The vascular endothelium is constantly exposed to mechanical forces, including fluid shear stress exerted by the flowing blood. Endothelial cells can sense different flow patterns and convert the mechanical signal of laminar flow into atheroprotective signals, including eNOS activation, whereas disturbed flow in atheroprone areas induces inflammatory signaling, including NF-κB activation. How endothelial cells distinguish different flow patterns is poorly understood. Here we show that both laminar and disturbed flow activate the same initial pathway involving the mechanosensitive cation channel Piezo1, the purinergic P2Y₂ receptor, and G_q/G₁₁-mediated signaling. However, only disturbed flow leads to Piezo1- and G_q/G₁₁-mediated integrin activation resulting in focal adhesion kinase-dependent NF-κB activation. Mice with induced endothelium-specific deficiency of Piezo1 or Gα_q/Gα₁₁ show reduced integrin activation, inflammatory signaling, and progression of atherosclerosis in atheroprone areas. Our data identify critical steps in endothelial mechanotransduction, which distinguish flow pattern-dependent activation of atheroprotective and atherogenic endothelial signaling and suggest novel therapeutic strategies to treat inflammatory vascular disorders such as atherosclerosis.

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.

Aims: While the CLOSE protocol proposes a maximally tolerable interlesion distance (ILD) of 6 mm for ablation index ablation index-guided atrial fibrillation (AF) ablation, a target ILD has never been defined. This randomized study sought to establish a target ILD for ablation index-guided AF ablation. Methods and results: Consecutive patients scheduled for first-time pulmonary vein (PV) isolation (PVI) were randomly assigned to ablation protocols with a target ILD of 5.0–6.0 mm or 3.0–4.0 mm, with the primary endpoint of first-pass PVI. In compliance with the CLOSE protocol, the maximum tolerated ILD was 6.0 mm in both study protocols. A target ablation index of ≥550 (anterior) or ≥400 (posterior) was defined for the ‘5–6 mm’ protocol and ≥500 (anterior) or ≥350 (posterior) for the ‘3–4 mm’ protocol. The study was terminated early for superiority of the ‘3–4 mm’ protocol. Forty-two consecutive patients were randomized and 84 ipsilateral PV pairs encircled according to the study protocol. First-pass PVI was accomplished in 35.0% of the ‘5–6 mm’ group and 90.9% of the ‘3–4 mm’ group (P < 0.0001). Median ILD was 5.2 mm in the ‘5–6 mm’ group and 3.6 mm in the ‘3–4 mm’ group (P < 0.0001). In line with the distinct ablation index targets, median ablation index was lower in the ‘3–4 mm’ group (416 vs. 452, P < 0.0001). While mean procedure time was shorter in the ‘3–4 mm’ group (149 ± 27 vs. 167 ± 33min, P = 0.004), fluoroscopy times did not differ significantly (4.7 ± 2.2 vs. 5.1 ± 1.8 min, P = 0.565). Conclusion: In ablation index-guided AF ablation, an ILD of 3.0–4.0 mm should be targeted rather than 5.0–6.0 mm. Moreover, the lower target ILD may allow for less extensive ablation at each given point.

This clinical consensus document proposes standardized atrial segments for 3D imaging, electroanatomical mapping and computational modelling, based on anatomical, electrophysiological and clinical considerations, with precise definitions of regional borders allowing for reproducible and automated regionalization. 3D imaging and high-resolution electroanatomical mapping have become an integral part of cardiac electrophysiology and the management of patients with arrhythmias. However, to perform regional quantitative analyses and intra- and inter-individual, as well as cross-modality comparisons, a universal definition of atrial regions and their boundaries is required. While for the left ventricle there is already an established standardized regionalization (AHA 17-segment model), there is no such consensus for the atria. In a multi-disciplinary writing group consisting of cardiologists, cardiac electrophysiologists, cardiovascular imaging specialists, and anatomists as well as specialists in computational cardiac modelling from European Heart Rhythm Association and European Association of Cardiovascular Imaging, a standardized regionalization based on a 15-segment bi-atrial model was elaborated. This clinical consensus document will enable consistent regional analyses and homogeneous data acquisition across different centres and modalities, and may thus have a significant impact on atrial arrhythmia research and personalized treatment approaches based on individual arrhythmia patterns and phenotypes.

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.

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.