Atrial fibrillation is the most prevalent sustained cardiac arrhythmia, characterized by limited therapeutic options because of incompletely understood mechanisms of its development. The key underlying pathogenetic mechanisms involve atrial myocardial inflammation and fibrosis in response to pressure or volume overload, myocardial infarction, as well as metabolic alterations. Recent studies have highlighted the crucial role of osteopontin in diverse cardiovascular diseases, including atrial fibrillation. Osteopontin is a multifunctional extracellular matrix protein that has recently emerged as a potential mediator of atrial remodeling and arrhythmogenesis. Human studies have revealed that circulating osteopontin levels can serve as a valuable biomarker for atrial fibrillation and its progression. Furthermore, in vitro studies have demonstrated that osteopontin modulates several key cellular processes involved in atrial inflammation and fibrosis, including fibroblast activation, extracellular matrix remodeling, and proinflammatory cytokine production. This review critically examines the available evidence on the role of osteopontin in atrial remodeling and arrhythmia starting from the molecular mechanisms by which osteopontin contributes to structural and electrical remodeling of the atria, to its potential as a biomarker for atrial fibrillation.

Background and aims:Cryoballoon ablation of atrial fibrillation alters a significant amount of vital myocardium contributing to its electrical activity. However, the effect of pulmonary vein isolation (PVI) on the P-wave is unclear. The study aimed to quantify P-wave changes following individual PVI using signal-averaged ECG analysis. Materials and methods:Unfiltered high-resolution (2,000 samples/second) ECGs were obtained for 5 min pre- and post-isolation of each pulmonary vein in 69 participants using 12 standard and 10 additional leads optimized for atrial electrical activity detection. Signal-averaged ECGs were computed and analyzed using custom software in Matlab. This study was registered at ClinicalTrials.gov (Identifier: NCT06061120). Results:Significant changes in ECG parameters were found. Following complete PVI, P-wave terminal force measured in lead V1 (3.08 ± 1.99 vs. 2.63 ± 1.76 mV*ms, p = 0.003), as well as P-wave complexity (2.05 ± 0.65 vs. 1.79 ± 0.51, p < 0.001) and sample entropy (0.210 ± 0.039 vs. 0.187 ± 0.028 au, p < 0.001), both averaged across all leads, decreased significantly. Ablation of the left pulmonary veins was associated with lower values in P-wave terminal force (3.07 ± 2.05 vs. 2.84 ± 1.88 mV*ms, p = 0.003), P-wave complexity (2.02 ± 0.64 vs. 1.90 ± 0.57, p = 0.003), and sample entropy (0.210 ± 0.039 vs. 0.197 ± 0.031 au, p < 0.001) after ablation. For ablation of the right pulmonary veins, a decline was observed in sample entropy (0.196 ± 0.031 vs. 0.190 ± 0.027 au, p = 0.046). Conclusion:The observed changes in signal-averaged P-wave parameters during cryoballoon PVI may indicate acute intraprocedural effects on atrial electrophysiology. These exploratory findings suggest that high-resolution, non-invasive ECG recordings are capable to detect stepwise changes of electrical atrial activity, offering new perspectives for intraprocedural assessment of ablation effects.

BACKGROUND:Data on premature ventricular complex (PVC) burden after pulmonary vein isolation (PVI) for atrial fibrillation (AF) are inconsistent and often limited to selected populations. METHODS:We retrospectively analyzed patients undergoing successful first-time PVI for paroxysmal or persistent AF between January 2019 and June 2023. PVC burden was quantified by long-term ECG at baseline, 3 months, and 12 months. Ablation energy sources included cryoballoon, radiofrequency, and pulsed field ablation. RESULTS:Among 1,069 patients, median PVC burden decreased from 6.82/h at baseline to 1.44/h at 3 months and 3.75/h at 12 months. In patients with complete follow-up (n = 165), PVC burden declined significantly overall (Friedman test p < 0.001). Post-hoc analyses confirmed reductions from baseline to 3 and 12 months, with a modest increase between 3 and 12 months (all p < 0.01). PVC burden was similar regardless of AF recurrence or ablation energy. At 12 months, 4.6% of patients had high PVC burden (> 5%). Diabetes mellitus (OR = 4.43; 95% CI: 1.49-13.17; p = 0.007) and reduced left ventricular ejection fraction (OR = 6.36; 95% CI: 2.03-19.91; p = 0.002) were independently associated with elevated burden, while other covariates were not significant. CONCLUSION:PVI significantly reduces PVC burden in most patients, independent of AF recurrence or ablation modality. Diabetes and impaired ventricular function identify patients at risk of persistent high PVC burden. PVI may particularly benefit AF patients with symptomatic PVCs, but larger prospective studies are needed to validate these findings and assess clinical outcomes.

