[Digital competence in rhythmology : Training and education]. / Digitale Kompetenzen in der Rhythmologie : Training und Ausbildung.

BACKGROUND: The digital transformation in medicine, particularly in technology-orientated areas such as rhythmology, is leading to a rapid change in diagnostic and therapeutic options. Digital skills are helpful and need to keep up with this pace of change. RESEARCH QUESTION: Which digital technologies and resources with rhythmological relevance play a role today and in the future? METHODS: Review of the various digital technologies for rhythm detection and monitoring, as well as current digital resources for training and education. RESULTS: Rhythm detection and monitoring can be optimized with smart devices and telemedicine, while digital platforms such as social media and virtual reality offer new perspectives in the training of rhythmology specialists. CONCLUSION: Acquiring digital skills will be the basis for future work in rhythmology.

Automated Signal Quality Assessment of Single-Lead ECG Recordings for Early Detection of Silent Atrial Fibrillation.

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.

Procedural performance between two cryoballoon systems for ablation of atrial fibrillation depends on pulmonary vein anatomy.

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.

MicroRNA-21 mediated cross-talk between cardiomyocytes and fibroblasts in patients with atrial fibrillation.

Background: Atrial 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. Methods: For 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. Results: 73.3% 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. Conclusion: We 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.

A Longer Tpeak-Tend Interval Is Associated with a Higher Risk of Death: A Meta-Analysis.

A noninvasive tool for cardiovascular risk stratification has not yet been established in the clinical routine analysis. Previous studies suggest a prolonged Tpeak-Tend interval (the interval from the peak to the end of the T-wave) to be predictive of death. This meta-analysis was designed to systematically evaluate the association of the Tpeak-Tend interval with mortality outcomes. Medline (via PubMed), Embase and the Cochrane Library were searched from 1 January 2008 to 21 July 2020 for articles reporting the ascertainment of the Tpeak-Tend interval and observation of all-cause-mortality. The search yielded 1920 citations, of which 133 full-texts were retrieved and 29 observational studies involving 23,114 patients met the final criteria. All-cause deaths had longer Tpeak-Tend intervals compared to survivors by a standardized mean difference of 0.41 (95% CI 0.23-0.58) and patients with a long Tpeak-Tend interval had a higher risk of all-cause death compared to patients with a short Tpeak-Tend interval by an overall odds ratio of 2.33 (95% CI 1.57-3.45). Heart rate correction, electrocardiographic (ECG) measurement methods and the selection of ECG leads were major sources of heterogeneity. Subgroup analyses revealed that heart rate correction did not affect the association of the Tpeak-Tend interval with mortality outcomes, whereas this finding was not evident in all measurement methods. The Tpeak-Tend interval was found to be significantly associated with all-cause mortality. Further studies are warranted to confirm the prognostic value of the Tpeak-Tend interval.

Extended ECG Improves Classification of Paroxysmal and Persistent Atrial Fibrillation Based on P- and f-Waves.

Background: The standard 12-lead ECG has been shown to be of value in characterizing atrial conduction properties. The added value of extended ECG recordings (longer recordings from more sites) has not been systematically explored yet. Objective: The aim of this study is to employ an extended ECG to identify characteristics of atrial electrical activity related to paroxysmal vs. persistent atrial fibrillation (AF). Methods: In 247 participants scheduled for AF ablation, an extended ECG was recorded (12 standard plus 3 additional leads, 5 min recording, no filtering). For patients presenting in sinus rhythm (SR), the signal-averaged P-wave and the spatiotemporal P-wave variability was analyzed. For patients presenting in AF, f-wave properties in the QRST (the amplitude complex of the ventricular electrical activity: Q-, R-, S-, and T-wave)-canceled ECG were determined. Results: Significant differences between paroxysmal (N = 152) and persistent patients with AF (N = 95) were found in several P-wave and f-wave parameters, including parameters that can only be calculated from an extended ECG. Furthermore, a moderate, but significant correlation was found between echocardiographic parameters and P-wave and f-wave parameters. There was a moderate correlation of left atrial (LA) diameter with P-wave energy duration (r = 0.317, p < 0.001) and f-wave amplitude in lead A3 (r = -0.389, p = 0.002). The AF-type classification performance significantly improved when parameters calculated from the extended ECG were taken into account [area under the curve (AUC) = 0.58, interquartile range (IQR) 0.50-0.64 for standard ECG parameters only vs. AUC = 0.76, IQR 0.70-0.80 for extended ECG parameters, p < 0.001]. Conclusion: The P- and f-wave analysis of extended ECG configurations identified specific ECG features allowing improved classification of paroxysmal vs. persistent AF. The extended ECG significantly improved AF-type classification in our analyzed data as compared to a standard 10-s 12-lead ECG. Whether this can result in a better clinical AF type classification warrants further prospective study.

