A 65-year-old man presented with new-onset exertional dyspnea. The predominant abnormality was a marked concentric thickening of the arteriolar walls with strong smooth muscle actin positivity, consistent with small-vessel disease (SVD). This case illustrates a potential mechanism of tachycardia-induced cardiomyopathy (TIC), in which SVD may contribute to impaired myocardial perfusion and reversible left ventricular dysfunction under persistent tachycardia.

BACKGROUND:Early recurrence of atrial tachyarrhythmia (ERAT) during the 90-day blanking period after pulmonary vein isolation (PVI) remains a challenge and has been associated with increased healthcare utilization and patient anxiety. Comparative data on ERAT incidence across energy modalities, including pulsed field ablation (PFA), high-power short-duration (HPSD), very high-power short-duration (vHPSD), and cryoballoon ablation, are limited. OBJECTIVES:To assess and compare the incidence and timing of ERAT following PVI using four ablation technologies. METHODS:In this single-center observational cohort study, 671 consecutive patients undergoing first-time PVI were screened. One hundred consecutive patients undergoing cryoballoon ablation were included as reference group, and three additional groups (HPSD, vHPSD, PFA; each n = 100) were propensity score-matched based on age, sex, BMI, and AF type. ERAT was defined as a clinically detected episode of atrial fibrillation or atrial tachycardia lasting >30 s within 90 days after PVI, documented by 12-lead ECG or Holter monitoring during scheduled or clinically indicated rhythm surveillance. Procedural characteristics, procedural success, and safety were evaluated. RESULTS:Among 400 matched patients, PFA was associated with a significantly lower ERAT incidence compared to thermal ablation (3% vs. 15%-19%, p < 0.01). In PFA patients, ERAT occurred exclusively between Days 31 and 90. Thermal energy groups showed higher rates of early recurrences, often requiring clinical interventions, including hospitalizations and cardioversions. Multivariate analysis did not identify any additional clinical predictors of ERAT. CONCLUSIONS:PFA was associated with a significantly lower rate of early arrhythmias, which may be related to differences in tissue injury mechanisms. These findings suggest PFA may offer a clinical advantage in reducing clinically relevant ERAT and the associated healthcare burden after PVI.

Abstract Atrial fibrillation (AF) is globally the most prevalent arrhythmia for which pulmonary vein isolation (PVI) is an effective intervention. A high comorbidity with mental disorders, in particular depressive and anxiety disorders, is described; however, a systematic synthesis of the existing literature is missing. This systematic review and meta-analysis aim to fill in this gap and to examine the prevalence of depressive and anxiety disorders with in-depth analyses of associated factors and predictors of recurrence of AF. A systematic search in PubMed, Web of Science, Trials, Embase, PsycInfo, and the Cochrane library was conducted. Articles on depressive and anxiety disorders according to the International Classification of Diseases (ICD) or the Diagnostic and Statistical Manual of Mental Disorders (DSM) in English-language in adults with AF undergoing PVI were included. Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines were followed. Prevalence rates were synthesized, and meta-analyses were conducted to calculate the pooled point prevalence of depressive and anxiety disorders applying generalized linear mixed-effects models. Subgroup analyses on the prevalence including the age, sex, AF type, comorbid cardiovascular; meta-correlations and meta-regressions were performed. Predictors of recurrence of AF were calculated using logistic regressions. Eighteen studies with a total of 9,691 observations for depressive disorders and 8,855 observations for anxiety disorders were included. The meta-analyses revealed an overall point prevalence of 20.10% [95% Confidence interval (CI): 13.31% to 29.18%] for depressive disorders and 25.18% [95% CI: 11.71% to 46.08%] for anxiety disorders in patients undergoing PVI. Subgroup analyses indicated higher prevalence rates of depressive disorders in younger patients, those with paroxysmal AF, and patients with comorbid conditions such as heart failure, diabetes, hypertension. Older patients and those with cardiovascular disorders showed a higher prevalence of anxiety disorder. The correlation between pre- and post-PVI mental health status was strong (r = .99 for depression), but neither pre-ablation depression (OR = 1.022, p = .638) nor anxiety (OR = 1.003, p = 0.830) significantly predicted AF recurrence. Meta-regression analyses did not identify significant moderators explaining existing between-study heterogeneity. Depressive and anxiety disorders are highly prevalent among patients with AF undergoing PVI, particularly with higher rates of depression in younger individuals, those with paroxysmal AF, and patients with comorbid cardiovascular conditions. While mental health status improved post-PVI, neither pre-ablation depression nor anxiety were significant predictors of AF recurrence. This suggests that mental health diagnostics and interventions should be integrated into routine care, although they may not directly impact AF recurrence after PVI. Current guidelines address the management of the psychosocial dimension and comorbid mental disorders of AF insufficiently, indicating an unmet need for structured psychosomatic co-management within an interdisciplinary, patient-centered care framework. Following a biopsychosocial approach may be beneficial and warrants further targeted investigation in AF populations.