Atrial fibrillation is a prevalent cardiac arrhythmia, significantly increasing the risk of stroke, heart failure, and mortality. Early detection, especially during asymptomatic and paroxysmal stages, is essential for effective intervention. This study explores the application of deep neural networks in simplified ECG screening to enhance population-wide detection of atrial fibrillation. A handheld device, MyDiagnostick, was employed for large-scale ECG data acquisition within a pharmacy-based clinical trial on 7295 subjects aged 65 years and older. Automated diagnosis yielded 6.08% of AF prevalence in the given dataset. The data were then analyzed using a validated deep neural network model for the detection of cardiac arrhythmia in 12-lead ECG data for feature extraction and detection of atrial fibrillation. In addition, we investigate the capabilities of explainable artificial intelligence to provide diagnostic support for cardiologists and assess the feasibility of implementing deep neural networks in wearable devices for continuous monitoring. The study also emphasizes the importance of interpretability in artificial intelligence models for medical applications, leveraging explainable artificial intelligence to highlight ECG segments indicative of atrial fibrillation. Our findings demonstrate the efficacy of deep neural networks in atrial fibrillation detection with an F1-score of 86% vs. 81% of the automated ECG stick analysis and the potential for their integration into wearable technology by successfully reducing the number of weights by 99% without significant loss of accuracy, providing a robust tool for early diagnosis and continuous monitoring of atrial fibrillation.

Background Atrial fibrillation (AF) is the most common cardiac arrhythmia with a massive burden on global health. The prevalence of AF increases dramatically with age and can be up to 18% in patients older than 80 years. Telomeres, which are short, repeated DNA sequences at the end of chromosomes, are known to act as a biological aging marker. In this study, we investigated the relation of telomere shortening and AF in the context of atrial remodeling. Furthermore, we assessed changes in the gene expression profiles of patients with AF according to telomere length (TL) and left atrial fibrosis. Methods We included 72 patients undergoing catheter ablation for AF. Bipolar voltage maps were obtained to determine left atrial low voltage areas as a surrogate for atrial fibrosis. TL was quantified and correlated to low voltage areas. 3′ mRNA sequencing was performed for gene expression profiling. Clonal hematopoiesis of indeterminate potential was assessed by next generation sequencing. Telomerase reverse transcriptase knockout (Tert−/−) and telomerase RNA component knockout (Terc−/−) mice were used to investigate the mechanistic impact of telomere shortening on atrial remodeling. Results Patients with advanced left atrial fibrosis had shorter telomeres compared with patients with healthy left atria. Furthermore, there was a strong correlation between the extent of left atrial low voltage areas, TL, and outcome after catheter ablation of AF. 24 months after ablation, only 26.5% of patients with advanced fibrosis and short TL were in sinus rhythm compared with 62.5% of patients with no/low fibrosis and long TL. Gene expression profiles and clonal hematopoiesis of indeterminate potential frequency differed in patients with AF with short and long telomeres. Finally, atrial tissue of mouse models with shortened telomeres showed marked left atrial fibrosis and over‐expression of fibrosis‐related genes. Conclusions Telomere shortening is correlated with left atrial remodeling. Shorter telomeres are associated with a series of molecular events which could eventually lead to cardiac fibrosis and perpetuate AF.