Clinical and electrophysiological predictors of device-detected new-onset atrial fibrillation during 3 years after cardiac surgery.

AIMS: Postoperative atrial fibrillation (POAF) after cardiac surgery is an independent predictor of stroke and mortality late after discharge. We aimed to determine the burden and predictors of early (up to 5th postoperative day) and late (after 5th postoperative day) new-onset atrial fibrillation (AF) using implantable loop recorders (ILRs) in patients undergoing open chest cardiac surgery. METHODS AND RESULTS: Seventy-nine patients without a history of AF undergoing cardiac surgery underwent peri-operative high-resolution mapping of electrically induced AF and were followed 36 months after surgery using an ILR (Reveal XT™). Clinical and electrophysiological predictors of late POAF were assessed. POAF occurred in 46 patients (58%), with early POAF detected in 27 (34%) and late POAF in 37 patients (47%). Late POAF episodes were short-lasting (mostly between 2 min and 6 h) and showed a circadian rhythm pattern with a peak of episode initiation during daytime. In POAF patients, electrically induced AF showed more complex propagation patterns than in patients without POAF. Early POAF, right atrial (RA) volume, prolonged PR time, and advanced age were independent predictors of late POAF. CONCLUSIONS: Late POAF occurred in 47% of patients without a history of AF. Patients who develop early POAF, with higher age, larger RA, or prolonged PR time have a higher risk of developing late POAF and may benefit from intensified rhythm follow-up after cardiac surgery. CLINICALTRIALS.GOV NUMBER: NCT01530750.

Pulmonary vein isolation in a real-world population does not influence QTc interval.

AIMS: We aimed to examine whether routine pulmonary vein isolation (PVI) induces significant ventricular repolarization changes as suggested earlier. METHODS AND RESULTS: Five-minute electrocardiograms were recorded at hospital's admission (T-1d), 1 day after the PVI-procedure (T+1d) and at 3 months post-procedure (T+3m) from a registry of consecutive atrial fibrillation (AF) patients scheduled for routine PVI with different PVI modalities (radiofrequency, cryo-ablation, and hybrid). Only patients who were in sinus rhythm at all three recordings (n = 117) were included. QT-intervals and QT-dispersion were evaluated with custom-made software and QTc was calculated using Bazett's, Fridericia's, Framingham's, and Hodges' formulas. Both QT- and RR-intervals were significantly shorter at T+1d (399 ± 37 and 870 ± 141 ms) and T+3m (407 ± 36 and 950 ± 140 ms) compared with baseline (417 ± 36 and 1025 ± 164 ms). There was no statistically significant within-subject difference in QTc Fridericia (T-1d 416 ± 28 ms, T+1d 419 ± 33 ms, and T+3m 414 ± 25 ms) and QT-dispersion (T-1d 18 ± 12 ms, T+1d 21 ± 19 ms, and T+3m 17 ± 12 ms) between the recordings. A multiple linear regression model with age, sex, AF type, ablation technique, first/re-do ablation, and AF recurrence to predict the change in QTc at T+3m with respect to QTc at T-1d did not reach significance which indicates that the change in QTc does not differ between all subgroups (age, sex, AF type, ablation technique, first/re-do ablation, and AF recurrence). CONCLUSION: Based on our data a routine PVI does not result in a prolongation of QTc in a real-world population. These findings, therefore, suggest that there is no need to intensify post-PVI QT-interval monitoring.

