Same-day discharge after atrial fibrillation ablation under a nurse-coordinated standardized protocol.

AIMS: Same-day discharge (SDD) after atrial fibrillation (AF) ablation is an effective means to spare healthcare resources. However, safety remains a concern, and besides structural adaptations, SDD requires more efficient logistics and coordination. Therefore, in this study, we implement a streamlined, nurse-coordinated SDD programme following a standardized protocol. METHODS AND RESULTS: As a dedicated SDD coordinator, a nurse specialized in ambulatory cardiac interventions was in charge of the full SDD protocol, including eligibility, patient flow, in-hospital logistics, patient education, and discharge as well as early post-discharge follow-up by smartphone-based virtual visits. Patients planned for AF ablation were considered eligible if they had a left ventricular ejection fraction (LVEF) ≥35%, with basic support at home and accessibility of the hospital within 60 min also forming a part of the eligibility criteria. A total of 420 consecutive patients were screened by the SDD coordinator, of whom 331 were eligible for SDD. The reasons for exclusion were living remotely (29, 6.9%), lack of support at home (19, 4.5%), or LVEF <35% (17, 4.0%). Of the eligible patients, 300 (91%) were successfully discharged the same day. There were no major post-SDD complications. Rates of unplanned medical attention (19, 6.3%) and 30-day readmission (5, 1.6%) were extremely low and driven by femoral access-site complications. These were significantly reduced upon the introduction of compulsory ultrasound-guided punctures after the initial 150 SDD patients (P = 0.0145). Standardized SDD coordination resulted in efficient workflows and reduced the total workload of the medical staff. CONCLUSION: Same-day discharge after AF ablation following a nurse-coordinated standardized protocol is safe and efficient. The concept of ambulatory cardiac intervention nurses functioning as dedicated coordinators may be key in the future transition of hospitals to SDD. Ultrasound-guided femoral puncture virtually eliminated relevant femoral access-site complications in our cohort and should therefore be a prerequisite for SDD.

Regional conduction velocities determined by non-invasive mapping are associated with arrhythmia-free survival after atrial fibrillation ablation.

BACKGROUND: Atrial arrhythmogenic substrate is a key determinant of atrial fibrillation (AF) recurrence after pulmonary vein isolation (PVI), and reduced conduction-velocities have been linked to adverse outcome. However, a non-invasive method to assess such electrophysiological substrate is not available to date. OBJECTIVE: This study aimed to non-invasively assess regional conduction-velocities and their association with arrhythmia-free survival following PVI. METHODS: 52 consecutive patients scheduled for AF ablation (PVI-only) and 19 healthy controls were prospectively included and received electrocardiographic imaging (ECGi) to non-invasively determine regional atrial conduction-velocities in sinus rhythm. A novel ECGi technology obviating the need of additional CT- or CMR-imaging was applied and validated using invasive mapping. RESULTS: Mean ECGi-determined atrial conduction-velocities were significantly lower in AF-patients than in healthy controls (1.45±0.15 versus 1.64±0.15m/s; p<0.0001). Differences were particularly pronounced in a regional analysis considering only the segment with the lowest average conduction-velocity in each patient (0.8±0.22 versus 1.08±0.26m/s; p<0.0001). This average conduction velocity of the "slowest" segment was independently associated with arrhythmia recurrence and better discriminated between PVI-responders and non-responders than previously proposed predictors including left atrial size or late-gadolinium-enhancement (MRI). Patients without slow-conduction areas (mean conduction-velocity <0.78m/s) showed significantly higher 12-months arrhythmia-free survival than those with one or more slow-conduction areas (88.9% versus 48.0%, p=0.002). CONCLUSIONS: This is the first study to investigate regional atrial conduction velocities non-invasively. The absence of ECGi-determined slow-conduction areas well discriminates PVI-responders from non-responders. Such non-invasive assessment of electrical arrhythmogenic substrate may guide treatment strategies and be a step towards personalised AF therapy.

Management of Ventricular Arrhythmias in Heart Failure.