Pulsed field ablation (PFA) is an emerging technology for the treatment of atrial fibrillation (AF), for which pre-clinical and early-stage clinical data are suggestive of some degree of preferentiality to myocardial tissue ablation without damage to adjacent structures. Here in the MANIFEST-17K study we assessed the safety of PFA by studying the post-approval use of this treatment modality. Of the 116 centers performing post-approval PFA with a pentaspline catheter, data were received from 106 centers (91.4% participation) regarding 17,642 patients undergoing PFA (mean age 64, 34.7% female, 57.8% paroxysmal AF and 35.2% persistent AF). No esophageal complications, pulmonary vein stenosis or persistent phrenic palsy was reported (transient palsy was reported in 0.06% of patients; 11 of 17,642). Major complications, reported for similar to 1% of patients (173 of 17,642), were pericardial tamponade (0.36%; 63 of 17,642) and vascular events (0.30%; 53 of 17,642). Stroke was rare (0.12%; 22 of 17,642) and death was even rarer (0.03%; 5 of 17,642). Unexpected complications of PFA were coronary arterial spasm in 0.14% of patients (25 of 17,642) and hemolysis-related acute renal failure necessitating hemodialysis in 0.03% of patients (5 of 17,642). Taken together, these data indicate that PFA demonstrates a favorable safety profile by avoiding much of the collateral damage seen with conventional thermal ablation. PFA has the potential to be transformative for the management of patients with AF.

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.

BackgroundAtrial fibrosis represents a major hallmark in disease progression of atrial fibrillation (AF). We have previously shown that circulating microRNA-21 (miR-21) correlates with the extent of left atrial fibrosis in patients undergoing catheter ablation for AF and can serve as a biomarker to predict ablation success. In this study, we aimed to validate the role of miR-21-5p as a biomarker in a large cohort of AF patients and to investigate its pathophysiological role in atrial remodeling.MethodsFor the validation cohort, we included 175 patients undergoing catheter ablation for AF. Bipolar voltage maps were obtained, circulating miR-21-5p was measured, and patients were followed-up for 12 months including ECG holter monitoring. AF was simulated by tachyarrhythmic pacing of cultured cardiomyocytes, the culture medium was transferred to fibroblast, and fibrosis pathways were analysed.Results73.3% of patients with no/minor LVAs, 51.4% of patients with moderate LVAs and only 18.2% of patients with extensive LVAs were in stable sinus rhythm (SR) 12 months after ablation (p < 0.01). Circulating miR-21-5p levels significantly correlated with the extent of LVAs and event-free survival. In-vitro tachyarrhythmic pacing of HL-1 cardiomyocytes resulted in an increased miR-21-5p expression. Transfer of the culture medium to fibroblasts induced fibrosis pathways and collagen production. The HDAC1 inhibitor mocetinostat was found to inhibit atrial fibrosis development.ConclusionWe validated miR-21-5p as a biomarker that reflects the extent of left atrial fibrosis in AF patients. Furthermore, we found that miR-21-5p is released in-vitro from cardiomyocytes under tachyarrhythmic conditions and stimulates fibroblasts in a paracrine mode to induce collagen production.

Atrial fibrillation (AF) is an arrhythmic cardiac disorder with a high and increasing prevalence in aging societies, which is associated with a risk for stroke and heart failure. However, early detection of onset AF can become cumbersome since it often manifests in an asymptomatic and paroxysmal nature, also known as silent AF. Large-scale screenings can help identifying silent AF and allow for early treatment to prevent more severe implications. In this work, we present a machine learning-based algorithm for assessing signal quality of hand-held diagnostic ECG devices to prevent misclassification due to insufficient signal quality. A large-scale community pharmacy-based screening study was conducted on 7295 older subjects to investigate the performance of a single-lead ECG device to detect silent AF. Classification (normal sinus rhythm or AF) of the ECG recordings was initially performed automatically by an internal on-chip algorithm. The signal quality of each recording was assessed by clinical experts and used as a reference for the training process. Signal processing stages were explicitly adapted to the individual electrode characteristics of the ECG device since its recordings differ from conventional ECG tracings. With respect to the clinical expert ratings, the artificial intelligence-based signal quality assessment (AISQA) index yielded strong correlation of 0.75 during validation and high correlation of 0.60 during testing. Our results suggest that large-scale screenings of older subjects would greatly benefit from an automated signal quality assessment to repeat measurements if applicable, suggest additional human overread and reduce automated misclassifications.