Screen-detected atrial fibrillation predicts mortality in elderly subjects.

AIMS: Current guidelines recommend opportunistic screening for atrial fibrillation (AF) but the prognosis of individuals is unclear. The aim of this investigation is to determine prevalence and 1-year outcome of individuals with screen-detected AF. METHODS AND RESULTS: We performed a prospective, pharmacy-based single time point AF screening study in 7107 elderly citizens (≥65 years) using a hand-held, single-lead electrocardiogram (ECG) device. Prevalence of AF was assessed, and data on all-cause death and hospitalization for cardiovascular (CV) causes were collected over a median follow-up of 401 (372; 435) days. Mean age of participants was 74 ± 5.9 years, with 58% (N = 4130) of female sex. Automated heart rhythm analyses identified AF in 432 (6.1%) participants, with newly diagnosed AF in 3.6% of all subjects. During follow-up, 62 participants (0.9%) died and 390 (6.0%) were hospitalized for CV causes. Total mortality was 2.3% in participants with a screen-detected AF and 0.8% in subjects with a normal ECG [hazard ratio (HR) 2.94; 95% confidence interval (CI) 1.49-5.78; P = 0.002]; hospitalization for CV causes occurred in 10.6% and 5.5%, respectively (HR 2.08; 95% CI 1.52-2.84; P < 0.001). Compared with subjects without a history of AF at baseline and a normal ECG, participants with newly diagnosed or known AF had a significantly higher mortality risk with HRs of 2.64 (95% CI 1.05-6.66; P = 0.04) and 2.68 (95% CI 1.44-4.97; P = 0.002), respectively. After multivariable adjustment, screen-detected AF remained a significant predictor of death or hospitalization for CV causes. CONCLUSION: Pharmacy-based, automated AF screening in elderly citizens identified subjects with unknown AF and an excess mortality risk over the next year.

Experience in screening for atrial fibrillation and monitoring arrhythmia using a single-lead ECG stick.

Atrial fibrillation (AF) is the most common arrhythmia and is highly associated with increased morbidity and mortality. Since many AF episodes remain subclinical, screening for AF is considered a desirable approach for timely diagnosis, prevention of sequelae and effective treatment. Recently, devices for AF detection-stand-alone or integrated in mobile health technology-have become available and show promising preliminary results in the detection and monitoring of arrhythmia. This review describes the technical aspects of a single-lead ECG stick and summarizes the current literature, experience in large-scale screening for AF in pharmacies and potential fields of application.

Predictors of recurrence of atrial fibrillation within the first 3 months after ablation.

AIMS: Freedom from atrial fibrillation (AF) at 1 year can be achieved in 50-70% of patients undergoing catheter ablation. Recurrent AF early after ablation most commonly terminates spontaneously without further interventional treatment but is associated with later recurrent AF. The aim of this investigation is to identify clinical and procedural factors associated with recurrence of AF early after ablation. METHODS AND RESULTS: We retrospectively analysed data for recurrence of AF within the first 3 months after catheter ablation from the randomized controlled AXAFA-AFNET 5 trial, which demonstrated that continuous anticoagulation with apixaban is as safe and as effective compared to vitamin K antagonists in 678 patients undergoing first AF ablation. The primary outcome of first recurrent AF within 90 days was observed in 163 (28%) patients, in which 78 (48%) patients experienced an event within the first 14 days post-ablation. After multivariable adjustment, a history of stroke/transient ischaemic attack [hazard ratio (HR) 1.54, 95% confidence interval (CI) 0.93-2.6; P = 0.11], coronary artery disease (HR 1.85, 95% CI 1.20-2.86; P = 0.005), cardioversion during ablation (HR 1.78, 95% CI 1.26-2.49; P = 0.001), and an age:sex interaction for older women (HR 1.01, 95% CI 1.00-1.01; P = 0.04) were associated with recurrent AF. The P-wave duration at follow-up was significantly longer for patients with AF recurrence (129 ± 31 ms vs. 122 ± 22 ms in patients without AF, P = 0.03). CONCLUSION: Half of all early AF recurrences within the first 3 months post-ablation occurred within the first 14 days post-ablation. Vascular disease and cardioversion during the procedure are strong predictors of recurrent AF. P-wave duration at follow-up was longer in patients with recurrent AF. TRIAL REGISTRATION: Clinicaltrials.gov identifier NCT02227550.