PURPOSE OF REVIEW: Despite substantial progress in medical and device-based heart failure (HF) therapy, ventricular arrhythmias (VA) and sudden cardiac death (SCD) remain a major challenge. Here we review contemporary management of VA in the context of HF with one particular focus on recent advances in imaging and catheter ablation. RECENT FINDINGS: Besides limited efficacy of antiarrhythmic drugs (AADs), their potentially life-threatening side effects are increasingly acknowledged. On the other hand, with tremendous advances in catheter technology, electroanatomical mapping, imaging, and understanding of arrhythmia mechanisms, catheter ablation has evolved into a safe, efficacious therapy. In fact, recent randomized trials support early catheter ablation, demonstrating superiority over AAD. Importantly, CMR imaging with gadolinium contrast has emerged as a central tool for the management of VA complicating HF: CMR is not only essential for an accurate diagnosis of the underlying entity and subsequent treatment decisions, but also improves risk stratification for SCD prevention and patient selection for ICD therapy. Finally, 3-dimensional characterization of arrhythmogenic substrate by CMR and imaging-guided ablation approaches substantially enhance procedural safety and efficacy. VA management in HF patients is highly complex and should be addressed in a multidisciplinary approach, preferably at specialized centers. While recent evidence supports early catheter ablation of VA, an impact on mortality remains to be demonstrated. Moreover, risk stratification for ICD therapy may have to be reconsidered, taking into account imaging, genetic testing, and other parameters beyond left ventricular function.

Cuantificación de la fibrosis auricular derecha mediante resonancia magnética cardiaca: verificación del método para la estandarización de umbrales' / Quantification of right atrial fibrosis by cardiac magnetic resonance: verification of the method to standardize thresholds

Introducción y objetivos La resonancia magnética cardiaca con realce tardío de gadolinio (RMC-RTG) permite la detección no invasiva de la fibrosis auricular izquierda en pacientes con fibrilación auricular (FA). Sin embargo, se desconoce si se puede utilizar la misma metodología en la aurícula derecha (AD). Nuestro objetivo fue definir un umbral estandarizado para caracterizar la fibrosis auricular derecha mediante RMC-RTG. Métodos Se realizaron RMC-RTG de 3 T en 53 personas; se segmentó la AD y se calculó la razón de intensidad de imagen (RII) para la pared de la AD utilizando 1.557.767 píxeles de RII (40.994±10.693 por paciente). El límite superior de la normalidad de la RII (RII promedio+2 desviaciones estándar) se estimó en voluntarios sanos (n = 9); para establecer el umbral de cicatriz densa, se utilizó a los pacientes que se habían sometido previamente a una ablación del flutter auricular típico (n = 9). Se incluyó a pacientes con FA paroxística y persistente (n=10 cada grupo) para la validación. Los valores de RII se correlacionaron con un mapa de voltaje bipolar de alta densidad en 15 pacientes sometidos a ablación de FA. Resultados El límite superior de la normalidad (umbral de fibrosis total) en voluntarios sanos se fijó en RII = 1,21. En el grupo postablación, el 60% del píxel de la RII máximo (umbral de fibrosis densa) se calculó como RII = 1,29. El voltaje bipolar endocárdico mostró una correlación con la RII débil pero significativa. La precisión general entre el mapa electroanatómico y la RMC-RTG para caracterizar la fibrosis fue del 56%. Conclusiones Se determinó una RII > 1,21 como umbral para la detección de fibrosis de la aurícula derecha, mientras que una RII > 1,29 diferencia la fibrosis intersticial de la cicatriz densa. A pesar de las diferencias entre las aurículas izquierda y derecha, se pudo evaluar la fibrosis con RMC-RTG con umbrales similares en ambas cámaras (AU)

