Das Posturale orthostatische Tachykardie Syndrom (POTS) ist eine Störung des autonomen Nervensystems, die in ca. 30-50% der Fälle nach viralen Infektionen auftritt oder als Symptom internistischer, kardiologischer oder neurologischer Erkrankungen entstehen kann [1]. Klinisch bestehen neben typischen, lageabhängigen (orthostatischen) Beschwerden wie Belastungsintoleranz, Schwindel oder Palpitationen auch begleitende Symptome wie Fatigue oder kognitive Störungen [2]. Seit der COVID Pandemie werden ähnliche Symptome bei Post COVID-Betroffenen berichtet. In der Literatur wird POTS bei bis zu 30 % der PC-Betroffenen beobachtet [3,4]. Wir untersuchten, wie häufig hämodynamische Kriterien eines POTS bei chronischen Post COVID-Betroffenen in der Rehabilitation zu beobachten sind und ob sich dadurch ein PC Subtypus definieren lässt.
Methode:
Rehabilitationspatient*innen mit gesichertem, chronifiziertem Post COVID-Syndrom (Erkrankungsdauer > 9 Monate, Diagnose verifiziert durch > 2 Experten) wurden mittels standardisiertem Liege-/Steh-Test (5/10 min, nüchtern, vormittags) untersucht und nach Leitkriterien automatisiert ausgewertet (Abb.1). Zusätzlich wurden Kardinalsymptome des Post COVID-Syndroms sowie deren Häufigkeit und Intensität auf einer Skala von 1-10 systematisch erfasst. Anämien, Schilddrüsendysfunktion, Herzrhythmusstörung oder neurologische Ursachen (z.B. PNP, Parkinson) wurden ausgeschlossen.
Ergebnisse:
Es wurden Daten von 226 PC-Betroffenen (median 47 Jahre, 70% w) erhoben. 28 % zeigten hämodynamische Kriterien eines POTS (POTS+) im Stehtest. Bei allen PC-Betroffenen lag eine substanzielle Fatigue vor. Vegetative Symptome (Schwindel, Palpitationen) wurden von einem Großteil der Betroffenen über die letzten Monate berichtet (Abb. 2). Zwischen POTS+ und POTS-negativen (POTS-) PC-Betroffenen zeigten sich keine signifikanten Unterschiede der Symptome (Abb.2). Es bestand ein leichter statistisch signifikanter Zusammenhang zwischen dem POTS+ und dem Geschlecht: weibliche Patientinnen hatten etwas häufiger POTS.
Schlussfolgerung:
Bei einer relevanten Subgruppe von langzeitig PC-Betroffenen konnte eine Störung der Kreislaufregulation wie bei POTS durch einen standardisierten 15-Minuten-Steh-Test objektiviert werden. Dabei bestand ein vollständiger Symptom-Overlap zwischen den POTS+ und POTS- PC-Betroffenen. Die Diagnose eines POTS bei PC-Betroffenen erlaubt spezifische Therapieansätze (Kreislauftraining, Kompressionstherapie, Elektrolyte/Medikation) sowie die Intensitätssteuerung (Pacing). Ursachen der autonomen Dysfunktion (neuronal, chemosensorisch, endokrin) als auch die Prognose bleiben weiter zu klären.

Introduction: Atherosclerosis, the primary cause of coronary artery disease (CAD), is characterized by chronic arterial inflammation driven by LDL-cholesterol (LDL-C) accumulation and an autoimmune response involving autoreactive CD4+ T cells recognizing ApoB100 peptides. T regulatory cells (Tregs) counteract this response by secreting anti-inflammatory cytokines, such as IL-10. However, murine studies suggest that Tregs may adopt a pro-inflammatory phenotype over time, ultimately promoting CAD progression. We investigated circulating Tregs in human CAD patients to assess phenotypic changes and their potential role in CAD progression.