Segmental Bioelectrical Impedance Spectroscopy to Monitor Fluid Status in Heart Failure.

Bioelectrical impedance spectroscopy (BIS) measures body composition, including fluid status. Acute decompensated heart failure (ADHF) is associated with fluid overload in different body compartments. This investigation aimed to evaluate the feasibility of measuring and monitoring fluid accumulation in patients with ADHF using BIS. The extracellular impedance as a surrogate marker for fluid accumulation was measured in 67 participants (25 healthy reference volunteers and 42 patients admitted with ADHF) using BIS in the "transthoracic", "foot-to-foot", "whole-body" and "hand-to-hand" segments. At baseline, BIS showed significantly lower extracellular resistance values for the "whole-body" (P < 0.001), "foot-to-foot" (P = 0.03), "hand-to-hand" (P < 0.001) and "transthoracic" (P = 0.014) segments in patients with ADHF than the reference cohort, revealing a specific pattern for peripheral, central and general fluid accumulation. The "foot-to-foot" (AUC = 0.8, P < 0.001) and "hand-to-hand" (AUC = 0.74, P = 0.04) segments indicated compartments of fluid accumulation with good prediction. During cardiac recompensation, BIS values changed significantly and were in line with routine parameters for monitoring ADHF. Mean bodyweight change per day correlated moderately to good with BIS values in the "whole-body" (r = -0.4), "foot-to-foot" (r = -0.8) and "transthoracic" (r = -0.4) segments. Based on our analysis, we conclude that measuring and monitoring fluid accumulation in ADHF using segmental BIS is feasible and correlates with clinical parameters during recompensation.

Incidence and predictors of pacemaker induced cardiomyopathy: A single-center experience.

BACKGROUND: Pacemaker induced Cardiomyopathy (PICM) is an easily overlooked cause of heart failure with reduced ejection fraction. Data regarding this complication are sparse. Therefore, the aim of this study was to identify the incidence and predictors of PICM. METHODS: Between 2011 and 2017, 857 consecutive patients undergoing pacemaker (PM) implantation, were reviewed, and according to our inclusion criteria 173 individuals were enrolled in this retrospective single center study. All patients included had normal left ventricular ejection fraction (LVEF) before implantation, underwent single-chamber ventricular or dual-chamber PM implantation, had RV pacing burden ≥20%, and repeated echocardiogram was available ≥1 year after implantation. PICM was defined as deterioration LVEF ≥10%, resulting in LVEF <50%, which cannot be explained by other causes. RESULTS: During a mean follow-up of 39.9 ±â€¯21.0 months, PICM occurred in 26 patients (16%). RV pacing percentage did not differ significantly between the both groups (76.5 vs 76.2%, p = 0.65). The PICM group patients were likely to be men (p = 0.002) and had a lower rate of arterial hypertension (p = 0.01). Multivariate analysis revealed male sex (HR 6.45, 0.95 CI 1.90-21.86, p = 0.003) and wider paced QRS complex (HR 1.04, 95% CI 1.02-1.07, p < 0.001) as predictors of PICM. CONCLUSIONS: In patients with frequent RV pacing, the prevalence of PICM is not uncommon. Male sex and wider paced QRS complex are independent predictors of PICM and these patients may require closer follow-up.