Introduction and objectives Late gadolinium-enhanced cardiac magnetic resonance (LGE-CMR) allows noninvasive detection of left atrial fibrosis in patients with atrial fibrillation (AF). However, whether the same methodology can be used in the right atrium (RA) remains unknown. Our aim was to define a standardized threshold to characterize RA fibrosis in LGE-CMR. Methods A 3 Tesla LGE-CMR was performed in 53 individuals; the RA was segmented, and the image intensity ratio (IIR) calculated for the RA wall using 1 557 767 IIR pixels (40 994±10 693 per patient). The upper limit of normality of the IIR (mean IIR+2 standard deviations) was estimated in healthy volunteers (n=9), and patients who had undergone previous typical atrial flutter ablation (n=9) were used to establish the dense scar threshold. Paroxysmal and persistent AF patients (n=10 each) were used for validation. IIR values were correlated with a high-density bipolar voltage map in 15 patients undergoing AF ablation. Results The upper normality limit (total fibrosis threshold) in healthy volunteers was set at an IIR = 1.21. In the postablation group, 60% of the maximum IIR pixel (dense fibrosis threshold) was calculated as IIR = 1.29. Endocardial bipolar voltage showed a weak but significant correlation with IIR. The overall accuracy between the electroanatomical map and LGE-CMR to characterize fibrosis was 56%. Conclusions An IIR > 1.21 was determined to be the threshold for the detection of right atrial fibrosis, while an IIR > 1.29 differentiates interstitial fibrosis from dense scar. Despite differences between the left and right atria, fibrosis could be assessed with LGE-CMR using similar thresholds in both chambers (AU)

Gq-Mediated Arrhythmogenic Signaling Promotes Atrial Fibrillation.

BACKGROUND: Atrial fibrillation (AF) is promoted by various stimuli like angiotensin II, endothelin-1, epinephrine/norepinephrine, vagal activation, or mechanical stress, all of which activate receptors coupled to G-proteins of the Gαq/Gα11-family (Gq). Besides pro-fibrotic and pro-inflammatory effects, Gq-mediated signaling induces inositol trisphosphate receptor (IP3R)-mediated intracellular Ca2+ mobilization related to delayed after-depolarisations and AF. However, direct evidence of arrhythmogenic Gq-mediated signaling is absent. METHODS AND RESULTS: To define the role of Gq in AF, transgenic mice with tamoxifen-inducible, cardiomyocyte-specific Gαq/Gα11-deficiency (Gq-KO) were created and exposed to intracardiac electrophysiological studies. Baseline electrophysiological properties, including heart rate, sinus node recovery time, and atrial as well as AV nodal effective refractory periods, were comparable in Gq-KO and control mice. However, inducibility and mean duration of AF episodes were significantly reduced in Gq-KO mice-both before and after vagal stimulation. To explore underlying mechanisms, left atrial cardiomyocytes were isolated from Gq-KO and control mice and electrically stimulated to study Ca2+-mobilization during excitation-contraction coupling using confocal microscopy. Spontaneous arrhythmogenic Ca2+ waves and sarcoplasmic reticulum content-corrected Ca2+ sparks were less frequent in Gq-KO mice. Interestingly, nuclear but not cytosolic Ca2+ transient amplitudes were significantly decreased in Gq-KO mice. CONCLUSION: Gq-signaling promotes arrhythmogenic atrial Ca2+-release and AF in mice. Targeting this pathway, ideally using Gq-selective, biased receptor ligands, may be a promising approach for the treatment and prevention of AF. Importantly, the atrial-specific expression of the Gq-effector IP3R confers atrial selectivity mitigating the risk of life-threatening ventricular pro-arrhythmic effects.

Predictive value of late gadolinium enhancement cardiovascular magnetic resonance in patients with persistent atrial fibrillation: dual-centre validation of a standardized method.