Als supraventrikuläre Tachykardien bezeichnet man schnelle Herzrhythmusstörungen, die in den Vorhöfen entstehen. In der Regel imponieren sie im EKG als Schmalkomplextachykardie, können jedoch unter bestimmten Umständen (vorbestehendes Blockbild, Aberranz, akzessorisches Leitungsbündel) auch als Breitkomplextachykardie in Erscheinung treten. Unterschieden werden Tachykardien mit Reentrymechanismus von solchen mit abnormer Automatie oder getriggerter Aktivität. Da für die meisten supraventrikulären Tachykardien (SVTs) mit einer Katheterablation eine kurative Behandlungsoption mit geringen Risiken besteht, sollte diese großzügig empfohlen werden. Die häufigste supraventrikuläre Tachykardie ist das Vorhofflimmern, dessen Prävalenz ein endemisches Ausmaß angenommen hat und mit einer erheblichen Morbidität und Mortalität vergesellschaftet ist. Vorhofflimmern ist ein komplexes Krankheitsbild, sodass eine ausführliche Charakterisierung dieser Patienten erforderlich ist. Die Therapieplanung umfasst die Schlaganfallprophylaxe, die Symptomenkontrolle und die Behandlung der Komorbiditäten.

Tachycardiomyopathy (TMP) is the development of heart failure due to a cardiac arrhythmia - triggered by rapid and/or irregular ventricular actions. TMP is in principle a (at least partially) reversible disease, so that control of the arrhythmia is of central importance. This article provides an overview of the causes, diagnosis and therapy.

Background:Cryoballoon ablation is a first-line therapy for atrial fibrillation. We compared the efficacy and safety of two ablation systems and addressed the influence of pulmonary vein (PV) anatomy on performance and outcome. Methods:We consecutively enrolled 122 patients who were planned for first-time cryoballoon ablation. Patients were assigned 1:1 for ablation with the POLARx or the Arctic Front Advance Pro (AFAP) system and followed-up for 12 months. Procedural parameters were recorded during the ablation. Before the procedure, a magnetic resonance angiography (MRA) of the PVs was generated and diameter, area, and shape of each PV ostium were assessed. We applied an evaluated PV anatomical scoring system on our MRA measurement data ranging from 0 (best anatomical combination) to 5. Results:Procedures performed with POLARx were associated with shorter time to balloon temperature -30°C (p < .001), lower balloon nadir temperature (p < .001), and longer thawing time till 0°C (p < .001) in all PVs, however, time to isolation was similar. We observed a decreasing performance with each increase in the score for the AFAP, whereas the POLARx performed constant regardless of the score. At 1 year, AF recurred in 14 of 44 patients treated with AFAP (31.8%) and in 10 of 45 patients treated with POLARx (22.2%) (hazard ratio, 0.61; 95% CI 0.28 to 1.37; p = .225). There was no significant correlation between PV anatomy and clinical outcome. Conclusion:We found significant differences in cooling kinetics, especially when anatomical conditions are difficult. However, both systems have a comparable outcome and safety profile.

Background: Mutations in the Lamin A/C (LMNA) gene are responsible for about 6% of all familial dilated cardiomyopathy (DCM) cases which tend to present at a young age and follow a fulminant course. Methods: We report a 47-year-old DCM patient with severely impaired left ventricular ejection fraction and NYHA functional class IV despite optimal heart failure treatment. Whole-exome sequencing revealed an LMNA E161K missense mutation as the pathogenetic cause for DCM in this patient. We generated a patient-specific LMNA-knock in (LMNA-KI) in vitro model using mES cells. Results: Beta adrenergic stimulation of cardiomyocytes derived from LMNA-KI mES cells resulted in augmented mTOR signaling and increased dysregulation of action potentials, which could be effectively prevented by the mTOR-inhibitor rapamycin. A cardiac biopsy confirmed strong activation of the mTOR-signaling pathway in the patient. An off-label treatment with oral rapamycin was initiated and resulted in an improvement in left ventricular ejection fraction (27.8% to 44.5%), NT-BNP (8120 ng/L to 2210 ng/L) and NYHA functional class. Conclusion: We have successfully generated the first in vitro model to recapitulate a patient-specific LMNA E161K mutation which leads to a severe form of DCM. The model may serve as a template for individualized and specific treatment of heart failure.

