. Neurologic events were defined as ischemic stroke, hemorrhage, hypoxic ischemic injury, or acute symptomatic neurologic dysfunction without central nervous system injury. The cohort was then divided into recipients with (n=33) and without (n=235) neurologic events after HTx. Using a multivariable Cox regression model, the association of neurologic events after HTx and survival was assessed. Recipients with neurologic events displayed a longer intensive care unit stay (30 versus 16 days; P =0.009), longer mechanical ventilation (192 versus 48 hours; P P =0.01). Resternotomy (36% versus 26%; P =0.05) and mechanical life support (extracorporeal life support) after HTx (46% versus 24%; P =0.02) were also significantly higher in patients with neurologic events. Covariable‐adjusted multivariable Cox regression analysis revealed a significant independent association of neurologic events and increased 30‐day (hazard ratio [HR], 2.5 [95% CI, 1.0–6.0]; P =0.049), 1‐year (HR, 2.2 [95% CI, 1.1–4.3]; P =0.019), and overall (HR, 2.5 [95% CI, 1.5–4.2]; P P <0.001). Conclusions: Neurologic events after HTx were strongly and independently associated with worse postoperative outcome and reduced survival up to 5 years after HTx.

Donor hearts frequently originate from donors whose lungs are also recovered for transplant. Synchronous heart and lung procurement is more complex than procurement ofthe heart alone, and the effects on outcomes are debated. This study examines the effect of synchronous procurement on outcomes in heart transplant recipients. This single-center study included patients who received a heart transplant from September 2010 to June 2022. Main outcomes were overall mortality and mortality at 30 days, 3 months, 1 year, and 3 years and morbidity within the first year. We analyzed overall mortality using KaplanMeier survival analysis. Logistic regression was used for the remaining outcomes, adjusting for covariates. P < .05 was considered significant. Our study included 253 heart transplant recipients (72.3% male, mean age 55.0 years), of which 184 patients (72.7%) received hearts from donors of heart and lung, and 69 (27.3%) received hearts from donors of only hearts. Heart-and-lung donors were younger than heart-only donors (43.2 vs 47.2 years; P = .017). Transplant recipient baseline characteristics were not different between the 2 groups. Receipt of hearts from heart-and-lung donors was not associated with higher overall mortality (P = .33) or mortality at 3 months (P = .199), 1 year (P = .348), or 3 years (P = .375), and even showed better 30-day survival than receipt of hearts from heart-only donors (p=0.035). Recipients of hearts from heart-and-lung donors did not have higher rates of postoperative mechanical circulatory support, resternotomy, or pacemaker implantation within the first year. Our study confirms that synchronous heart and lung procurement for transplant is not associated with worse outcomes in heart transplant recipients and that hearts originating from heart-andlung donors may even be associated with improved outcomes.

Myat Soe Thet et al. published a letter

In-hospital cardiac arrest (IHCA) is associated with high mortality and poor neurological outcomes. Our objective was to assess whether the lactate-to-albumin ratio (LAR) can predict the outcomes in patients after IHCA. We retrospectively screened 75,987 hospitalised patients at a university hospital between 2015 and 2019. The primary endpoint was survival at 30-days. Neurological outcomes were assessed at 30 days using the cerebral performance category scale. 244 patients with IHCA and return of spontaneous circulation (ROSC) were included in this study and divided into quartiles of LAR. Overall, there were no differences in key baseline characteristics or rates of pre-existing comorbidities among the LAR quartiles. Patients with higher LAR had poorer survival after IHCA compared to patients with lower LAR: Q1, 70.4% of the patients; Q2, 50.8% of the patients; Q3, 26.2% of the patients; Q4, 6.6% of the patients (p = 0.001). Across increasing quartiles, the probability of a favourable neurological outcome in patients with ROSC after IHCA decreased: Q1: 49.2% of the patients; Q2: 32.8% of the patients; Q3: 14.7% of the patients; Q4: 3.2% of the patients (p = 0.001). The AUCs for predicting 30-days survival using the LAR were higher as compared to using a single measurement of lactate or albumin. The prognostic performance of LAR was superior to that of a single measurement of lactate or albumin for predicting survival after IHCA.

Intro: Recently, the impact of circadian rhythm and daytime variation on surgical outcomes has attracted interest. Although studies for coronary artery and aortic valve surgery report contrary results, effects on heart transplantation have not been studied.Methods: Between 2010 and February 2022, 235 patients underwent HTx in our department. The recipients were reviewed and categorized according to the start of the HTx procedure – between 04:00 am and 11:59 am (morning, n = 79), 12:00 pm and 07:59 pm (afternoon, n = 68) or 08:00 pm and 03:59 am (night, n = 88).Results: The incidence of high urgency status was slightly but not significantly increased (p = .08) in the morning (55.7%), compared to the afternoon (41.2%) or night (39.8%). The most important donor and recipient characteristics were comparable among the three groups. The incidence of severe primary graft dysfunction (PGD) requiring extracorporeal life support (morning: 36.7%, afternoon: 27.3%, night: 23.0%, p = .15) was also similarly distributed. In addition, there were no significant differences for kidney failure, infections, and acute graft rejection. However, the incidence of bleeding that required rethoracotomy showed an increased trend in the afternoon (morning: 29.1%, afternoon: 40.9%, night: 23.0%, p = .06). 30‐day survival (morning: 88.6%, afternoon: 90.8%, night: 92.0%, p = .82) and 1‐year survival (morning: 77.5%, afternoon: 76.0%, night: 84.4%, p = .41) were comparable between all groups.Conclusion: Circadian rhythm and daytime variation did not affect the outcome after HTx. Postoperative adverse events as well as survival were comparable throughout day‐ and night‐time. As the timing of the HTx procedure is rarely possible and depends on the timing of organ recovery, these results are encouraging, as they allow for the continuation of the prevalent practice.