Aims: With recurrence rates up to 50% after pulmonary vein isolation (PVI) in persistent atrial fibrillation (AF), predictive tools to improve patient selection are needed. Patient selection based on left atrial late gadolinium enhancement (LGE) cardiovascular magnetic resonance (CMR) has been proposed previously (UTAH-classification). However, this approach has not been widely established, in part owed to the lack of standardization of the LGE quantification method. We have recently established a standardized LGE-CMR method enabling reproducible LGE-quantification. Here, the ability of this method to predict outcome after PVI was evaluated. Methods and results: This dual-centre study (n = 219) consists of a prospective derivation cohort (n = 37, all persistent AF) and an external validation cohort (n = 182; 66 persistent, 116 paroxysmal AF). All patients received an LGE-CMR prior to first-time PVI-only ablation. LGE was quantified based on the signal-intensity-ratio relative to the blood pool, applying a uniform LGE-defining threshold of >1.2.  In patients with persistent AF in the derivation cohort, left atrial LGE-extent above a cut-off value of 12% was found to best predict relevant low-voltage substrate (≥2 cm two with <0.5 mV during sinus rhythm) and arrhythmia-free survival 12 months post-PVI. When applied to the external validation cohort, this cut-off value was also predictive of arrhythmia-free survival for both, the total cohort and the subgroup with persistent AF (LGE < 12%: 80% and 76%; LGE > 12%: 55% and 44%; P = 0.007 and P = 0.029, respectively). Conclusion: This dual-centre study established and validated a standardized, reproducible LGE-CMR method discriminating PVI responders from non-responders, which may improve choice of therapeutic approach or ablation strategy for patients with persistent AF.

Non-invasive assessment of pulmonary vein isolation durability using late gadolinium enhancement magnetic resonance imaging.

AIMS: Electrical reconnection of pulmonary veins (PVs) is considered an important determinant of recurrent atrial fibrillation (AF) after pulmonary vein isolation (PVI). To date, AF recurrences almost automatically trigger invasive repeat procedures, required to assess PVI durability. With recent technical advances, it is becoming increasingly common to find all PVs isolated in those repeat procedures. Thus, as ablation of extra-PV targets has failed to show benefit in randomized trials, more and more often these highly invasive procedures are performed only to rule out PV reconnection. Here we aim to define the ability of late gadolinium enhancement (LGE)-magnetic resonance imaging (MRI) to rule out PV reconnection non-invasively. METHODS AND RESULTS: This study is based on a prospective registry in which all patients receive an LGE-MRI after AF ablation. Included were all patients that-after an initial PVI and post-ablation LGE-MRI-underwent an invasive repeat procedure, which served as a reference to determine the predictive value of non-invasive lesion assessment by LGE-MRI.: 152 patients and 304 PV pairs were analysed. LGE-MRI predicted electrical PV reconnection with high sensitivity (98.9%) but rather low specificity (55.6%). Of note, LGE lesions without discontinuation ruled out reconnection of the respective PV pair with a negative predictive value of 96.9%, and patients with complete LGE lesion sets encircling all PVs were highly unlikely to show any PV reconnection (negative predictive value: 94.4%). CONCLUSION: LGE-MRI has the potential to guide selection of appropriate candidates and planning of the ablation strategy for repeat procedures and may help to identify patients that will not benefit from a redo-procedure if no ablation of extra-PV targets is intended.

Quantification of right atrial fibrosis by cardiac magnetic resonance: verification of the method to standardize thresholds.

INTRODUCTION AND OBJECTIVES: Late gadolinium-enhanced cardiac magnetic resonance (LGE-CMR) allows noninvasive detection of left atrial fibrosis in patients with atrial fibrillation (AF). However, whether the same methodology can be used in the right atrium (RA) remains unknown. Our aim was to define a standardized threshold to characterize RA fibrosis in LGE-CMR. METHODS: A 3 Tesla LGE-CMR was performed in 53 individuals; the RA was segmented, and the image intensity ratio (IIR) calculated for the RA wall using 1 557 767 IIR pixels (40 994±10 693 per patient). The upper limit of normality of the IIR (mean IIR+2 standard deviations) was estimated in healthy volunteers (n=9), and patients who had undergone previous typical atrial flutter ablation (n=9) were used to establish the dense scar threshold. Paroxysmal and persistent AF patients (n=10 each) were used for validation. IIR values were correlated with a high-density bipolar voltage map in 15 patients undergoing AF ablation. RESULTS: The upper normality limit (total fibrosis threshold) in healthy volunteers was set at an IIR = 1.21. In the postablation group, 60% of the maximum IIR pixel (dense fibrosis threshold) was calculated as IIR = 1.29. Endocardial bipolar voltage showed a weak but significant correlation with IIR. The overall accuracy between the electroanatomical map and LGE-CMR to characterize fibrosis was 56%. CONCLUSIONS: An IIR > 1.21 was determined to be the threshold for the detection of right atrial fibrosis, while an IIR > 1.29 differentiates interstitial fibrosis from dense scar. Despite differences between the left and right atria, fibrosis could be assessed with LGE-CMR using similar thresholds in both chambers.