Methods: The ANIMATE clinical trial included 359 patients at high cardiovascular risk or with a history of CAD at the University Heart Centre Freiburg-Bad Krozingen, Germany. In a case-control study design, we selected 80 patients matched by their clinical parameters into four groups: young (≤55 years) without (n=19) or with CAD (n=21), and old (≥70 years) without (n=18) or with CAD (n=22). Tregs (CD4+/CD127-/CD25+/FoxP3+ T cells) were analyzed by flow cytometry for frequency, activation marker expression, and cytokine secretion following PMA stimulation.

Results: Younger patients showed no significant differences in Treg numbers with or without CAD. Older CAD patients exhibited a 2-fold increase in circulating Tregs compared to those without CAD (p=0.0036), but showed reduced IL-10 expression by 70% and increased IL-17, TNF-α, and IFN-γ production. While in younger patients Tregs sustained their atheroprotective function, these findings suggest a shift towards a proinflammatory phenotype in older CAD patients. Treg numbers were higher in patients with arterial hypertension, severe CAD (3-vessel disease), or prior myocardial infarction, while correlated positively with anti-ApoB IgG but negatively with LDL-C levels.

Conclusion: Older CAD patients display increased but dysfunctional Tregs with a pro-inflammatory phenotype, supporting the concept of Treg plasticity in CAD. Our findings provide novel insights into the role of Tregs in CAD and support therapeutic strategies targeting Treg modulation.

Introduction: Clinical evidence suggests that exposure to air pollution particulate matter (PM) is associated with the development of cardiovascular diseases and metabolic disorders. Experimentally, we have shown that exposure to PM induces local and systemic inflammation that involves various innate immune cells and soluble mediators, which leads to visceral obesity and adipose tissue inflammation. In the present study, we aim to expand our understanding of the role of alveolar macrophages in promoting PM-induced inflammation and to further characterize the changes in adipose tissue biology and energy metabolism.

Methods and Results: To evaluate the impact of PM on inflammation and metabolism, male 8-week-old C57BL/6 mice were exposed to a PM surrogate (ROFA, Residual Oil Fly Ash) at 1 mg/kg body weight by intranasal instillation, or to urban air (UA) inside whole-body inhalation chambers located in Buenos Aires City downtown. Inflammatory cell recruitment was evident in the lungs of ROFA-exposed mice, with neutrophils peaking at 6 h post-exposure and macrophages peaking at 72 h. We detected an increase in pro-inflammatory cytokine secretion that was evident in bronchoalveolar lavage fluid (BAL) after PM exposure and sustained in plasma over several days. Bulk RNAseq of sorted alveolar macrophages after PM exposure revealed a proinflammatory gene signature (Cxcl10, Ccl3) and the modulation of several pathways interfering with lipid metabolism. Increased protein levels of these inflammatory mediators were confirmed in BAL and plasma samples. Despite ongoing white adipose tissue (WAT) inflammation and increased plasma catecholamines, we found decreased thermogenic gene expression (Ucp-1, Adrb3) in brown adipose tissue (BAT), suggesting altered thermogenesis. In metabolic chambers, despite enhanced physical activity, ROFA-exposed mice showed significantly reduced heat production. Accordingly, mice breathing UA over 16 weeks showed enhanced weight gain compared to control mice breathing filtered air. Mechanistically, transcriptomic profiling of lung, WAT and BAT showed robust activation of innate inflammatory and tissue‑remodeling pathways in the lung, coupled to repression of thermogenic, mitochondrial and lipid‑oxidation programs in BAT, linking local PM‑induced inflammation to impaired systemic energy expenditure. We also found markers of increased WAT inflammation, altered lipid storage, altered lipid uptake and lipolysis, decrease thermogenesis, defective browning of visceral WAT, and altered levels of circulating adipokines (leptin, adiponectin).

Conclusion: PM exposure alters overall energy metabolism and induces obesity by diminishing the metabolic capacity of BAT, likely as a consequence of local and systemic inflammation.