BACKGROUND:Risk stratification in non-ischemic cardiomyopathies (NICM) remains challenging despite guideline-based phenotypic classification using multimodal diagnostics including endomyocardial biopsy (EMB). We aimed to identify EMB-derived histological and molecular markers that improve phenotypic characterization and long-term risk stratification in patients with NICM. METHODS:In this prospective cohort study, 703 consecutive patients with symptomatic NICM underwent standardized multimodal evaluation, including clinical assessment, cardiac imaging, and endomyocardial biopsy. Biopsy specimens were analyzed using histology, immunohistochemistry, and targeted myocardial mRNA profiling. Associations between endomyocardial markers, and fibroinflammatory remodeling, imaging parameters, and molecular signatures were assessed cross-sectionally. Long-term prognostic relevance was evaluated using survival and multivariable prediction analyses during follow-up of up to fifteen years for all-cause mortality, cardiovascular mortality, implantable cardioverter-defibrillator (ICD) implantation, and appropriate ICD discharge. RESULTS:Elevated myocardial Gremlin-1 expression was associated with increased fibrosis, adverse cardiac remodelling, reduced left ventricular function, and enrichment of pro-fibrotic and inflammatory mRNA signalling pathways. Myocardial and circulating Gremlin-1 expression was independently associated with all-cause and cardiovascular mortality, and ICD implantation and discharge. Machine learning-based phenotyping using histological EMB data identified Gremlin-1 as a key predictive feature of poor prognosis. Incorporation of Gremlin-1 into predictive models significantly improved long-term cardiovascular risk stratification in NICM patients. CONCLUSION:Our results unveil that Gremlin-1 is associated with inflammation and cardiac remodelling in patients with NICM, and patients with Gremlin-1+ EMB and high plasmatic Gremlin-1 concentrations are at elevated risk to develop adverse cardiovascular events. Thus, the histological evaluation of Gremlin-1 may help to improve risk discrimination and management of NICM and HF patients.

Redo ablation procedures are frequently required in patients with recurrent atrial fibrillation (AF) and atypical atrial flutter following initial pulmonary vein isolation (PVI). While focal pulsed-field ablation (PFA) has emerged as a promising nonthermal alternative, data on its long-term efficacy and safety in redo procedures remain limited. This study evaluates the 1-year outcomes of focal PFA in redo ablations for AF and atypical flutter, focusing on arrhythmia recurrence, procedural success, and safety. A retrospective analysis was conducted on 54 patients undergoing redo ablation with focal PFA at a single center. Procedural endpoints included acute and chronic procedural success, additional ablation line integrity, and complication rates. Arrhythmia recurrence was assessed via ECG and 24-h Holter monitoring at 6 and 12 months. Complete PVI and bidirectional block of all additional ablation lines were confirmed in all cases at the end of the procedure. During the 1-year follow-up, 29.63