Progressive and Simultaneous Right and Left Atrial Remodeling Uncovered by a Comprehensive Magnetic Resonance Assessment in Atrial Fibrillation.

Background Left atrial structural remodeling contributes to the arrhythmogenic substrate of atrial fibrillation (AF), but the role of the right atrium (RA) remains unknown. Our aims were to comprehensively characterize right atrial structural remodeling in AF and identify right atrial parameters predicting recurrences after ablation. Methods and Results A 3.0 T late gadolinium enhanced-cardiac magnetic resonance was obtained in 109 individuals (9 healthy volunteers, 100 patients with AF undergoing ablation). Right and left atrial volume, surface, and sphericity were quantified. Right atrial global and regional fibrosis burden was assessed with validated thresholds. Patients with AF were systematically followed after ablation for recurrences. Progressive right atrial dilation and an increase in sphericity were observed from healthy volunteers to patients with paroxysmal and persistent AF; fibrosis was similar among the groups. The correlation between parameters recapitulating right atrial remodeling was mild. Subsequently, remodeling in both atria was compared. The RA was larger than the left atrium (LA) in all groups. Fibrosis burden was higher in the LA than in the RA of patients with AF, whereas sphericity was higher in the LA of patients with persistent AF only. Fibrosis, volume, and surface of the RA and LA, but not sphericity, were strongly correlated. Tricuspid regurgitation predicted right atrial volume and shape, whereas diabetes was associated with right atrial fibrosis burden; sex and persistent AF also predicted right atrial volume. Fibrosis in the RA was mostly located in the inferior vena cava-RA junction. Only right atrial sphericity is significantly associated with AF recurrences after ablation (hazard ratio, 1.12 [95% CI, 1.01-1.25]). Conclusions AF progression associates with right atrial remodeling in parallel with the LA. Right atrial sphericity yields prognostic significance after ablation.

Ablation Lesion Assessment with MRI.

Late gadolinium enhancement (LGE) MRI is capable of detecting not only native cardiac fibrosis, but also ablation-induced scarring. Thus, it offers the unique opportunity to assess ablation lesions non-invasively. In the atrium, LGE-MRI has been shown to accurately detect and localise gaps in ablation lines. With a negative predictive value close to 100% it can reliably rule out pulmonary vein reconnection non-invasively and thus may avoid unnecessary invasive repeat procedures where a pulmonary vein isolation only approach is pursued. Even LGE-MRI-guided repeat pulmonary vein isolation has been demonstrated to be feasible as a standalone approach. LGE-MRI-based lesion assessment may also be of value to evaluate the efficacy of ventricular ablation. In this respect, the elimination of LGE-MRI-detected arrhythmogenic substrate may serve as a potential endpoint, but validation in clinical studies is lacking. Despite holding great promise, the widespread use of LGE-MRI is still limited by the absence of standardised protocols for image acquisition and post-processing. In particular, reproducibility across different centres is impeded by inconsistent thresholds and internal references to define fibrosis. Thus, uniform methodological and analytical standards are warranted to foster a broader implementation in clinical practice.

Late gadolinium enhancement-MRI determines definite lesion formation most accurately at 3 months post ablation compared to later time points.