Background
Pulsed-field ablation (PFA) systems are increasingly being used as single-shot devices for pulmonary vein isolation (PVI) in patients with atrial fibrillation (AF). However, re-do PVIs are typically performed using radiofrequency ablation (RFA) with electroanatomic mapping (EAM) to precisely detect and ablate isolation gaps of the pulmonary veins (PVs). In addition, modification of the atrial substrates e. g. low voltage areas and linear ablations strategies can be performed, if necessary.
The aim of the study was to investigate the acute efficacy, safety and feasibility of re-do PVI using a variable-loop circular catheter (VLCC) with PFA technology and integrated EAM.

Methods
We enrolled 15 consecutive AF patients, who underwent re-do PVI using a VLCC (Varipulse™, J&J) between 03 and 09/2025 (5 paroxysmal and 10 persistent AF).
These patient`s previous PVI had been performed using a cryoballoon (CB) in 13 cases and as surgical epicardial PVI with RFA in 2 cases.
Following PFA of the non-isolated PVs further trigger elimination e. g. isolation of the superior vena cava (SVC) and substrate modifications (posterior box lesion [PBL] or PFA of complex fractionated atrial electrograms [CFAE]) were performed, if necessary. Patients with concomitant typical atrial flutter (Aflut) underwent additional cavo-tricuspid isthmus (CTI) ablation.


Results
In all patients at least one PV was reconnected (median 3 [2-4] reconnected PVs). Successful acute isolation of every reconnected PV was achieved in all of these patients. A median of 9 [5.5-13] PFA applications were required. In 11 patients additional PBL was performed with a median of 7 [5.5-9] PFA applications. In one patient each, a re-do LARA, an ablation of CFAE, and an ablation of atrial tachycardia (AT) (2, 5 and 2 PFA applications, respectively) were performed. Myofibrillar signals of the SVC were ablated in 9 patients with a median of 3 [2-4] applications. Finally, a first and a re-do ablation of the CTI were performed for typical Aflut (7 and 8 applications, respectively). During the first CTI ablation, a switch to an RFA was necessary due to anatomical peculiarities. One patient developed roof-dependent Aflut, which was treated by PBL. In another patient, multiple unstable ATs, that could not be mapped, were terminated by a cardioversion. The median procedure time was 106 [103-120] min, the median fluoroscopy time 9.1 [8.3-10.5] min. No acute complications occurred, especially no phrenic nerve palsies were observed.

Conclusions
Re-do PVI can be performed safely, effectively, and quickly using a VLCC.
Myofibrillar signals in the SVC can be rapidly and effectively eliminated without causing phrenic nerve palsy.
Beyond eliminating triggers for AF, linear ablation concepts for the prevention and termination of typical and atypical Aflut were successfully performed in the majority of cases using the VLCC.
Further studies are needed to confirm these results in larger patient cohorts.

Introduction:
Peripartum cardiomyopathy (PPCM) remains a significant cause of morbidity and mortality worldwide. Recent advancements in understanding the pathophysiology, including the development of a disease-specific therapeutic agent bromocriptine and novelties in heart failure (HF) therapy, have contributed to achieving left ventricular (LV) functional recovery within one year of diagnosis in approximately two-thirds of women with PPCM. However, the underlying mechanisms predicting LV recovery remain poorly understood. We aimed to identify novel circulatory biomarkers that may predict LV recovery in women with PPCM at baseline.

Methods:
We included 34 consecutive women with PPCM for whom data on LV recovery (LVEF ≥ 50% at follow-up) within 12 months was available. We performed serum proteomic profiling using the Olink Target 96 Inflammation, Immuno-Oncology, CVD II and III panels comprising of 368 biomarkers. NPX data were compared between the two groups using t-test. P-values were adjusted for multiple hypothesis testing using the Benjamin-Hochberg method.

Results:
The cohort had a median age of 32.2 years (IQR 25.9-35.6) and presented with a median LVEDD of 59 mm (IQR 55-63) and severely decreased LVEF of 28% (IQR 23-33) with no significant differences between patients who recovered and did not recover their LV function. Within twelve months, 20 of the patients showed persistent LV dysfunction, whereas 14 patients had LV recovery. There were no differences in the prescription of GDMT for HF and Bromocriptine between the two groups (Table 1). BNP (NPX Difference 3.924, p=0.005), NT-proBNP (NPX Difference 3.133, p=0.005), ACE2 (NPX Difference 0.907, p=0.036), TRAIL-R2 (NPX Difference 0.525 p=0.036) and CSF-1 (NPX Difference 0.294, p=0.036) were significantly upregulated in patients with failure to recover LV function compared to those with LV recovery. CXLC5 (NPX Difference -1.907, p=0.036) and MCP-4 (CCL13) (NPX Difference -0.986, p=0.036) were significantly downregulated in PPCM patients with LV non-recovery compared to those with LV recovery at baseline (Figure 1).