BACKGROUND:The impact of tricuspid regurgitation (TR) on the outcomes of pulmonary vein isolation (PVI) for atrial fibrillation (AF) remains unclear. While the effects of mitral regurgitation (MR) on PVI outcomes are well-documented, there are limited data on how moderate or greater TR influences PVI efficacy and recurrence rates. OBJECTIVES:The aim of this study was to assess the impact of moderate or greater TR on the outcomes of PVI, particularly focusing on AF recurrence rates within the first year post-PVI. METHODS:We conducted an observational cohort study involving 421 patients undergoing their first PVI. 96 patients with moderate or greater TR were propensity score-matched with 96 controls based on age, sex, body mass index, and MR severity. Procedural parameters, complication rates, and AF recurrence within 1-year post-PVI were analyzed. RESULTS:Despite comparable procedural parameters and low overall complication rates between the groups, patients with moderate or greater TR experienced significantly higher AF recurrence rates within the first year after PVI. Right atrium (RA) area was notably larger in these patients, suggesting a potential link between RA remodeling and increased AF recurrence. CONCLUSIONS:Our findings indicate that moderate or greater TR is associated with higher recurrence rates of AF after PVI, potentially due to RA enlargement and remodeling. This highlights the need for tailored ablation strategies that consider the RA substrate and/or TR treatment in patients with significant TR and AF. Further multicenter, prospective studies are required to validate these results and explore long-term outcomes.

Background Acute pulmonary embolism (PE) is a life-threatening situation. While anticoagulation should be initiated without any delay in all patients with an intermediate or high clinical probability of PE, individual acute phase treatment in patients with intermediate or intermediate-high-risk PE still can be optimized.Case summary An 82-year-old female patient was referred to our emergency department after experiencing syncope and acute onset of shortness of breath. Computed tomography (CT) of the chest showed central and extensive peripheral PE. Echocardiography additionally revealed a massive and highly mobile clot-in-transit located in the right atrium (RA). Given the size and mobility of the clot-in-transit, we chose to perform an off-label mechanical thrombectomy. Due to repeated PE with progressive right ventricular (RV) failure and high peripheral thrombus burden, we decided to perform low-dose systemic lysis. After 24 h, she showed significant clinical improvement and was discharged later with recovered RV function and dimensions.Discussion In that case, acute PE was complicated by the presence of a large clot-in-transit in the RA. Initially, there was no indication for mechanical thrombectomy or systemic lysis for the patient's intermediate to high-risk PE. The risk of embolization of the very large clot-in-transit prompted us to remove the mobile thrombus mechanically. When the repeated PE resulted in an increase in afterload and progressive right heart failure, we decided to perform low-dose systemic lysis. The off-label use of the FlowTriever (R) prevented the impending embolization of the 14 cm long thrombus from the RA into the pulmonary circulation. In this case, lysis also appears to make sense, particularly given the high peripheral thrombus burden.

Atrial fibrillation (AF) is the most common heart rhythm disorder worldwide. As treatment methods evolve, optimizing personalized therapy based on patient characteristics, such as sex, becomes crucial. This study investigates sex differences in high-power short-duration (HPSD) pulmonary vein isolation (PVI) in overweight and obese patients. We analyzed data from 189 overweight and obese patients who underwent HPSD PVI for AF, comparing demographic information, procedural details, outcomes, and complications between male and female patients. Our analysis revealed fewer women underwent PVI compared to men, with women typically older and showing more pronounced changes in the left atrial substrate. Despite these differences, the safety and efficacy of PVI were comparable between sexes, including in the BMI >= 30 kg/m2 subgroup and after age adjustment. The findings emphasize the need for early AF screening in women to prevent treatment delays and show that considering sex-specific differences in fat distribution can improve procedural outcomes. These insights support the need for tailored management strategies for AF in overweight and obese populations, addressing sex-specific risks and anatomical variations.