AIMS: Neither the long-term development of ablation lesions nor the capability of late gadolinium enhancement (LGE)-MRI to detect ablation-induced fibrosis at late stages of scar formation have been defined. We sought to assess the development of atrial ablation lesions over time using LGE-MRI and invasive electroanatomical mapping (EAM). METHODS AND RESULTS: Ablation lesions and total atrial fibrosis were assessed in serial LGE-MRI scans 3 months and >12 months post pulmonary vein (PV) isolation. High-density EAM performed in subsequent repeat ablation procedures served as a reference. Serial LGE-MRI of 22 patients were analyzed retrospectively. The PV encircling ablation lines displayed an average LGE, indicative of ablation-induced fibrosis, of 91.7% ± 7.0% of the circumference at 3 months, but only 62.8% ± 25.0% at a median of 28 months post ablation (p < 0.0001). EAM performed in 18 patients undergoing a subsequent repeat procedure revealed that the consistent decrease in LGE over time was owed to a reduced detectability of ablation-induced fibrosis by LGE-MRI at time-points > 12 months post ablation. Accordingly, the agreement with EAM regarding detection of ablation-induced fibrosis and functional gaps was good for the LGE-MRI at 3 months (κ .74; p < .0001), but only weak for the LGE-MRI at 28 months post-ablation (κ .29; p < .0001). CONCLUSION: While non-invasive lesion assessment with LGE-MRI 3 months post ablation provides accurate guidance for future redo-procedures, detectability of atrial ablation lesions appears to decrease over time. Thus, it should be considered to perform LGE-MRI 3 months post-ablation rather than at later time-points > 12 months post ablation, like for example, prior to a planned redo-ablation procedure.

Novel concepts in atrial fibrillation ablation-breaking the trade-off between efficacy and safety.

Despite substantial technological and procedural advances that have improved the efficacy and safety of AF ablation in recent years, the long-term durability of ablation lesions is still not satisfactory. There also remains concern regarding rare but potentially life-threatening procedure-related complications like cardiac tamponade and atrioesophageal fistulae. Current ablation strategies are aiming to optimize the trade-off between efficacy and safety, where more extensive ablation appears to inevitably increase the risk of collateral injury. However, new forms of energy application may have the potential to resolve this quandary. The emerging concept of high power-short duration radiofrequency ablation features a more favorable lesion geometry that appears ideally suited to create contiguous lesions in the thin-walled atrium. Moreover, novel non-thermal ablation methods based on electroporation appear to provide a unique selectivity for cardiomyocytes and to spare surrounding tissues composed of other cell types. Both, high power-short duration and electroporation ablation might have the potential to break the trade-off between effective lesions and collateral damage and to substantially improve risk-benefit ratios in AF ablation. In addition, both approaches lead to considerable reductions in ablation times. However, their putative benefits regarding efficacy, efficiency, and safety remain to be proven in randomized controlled trials.

Accuracy of left atrial fibrosis detection with cardiac magnetic resonance: correlation of late gadolinium enhancement with endocardial voltage and conduction velocity.

AIMS: Myocardial fibrosis is a hallmark of atrial fibrillation (AF) and its characterization could be used to guide ablation procedures. Late gadolinium enhanced-magnetic resonance imaging (LGE-MRI) detects areas of atrial fibrosis. However, its accuracy remains controversial. We aimed to analyse the accuracy of LGE-MRI to identify left atrial (LA) arrhythmogenic substrate by analysing voltage and conduction velocity at the areas of LGE. METHODS AND RESULTS: Late gadolinium enhanced-magnetic resonance imaging was performed before ablation in 16 patients. Atrial wall intensity was normalized to blood pool and classified as healthy, interstitial fibrosis, and dense scar tissue depending of the resulting image intensity ratio. Bipolar voltage and local conduction velocity were measured in LA with high-density electroanatomic maps recorded in sinus rhythm and subsequently projected into the LGE-MRI. A semi-automatic, point-by-point correlation was made between LGE-MRI and electroanatomical mapping. Mean bipolar voltage and local velocity progressively decreased from healthy to interstitial fibrosis to scar. There was a significant negative correlation between LGE with voltage (r = -0.39, P < 0.001) and conduction velocity (r = -0.25, P < 0.001). In patients showing dilated atria (LA diameter ≥45 mm) the conduction velocity predictive capacity of LGE-MRI was weaker (r = -0.40 ± 0.09 vs. -0.20 ± 0.13, P = 0.02). CONCLUSIONS: Areas with higher LGE show lower voltage and slower conduction in sinus rhythm. The enhancement intensity correlates with bipolar voltage and conduction velocity in a point-by-point analysis. The performance of LGE-MRI in assessing local velocity might be reduced in patients with dilated atria (LA diameter ≥45).