Conclusions:
Differences in clinically available biomarkers BNP and NT-proBNP levels were predictive of LV recovery in patients with PPCM. In addition, novel biomarkers have been identified which are hypothesis generating. As such, the downregulation of CCL13, a cytokine involved in the accumulation of leucocytes and CXLC5, a protein involved in neutrophil activation, indicates an ameliorated inflammatory response in patients with PPCM is associated with subsequent LV recovery. The results indicate a potential role of tackling the acute inflammatory and immune response using by targeted immune-modulatory therapy.

Introduction:
Inflammation is increasingly recognized as a key pathophysiological contributor to heart failure with preserved ejection fraction (HFpEF), yet its characterization remains challenging. 18F-FDG PET/CT allows quantitative assessment of inflammatory metabolic activity in the myocardium and systemic immune organs. We aimed to investigate whether myocardial and extra-cardiac 18F-FDG uptake is associated with clinical HFpEF probability, assessed by the HFA-PEFF and H₂FPEF scores, in a cohort undergoing evaluation for suspected sarcoidosis.

Methods:
In this retrospective observational study, 102 patients with preserved left ventricular ejection fraction (≥45%) and clinical sarcoidosis rule-out who underwent 18F-FDG PET/CT were analyzed. Imaging was performed using a standardized fasting and glucose-suppression protocol routinely applied in clinical sarcoidosis PET/CT. Clinical, laboratory, and echocardiographic data were used to calculate HFA-PEFF and H₂FPEF scores. Quantitative PET parameters included myocardial SUVmean, SUVmax, and target-to-background ratio (TBR), as well as splenic and bone-marrow uptake as markers of systemic immune activation. Comparisons were performed between low (0–4) and high (5–7) HFA-PEFF probability groups and across H₂FPEF categories.

Results:
Patients with high HFA-PEFF probability (scores 5–7; n = 28) exhibited significantly increased myocardial 18F-FDG uptake compared with patients with low probability (scores 0–4; n = 73; SUVmean 1.735 ± 0.512 vs. 1.448 ± 0.366; p = 0.010). Stratification by H₂FPEF categories revealed significant global differences in myocardial uptake (SUVmean p = 0.00017; SUV max p < 0.001). Moreover, bone-marrow SUVmax was significantly higher in the intermediate H₂FPEF group compared with the low-risk group (p = 0.021). A similar pattern was observed for splenic SUV max (p = 0.022).

Conclusions:
Higher clinical HFpEF probability, as determined by established diagnostic scores, was associated with increased myocardial 18F-FDG uptake in patients ruled-out for sarcoidosis. Concurrent differences in splenic and bone-marrow uptake support a link between systemic immune activation and HFpEF risk. These findings suggest that 18F-FDG PET/CT may provide a non-invasive, integrative approach to identify inflammatory HFpEF phenotypes.