Aims Cyclophilin A (CyPA) induces leucocyte recruitment and platelet activation upon release into the extracellular space. Extracellular CyPA therefore plays a critical role in immuno-inflammatory responses in tissue injury and thrombosis upon platelet activation. To date, CD147 (EMMPRIN) has been described as the primary receptor mediating extracellular effects of CyPA in platelets and leucocytes. The receptor for advanced glycation end products (RAGE) shares inflammatory and prothrombotic properties and has also been found to have similar ligands as CD147. In this study, we investigated the role of RAGE as a previously unknown interaction partner for CyPA.Methods and results Confocal imaging, proximity ligation, co-immunoprecipitation, and atomic force microscopy were performed and demonstrated an interaction of CyPA with RAGE on the cell surface. Static and dynamic cell adhesion and chemotaxis assays towards extracellular CyPA using human leucocytes and leucocytes from RAGE-deficient Ager-/- mice were conducted. Inhibition of RAGE abrogated CyPA-induced effects on leucocyte adhesion and chemotaxis in vitro. Accordingly, Ager-/- mice showed reduced leucocyte recruitment and endothelial adhesion towards CyPA in vivo. In wild-type mice, we observed a downregulation of RAGE on leucocytes when endogenous extracellular CyPA was reduced. We furthermore evaluated the role of RAGE for platelet activation and thrombus formation upon CyPA stimulation. CyPA-induced activation of platelets was found to be dependent on RAGE, as inhibition of RAGE, as well as platelets from Ager-/- mice showed a diminished activation and thrombus formation upon CyPA stimulation. CyPA-induced signalling through RAGE was found to involve central signalling pathways including the adaptor protein MyD88, intracellular Ca2+ signalling, and NF-kappa B activation.Conclusion We propose RAGE as a hitherto unknown receptor for CyPA mediating leucocyte as well as platelet activation. The CyPA-RAGE interaction thus represents a novel mechanism in thrombo-inflammation. Graphical Abstract RAGE is a novel receptor for extracellular CyPA on leucocytes and platelets. RAGE was found to interact with CyPA and to play an important role in CyPA-induced leucocyte and platelet functions. Platelet activation, coaggregate formation, and intracellular Ca2+ release by CyPA were abrogated when RAGE was absent or blocked. Similarly, CyPA-induced leucocyte migration and adhesion were found to be dependent on RAGE in vivo and in vitro. CyPA abundance was furthermore identified to regulate RAGE expression in vivo.

BACKGROUND:Cardiac hypertrophy is characterized by remodeling of the myocardium, which involves alterations in the ECM (extracellular matrix) and cardiomyocyte structure. These alterations critically contribute to impaired contractility and relaxation, ultimately leading to heart failure. Emerging evidence implicates that extracellular signaling molecules are critically involved in the pathogenesis of cardiac hypertrophy and remodeling. The immunophilin CyPA (cyclophilin A) has been identified as a potential culprit. In this study, we aimed to unravel the interplay between eCyPA (extracellular CyPA) and myocardial dysfunction and evaluate the therapeutic potential of inhibiting its extracellular accumulation to improve heart function.METHODS:Employing a multidisciplinary approach encompassing in silico, in vitro, in vivo, and ex vivo experiments we studied a mouse model of cardiac hypertrophy and human heart specimen to decipher the interaction of CyPA and the cardiac microenvironment in highly relevant pre-/clinical settings. Myocardial expression of CyPA (immunohistology) and the inflammatory transcriptome (NanoString) was analyzed in human cardiac tissue derived from patients with nonischemic, noninflammatory congestive heart failure (n=187). These analyses were paralleled by a mouse model of Ang (angiotensin) II-induced heart failure, which was assessed by functional (echocardiography), structural (immunohistology, atomic force microscopy), and biomolecular (Raman spectroscopy) analyses. The effect of inhibiting eCyPA in the cardiac microenvironment was evaluated using a newly developed neutralizing anti-eCyPA monoclonal antibody.RESULTS:We observed a significant accumulation of eCyPA in both human and murine-failing hearts. Importantly, higher eCyPA expression was associated with poor clinical outcomes in patients (P=0.043) and contractile dysfunction in mice (Pearson correlation coefficient, -0.73). Further, myocardial expression of eCyPA was critically associated with an increase in myocardial hypertrophy, inflammation, fibrosis, stiffness, and cardiac dysfunction in vivo. Antibody-based inhibition of eCyPA prevented (Ang II)-induced myocardial remodeling and dysfunction in mice.CONCLUSIONS:Our study provides strong evidence of the pathogenic role of eCyPA in remodeling, myocardial stiffening, and dysfunction in heart failure. The findings suggest that antibody-based inhibition of eCyPA may offer a novel therapeutic strategy for nonischemic heart failure. Further research is needed to evaluate the translational potential of these interventions in human patients with cardiac hypertrophy.