Amino Acid-Substituted Dextran-Based Non-Viral Vectors for Gene Delivery.

To form bio-inspired non-viral vectors for DNA delivery, the polysaccharide dextran is allowed to react with Boc-amino protected amino acids glycine, ß-alanine, and L-lysine activated with 1,1'-carbonyldiimidazole and subsequent dextran ester deprotection. A library of such dextran esters is made available to investigate the relationship between polymer structure, complex formation, stability, toxicity, and transfection. Only dextran esters of ß-alanine and L-lysine are able to efficiently interact with DNA as shown by dye exclusion assays, to form nanosized complexes (70-110 nm) with positive zeta potential. With increasing substitution degree and complex charge ratios, the L-lysine esters accomplish more effective binding and protection of DNA against enzymatic degradation than ß-alanine esters. However, luciferase reporter gene assays reveal higher transfection for ß-alanine than for L-lysine esters due to a more effective DNA release and better suited buffing area of the amino groups triggering the endosomal release. Conclusively, ß-alanine-substituted dextran derivatives may serve as promising non-viral vectors.

Opportunities and challenges of large-scale screening for atrial fibrillation.

Atrial fibrillation (AF) is a common arrhythmia and is highly associated with stroke and cardiovascular morbidity. As many AF episodes remain subclinical (SCAF), large-scale AF screening is considered a desirable approach for the treatment and prevention of cardioembolic stroke. Newly available single-lead ECG devices have provided promising results in the diagnosis of SCAF and treatment by nonvitamin K antagonist drugs appears to be safe and effective. Nevertheless, a further gain in knowledge is needed to clarify the different types of AF. This may help to define how or if a patient should be treated in the context of outcome and cost effectiveness. This review summarizes the results of recent research in this field and focuses on single-lead, discontinuous single time-point, community-based comprehensive-screening-based AF management. We want to conclude that progress in ECG diagnosis and anticoagulation therapy has prepared the ground to establish large-scale AF screening. The remaining question, however, is which patients should be screened and what therapy should be initiated in case of AF.

Concealed abnormal atrial phenotype in patients with Brugada syndrome and no history of atrial fibrillation.

OBJECTIVES: The electrocardiogram (ECG) of patients with BrS in sinus rhythm might reflect intrinsic atrial electrical abnormalities independent from any previous atrial fibrillation (AF). Aim of this study is to investigate the presence of P-wave abnormalities in patients with BrS and no history of AF, and to compare them with those displayed by patients with documented paroxysmal AF and by healthy subjects. METHODS: Continuous 5-min 16-lead ECG recordings in sinus rhythm were obtained from 72 participants: 32 patients with a type 1 Brugada ECG, 20 patients with a history of paroxysmal AF and 20 age-matched healthy subjects. Different ECG-based features were computed on the P-wave first principal component representing the predominant morphology across leads and containing the maximal information on atrial depolarization: duration, full width half maximum (FWHM), area under the curve and number of peaks in the wave. RESULTS: Patients with BrS and no history of AF (mean age: 53±12years; males: 28 pts., spontaneous type 1 ECG: 20 pts., SCN5A mutation: 10 pts) presented with longer P-wave duration, higher FWHM and wider area under the curve in comparison with the other two groups. Although P-wave features were abnormal in BrS patients, no significant difference was found between patients with spontaneous type 1 ECG and ajmaline-induced type 1 ECG, symptomatic and asymptomatic ones, and between patients with a pathogenic SCNA5 mutation and patients without a known gene mutation. CONCLUSIONS: Patients with BrS without previous occurrence of AF present with a concealed abnormal atrial phenotype. In these patients atrial electrical abnormalities can be detected even in the absence of an overt ECG ventricular phenotype, symptoms and a SCN5A mutation.