Fragestellung: Experimentelle Studien am isolierten menschlichen Myocard belegten Kontraktilitätseinbußen und rhythmusrelevante Änderungen des intrazellulären Calciumstoffwechsels nach niederfrequenter Schallexposition.Die Studie prüft, ob unter "real life"-Bedingungen Veränderungen der Herzgesundheit durch niederfrequente Schallexpositionen nachweisbar sind. Die Inzidenz von Herzinsuffizienz und Rhythmusstörungen wurde in zwei Populationen verglichen, in denen eine starke vs. minimale Schallexposition besteht.
Methoden: Es waren zwei Populationen mit jeweils mindestens 18.000 Exponierten gefordert, bei vergleichbaren klimatischen Bedingungen, ethnischer Zusammensetzung, Alters-und Geschlechtsstruktur und sozioökonomischen Parametern. Die Abwesenheit interferierender kardiovaskulärer Noxen musste gegeben sein (Atomkraftwerke, Chemiebetriebe, Fluglärm, Großbaustellen). Es konnten im Kreis Paderborn vier Gemeinden identifiziert werden, die die statistisch geforderten Einschlusskriterien erfüllten.
Ergebnisse: Die Stadt Lichtenau und die Gemeinde Borchen wurden identifiziert als erheblich belastet durch niederfrequente Schallexposition. Die Gemeinden Hövelhof und Delbrück bildeten die expositionsarme Kontrollgruppe. Nach dem Informationsfreiheitsgesetz NRW stellte die KV Westphalen-Lippe die Fallzahlen für Erkrankungen des Herz-Kreislauf-Systems für die genannten Kommunen im Kreis Paderborn zur Verfügung (nach § 5 Abs. 1 Satz 5 IFG NRW). Die ICD-Codes I49 (Rhythmusstörung (bedrohlich)) und I50 & I50.1 (Herzinsuffizienz) wurden für die Kalenderjahre 2021 bis 2024 übermittelt. In Borchen kam es im Vergleich zu Delbrück zu einer signifikanten Steigerung der Inzidenz neu aufgetretener Herzinsuffizienz (p < 0.0001), ebenso in Lichtenau (p < 0.0001). Auf das Jahresmittel bezogen lag die Steigerung in Borchen zwischen 21 % und 53 %, in Lichtenau zwischen 20 % und 68 %. Für Rhythmusstörungen war die Inzidenz ebenfalls in der Verum-Gruppe auf dem Signifikanzniveau von p < 0.0001 deutlich erhöht.
Schlussfolgerungen: Die Daten zeigen ein signifikant erhöhtes kardiovaskuläres Erkrankungsrisiko in Kommunen mit starker Exposition von niederfrequentem Schall. Es sind daher umgehend geeignete Maßnahmen zu ergreifen, um die exponierte Bevölkerung über das Risiko von Rhythmusstörungen und Herzinsuffizient aufzuklären, um zeitnah geeignete therapeutische Maßnahmen ergreifen zu können. Für detaillierte Studien sollten Forschungsmittel bereit gestellt werden, um die Grenzwerte der aufklärungspflichtigen niederfrequenten Schallbelastung exakt zu definieren.

Background:
Current risk stratification algorithms capture high-risk individuals with classical risk factors or established atherosclerotic cardiovascular disease (ASCVD). However, a clinically relevant proportion of individuals without threshold levels of standard modifiable risk factors (SMuRF) – namely hypertension, dyslipidemia, diabetes mellitus and smoking – experience cardiovascular (CV) events. Prompted by genetic data suggesting a causal role of interleukin-6 (IL-6) in the development of ASCVD, we investigated the role of IL-6 in the prediction of CV events in SMuRF-less individuals, to probe pathophysiologic links between low-grade inflammation and ASCVD development.

Methods:
IL-6 was measured in 7,133 SMuRF-less UK Biobank participants with no known history of ASCVD. IL-6 measurements were performed as part of the proteomics substudy. The primary endpoint was a composite of non-fatal myocardial infarction, non-fatal stroke or CV death (MACE, major adverse cardiovascular events).

Results:
During a median follow-up of 13.7 years, MACE occurred in 241 subjects. Those with MACE had higher IL-6 concentrations than event-free subjects (p < 0.001). Kaplan-Meier analyses showed a stepwise increase in MACE across IL-6 tertiles (log-rank p < 0.001). IL-6 was associated with MACE in univariable models (hazard ratio: 2.78; 95% confidence interval: 2.06, 3.73; p < 0.001). After adjustment for age, sex, body mass index, and estimated glomerular filtration rate, SMuRF-less individuals with elevated IL-6 levels had an 81% increased risk of MACE (hazard ratio: 1.81; 95% confidence interval: 1.31, 2.49; p < 0.001). In subgroup analyses, these associations were consistent after stratification by sex and lipoprotein(a) levels.