Die Erfassung biologischer Signale im Alltag durch Wearables ist durch den technischen Fortschritt und die breite Verfügbarkeit allgegenwärtig. Gezielt oder nebenbei ermöglichen zahlreiche Geräte die Erkennung von Herzrhythmusstörungen. Dieser Artikel gibt einen Überblick über den medizinischen Hintergrund, verfügbare Technologien, Konsequenzen aus der Detektion von Vorhofflimmern und die sich damit ergebenden Möglichkeiten und Limitationen.

Die neuen Leitlinien der ESC zur Diagnose und Behandlung von Vorhofflimmern setzen die vorhandenen Evidenzen aus den Ergebnissen klinischer Studien in eine klare Perspektive zur klinischen Anwendung um. Deutlich wird der generelle Trend zu einer intensiveren individuellen und personalisierten Betrachtung der Patienten mit Vorhofflimmern insbesondere in 2 Bereichen: durch die Einführung der Charakterisierung von Vorhofflimmern mit dem 4S-Schema (Einbeziehung von Schlaganfallrisiko, Symptome, Vorhofflimmerlast, Substrat) als präzisere Methode im Vergleich zur seit vielen Jahren gelebten „PPP“-Klassifizierung (paroxysmal, persistierend, permanent). Dieser Zugang wird auch in den Ablationsempfehlungen sichtbar, in denen geraten wird, die Rezidivrisiken für das Wiederauftreten von Vorhofflimmern nach einer Ablationsbehandlung bereits vor der Intervention intensiv mit in die Überlegungen einzubeziehen. Wie schon in den 2016 ESC-Leitlinien wird die integrierte Behandlung von Patienten mit Vorhofflimmern betont und mit dem ABC-Behandlungspfad ein einfacher und intuitiver Weg aufgezeigt, um die wesentlichen Behandlungsschritte klar darzustellen: A für „anticoagulation/avoid stroke“, B für „better symptoms“, und C für „comorbidities“. Außerdem werden erstmalig Empfehlungen für Qualitätsindikatoren und für Behandlungsbewertungen durch Patienten (sog. PROs = „patient reported outcomes“) vorgestellt. Im Bereich der Antikoagulation zur Schlaganfallprävention stärken die Leitlinien den Einsatz der Nicht-Vitamin-K-Antikoagulanzien entsprechend dem individuellen Schlaganfallrisiko nach CHA2DS2-VASc, empfehlen aber auch die intensivere Beachtung der Blutungsrisiken. Aufgrund fehlender neuer Studiendaten gibt es keine Änderung der Empfehlungen für den interventionellen Vorhofohrverschluss – es bleibt bei IIb („kann erwogen werden“). Im Bereich der frequenzregularisierenden Behandlung bleiben Kalziumantagonisten und Betablocker ggf. in Kombination mit Digitalis die erste Wahl. In der Rhythmuskontrolle findet sich für den Bereich der medikamentösen Therapie eine nachvollziehbare Abwertung für Sotalol aufgrund der bekannten Behandlungsrisiken. Die kurz nach Veröffentlichung der Leitlinien vorgestellte EAST-Studie wird im Hinblick auf die Bedeutung einer antiarrhythmischen Therapie in diesem Kommentar besonders diskutiert. Aufgewertet wird die Katheterablation von Vorhofflimmern in den Leitlinien insbesondere für Patienten mit Tachykardie-induzierter schwerer Herzinsuffizienz (IB-Empfehlung), aber auch für Patienten mit Vorhofflimmern und HFrEF bei strukturellen Herzerkrankungen (IIa-Empfehlung).

Das Langzeit-EKG stellt einen wichtigen Baustein in der kardiologischen Diagnostik dar. Es dient heutzutage hauptsächlich dazu, Herzrhythmusstörungen zu entdecken, die nur intermittierend auftreten und deshalb im normalen 12-Kanal-EKG möglicherweise nicht zu erfassen sind. Hilfreich ist es, die Aufzeichnung des Langzeit-EKGs nach einem Schema zu analysieren, um alle Auffälligkeiten zu erkennen. Wir schlagen ein schrittweises Vorgehen vor.