Focal pulsed field ablation (PFA) is a novel technique for treating cardiac arrhythmias. It has demonstrated positive results in initial studies and has a good safety profile. In recent studies, PFA was often utilized for first-time pulmonary vein isolation (PVI) and was performed under general anesthesia. In our study, we assessed the feasibility, safety, acute procedural efficacy, and efficiency of focal PFA under deep sedation in patients, 80% of whom had undergone at least one left atrial ablation previously. We treated 30 patients (71 ± 7, 46% male) using the CENTAURI system for various atrial arrhythmias, including atrial fibrillation, typical and atypical atrial flutter, and focal atrial tachycardia. The average procedure and fluoroscopy times were 122 ± 43 min and 9 ± 7 min, respectively. A total of 83.33% of patients received additional line ablations beyond PVI, specifically targeting the posterior box and anterior mitral line. All ablations were successfully performed in deep sedation with only one major and one minor complication observed. The major complication was a vasospasm of the right coronary artery during ablation of the cavotricuspid isthmus, which was treated successfully with intracoronary nitroglycerin. All patients could be discharged in sinus rhythm. Moreover, adenosine appears effective in identifying dormant conduction in some patients after focal PFA. In conclusion, focal PFA is an effective approach for complex left atrial ablations under deep sedation, offering both high efficacy and efficiency with a reliable safety profile. Studies on long-term outcomes are needed.

Aim Data on associations of invasively determined hemodynamic parameters with procedural success and outcomes in patients suffering from mitral regurgitation (MR) undergoing transcatheter edge-to-edge repair of the mitral valve (M-TEER) is limited.Methods and results We enrolled 239 patients with symptomatic MR of grade 2 + , who received M-TEER. All patients underwent extensive pre-interventional invasive hemodynamic measurements via right heart catheterization (mean pulmonary arterial pressure (mPAP), systolic- (PAPsys) and diastolic pulmonary arterial pressure (PAPdia), pulmonary arterial wedge pressure (PAWP), a-wave, v-wave, pulmonary vascular resistance (PVR), transpulmonary pressure gradient (TPG), cardiac index (CI), stroke volume index (SVI)). mPAP and PAWP at baseline were neither associated with procedural success, immediate reduction of MR, nor residual MR after 6 months of follow-up. The composite outcome (All-cause mortality (ACM) and/or heart failure induced rehospitalization (HFH)) and HFH differed significantly after M-TEER when stratified according to mPAP, PAWP, PAPdia, a-wave and v-wave. ACM was not associated with the afore mentioned parameters. Neither PVR, TPG, CI nor SVI were associated with the composite outcome and HFH, respectively. In multivariable analyses, PAWP was independently associated with the composite outcome and HFH. PVR and SVI were not associated with outcomes.Conclusion PAWP at baseline was significantly and independently associated with HFH and might serve as a valuable parameter for identifying patients at high risk for HFH after M-TEER. ACM and procedural success were not affected by pulmonary arterial pressure before M-TEER. We suggest that the post-capillary component of PH serves as the driving force behind the risk of HFH.

Als Tachykardiomyopathie (TMP) bezeichnet man die Ausbildung einer Herzinsuffizienz aufgrund einer Herzrhythmusstörung – ausgelöst durch schnelle und/oder unregelmäßige Kammeraktionen. Die TMP ist eine prinzipiell (zumindest teilweise) reversible Erkrankung, sodass der Kontrolle der Arrhythmie eine zentrale Bedeutung zukommt.