Conclusion:
This analysis demonstrates a strong link between IL-6 concentrations and CV risk in SMuRF-less individuals. IL-6 predicts long-term risk even in individuals without traditional risk factors who are apparently healthy. These results highlight the importance of residual inflammatory risk in the development of ASCVD and support the rationale for ongoing investigations targeting the IL-6 axis for prevention of heart disease.

Background: Sympathetic overactivity is associated with hepatic steatosis. Renal denervation (RDN) is an approved treatment of uncontrolled hypertension by sympathetic modulation, however its hepatic effects are unknown. This study aimed to assess the effects of RDN on non-invasive tests (NITs) for hepatic steatosis.

Methods: This single-center study included patients with uncontrolled hypertension and cardiometabolic comorbidities undergoing RDN (n=32) or sham procedure (n=10). NITs for hepatic steatosis including the hepatic steatosis index (HSI) and fatty liver index (FLI) were calculated at baseline and follow ups. An external cohort from the UK Biobank was used to validate the correlation between proton density fat fraction (PDFF) MRI scans of the liver and these surrogates.

Results: Compared to the control group, RDN significantly reduced HSI at 3 months (0.4±1.6 vs. -1.3±1.8; p=0.009), 6 months (0.0±2.8 vs. -2.6±3.0; p=0.027) and 12 months (0.0±1.9 vs. -2.1±2.8; p=0.013) as well as FLI at 3 months (2.6±6.9 vs. -3.8±6.9; p=0.021), 6 months (4.2±7.5 vs. -5.7±6.8; p=0.002) and 12 months (2.0±8.7 vs. -6.2±7.1; p=0.018). No significant differences were found in HSI (-1.9±0.7 vs. -2.2±0.7; p=0.77) and FLI (-7.1±1.8 vs. -5.3±1.7; p=0.49) between subjects in the intervention group whose office blood pressure decreased above or below the median of 19.5 mmHg after 12 months. In the UK Biobank, correlation analysis showed a significant relationship between PDFF MRI and HSI (r=0.40; p < 0.0001) and FLI (r=0.27; p < 0.0001).

Conclusions: RDN significantly reduced HSI and FLI in patients with uncontrolled hypertension and cardiometabolic comorbidities suggesting a potential role of sympathetic modulation in metabolic disorders.

Background: While preclinical and early clinical studies suggest the safety and efficacy of sympathetic hepatic denervation (HDN) for blood pressure reduction and metabolic endpoints, detailed anatomical understanding of hepatic perivascular nerves remains scarce.

Aims: To characterize periarterial nerve fibers along the hepatic artery and identify anatomically favorable target regions for catheter-based HDN.

Methods: Hepatic arteries with surrounding tissue were excised from ten human donors and examined histologically. Immunofluorescence staining was used to assess the density and diameter of periarterial nerve fibers.

Results: A total of 13,165 nerves were analyzed. Median nerve fiber size decreased progressively from 93 µm [IQR 54–165] at 1 cm to 72 µm [IQR 48–120] at 7 cm distal to the coeliac trunk (p < 0.001). The largest nerve fibers were located in the posterior and inferior quadrants, each measuring 85 µm [IQR 48–176 and 48–158]. Mean nerve fiber density was significantly higher within the proximal 1–3 cm compared to distal segments 4–7 cm from the coeliac trunk (233±124 vs. 159±76 nerves/cm², p=0.003). Lumen-nerve distance was significantly smaller within the proximal 3 cm compared with distal segments 4–7 cm from the coeliac trunk (2.03 mm [IQR 1.23–3.58] vs. 2.57 mm [IQR 1.26–4.67], p < 0.001). Compared with other quadrants, the shortest lumen–nerve distance was observed in the anterior quadrant (1.75 mm [IQR 1.10–3.22], p < 0.001).

Conclusions: Innervation of especially the proximal hepatic artery is characterized by larger nerve fibers, higher density, and shorter lumen–nerve distances. These findings may guide safe and effective application of HDN in humans.