Abstract Background and Purpose Accurate and rapid assessment of coagulation status is necessary to guide thrombolysis or reversal of anticoagulation in stroke patients, but commercially available point-of-care (POC) assays are not suited for coagulation testing in patients treated with direct oral anticoagulants (DOACs). We aimed to evaluate the direct thrombin monitoring (DTM) test card by Helena Laboratories (Texas, United States) for anti-IIa-specific POC coagulation testing, hypothesizing that its POC-ecarin clotting time (POC-ECT) accurately reflects dabigatran plasma concentrations. Methods A prospective single-center diagnostic study (ClinicalTrials.gov-identifier: NCT02825394) was conducted enrolling patients receiving a first dose of dabigatran and patients already on dabigatran treatment. Blood samples were collected before drug intake and 0.5, 1, 2, 8, and 12 hours after intake. POC-ECT was performed using whole blood (WB), citrated blood (CB), and citrated plasma (CP). Dabigatran plasma concentrations were determined by mass spectrometry. Results In total, 240 blood samples from 40 patients contained 0 to 275 ng/mL of dabigatran. POC-ECT with WB/CB/CP ranged from 20 to 186/184/316 seconds. Pearson's correlation coefficient showed a strong correlation between dabigatran concentrations and POC-ECT with WB/CB/CP (R2  = 0.78/0.90/0.92). Dabigatran concentrations >30 and >50 ng/mL (thresholds for thrombolysis, surgery, and reversal therapy according to clinical guidelines) were detected by POC-ECT with WB/CB/CP (>36/35/45 and >43/45/59 seconds) with 95/97/97 and 96/98/97% sensitivity, and 81/87/94 and 74/60/91% specificity. Conclusion This first study evaluating DOAC-specific POC coagulation testing revealed an excellent correlation of POC-ECT with actual dabigatran concentrations. Detecting clinically relevant dabigatran levels with high sensitivity/specificity, the DTM assay represents a suitable diagnostic tool in acute stroke, hemorrhage, and urgent surgery.

The new guidelines of the ESC bring existing evidence from clinical trials on the diagnosis and management of atrial fibrillation (AF) into a clear perspective for clinical application. The general trend towards a more individual and personalized approach in the management of patients with atrial fibrillation becomes particular evident in two areas: the introduction of the concept of atrial fibrillation characterization with the 4S scheme (including stroke risk, symptoms, severity of AF burden and AF substrate), which is more precise compared to the traditional description of atrial fibrillation using the PPP classification (paroxysmal, persistent, permanent). Such a personalized approach is also evident from the recommendations for catheter ablation in which it is advised to consider and grade the risk of recurrence of atrial fibrillation after an ablation procedure before the intervention. Fully in line with the 2016 ESC guidelines is the promotion of the benefits of integrated care for patients with atrial fibrillation. With the introduction of the ABC treatment pathway the guidelines promote an intuitive and easy to follow approach for the establishment of the most important treatment steps: A for anticoagulation/avoid stroke, B for better symptoms, and C for comorbidities. Furthermore, the guidelines introduce for the first time recommendations for the systematic application of quality indicators and patient reported outcomes (PRO). In the field of anticoagulation for stroke prevention, the guidelines strengthen the role of non-vitamin K anticoagulants based on the individual stroke risk according to CHA(2)DS(2)-VASc and also recommend a more intense awareness of bleeding risks. Because new study data are lacking there is no change in the recommendation for interventional left atrial appendage occlusion (it remains IIb, can be considered). In the field of heart rate control treatment calcium antagonists and beta-blockers in combination with digitalis (if necessary) remain the first-line treatment. In rhythm control with antiarrhythmic drugs the role of sotalol was justifiably downgraded because of the well-known treatment side effects and risks. Atrial fibrillation catheter ablation was upgraded for patients with atrial fibrillation and structural heart disease and HFrEF (now IIa) but also for patients with so-called tachycardia-induced severe heart failure (now IB). Shortly after the publication of the 2020 ESC AF guidelines the results of the EAST trial were presented. This comment puts the results of EAST into the perspective of the 2020 ESC AF guidelines.