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Recently, an artifactual horizontal extension of the color Doppler signal was described in patients with mitral regurgitation (MR), called color Doppler splay (CDS). This side-lobe artifact was shown to be associated with concealed and significant MR. In the present study, the authors assessed the prognostic significance of CDS and its hemodynamic correlates.Consecutive patients with primary and secondary MR underwent comprehensive transthoracic echocardiography. Machine settings were fixed for all patients. MR severity was assessed using an integrated approach, as advocated in current international guidelines. The presence of CDS and CDS width and duration were assessed. The outcome measures included the incidence of major adverse cardiac events (a composite of cardiovascular mortality, hospitalization for decompensated heart failure, mitral valve surgery, or percutaneous mitral intervention).One hundred twenty-seven of 469 patients (27%) with MR demonstrated CDS. The presence of CDS was associated with worse MR, and CDS width correlated with effective regurgitant orifice area, regurgitant volume, and vena contracta width. Mitral annular or leaflet calcification was inversely associated with the presence of CDS. Patients with CDS experienced worse event-free survival. For CDS width, a cutoff of29 mm was identified as optimal regarding outcome prediction in our cohort and termed "severe CDS." In multivariate Cox regression, the presence of severe CDS was associated with adverse outcome, independent of MR etiology or severity and other clinical and echocardiographic predictors of outcome, and provided incremental prognostic value on top of these parameters.In patients with MR, the presence of CDS is associated with more severe MR and worse outcomes. Severe CDS provides incremental prognostic value on top of traditional MR metrics and should alert the echocardiographer that MR severity may be underestimated.

Left bundle branch area pacing (LBBAP) has been performed exclusively using lumen-less pacing leads (LLL) with fixed helix design. This registry study explores the safety and feasibility of LBBAP using stylet-driven leads (SDL) with extendable helix design in a multicenter patient population. This study prospectively enrolled consecutive patients who underwent LBBAP for bradycardia pacing or heart failure indications at eight Belgian hospitals. LBBAP was attempted using SDL (Solia S60; Biotronik) delivered through dedicated delivery sheath (Selectra3D). Implant success, complications, procedural, and pacing characteristics were recorded at implant and follow-up. The study enrolled 353 patients (mean age 76 ± 39 years, 43% female). The mean number of implants per center was 25 (range: 5-162). Overall, LBBAP with SDL was successful in 334/353 (94%), varying from 93% to 100% among centers. Pacing response was labeled as left bundle branch pacing in 73%, whereas 27% were labeled as myocardial capture. Mean paced QRS duration and stimulus to left ventricular activation time measured 126 ± 21 ms and 74 ± 17. SDL-LBBAP resulted in low pacing thresholds (0.6 ± 0.4 V at 0.4 ms), which remained stable at 12 months follow-up (0.7 ± 0.3, p = .291). Lead revisions for SDL-LBBAP occurred in 5 (1.4%) patients occurred during a mean follow up of 9 ± 5 months. Five (1.4%) septal coronary artery fistulas and 8 (2%) septal perforations occurred, none of them causing persistent ventricular septal defects. The use of SDL to achieve LBBAP is safe and feasible, characterized by high implant success in low and high volume centers, low complication rates, and stable low pacing thresholds.

A 67-year old female patient with non-ischemic cardiomyopathy and wide (180ms) left bundle branch block (LBBB) and reduced ejection fraction (EF)35% despite optimal medical treatment was referred for cardiac resynchronization therapy (CRT) This article is protected by copyright. All rights reserved.

In patients with heart failure and functional mitral regurgitation (FMR), the assessment of left ventricular (LV) function is important for risk stratification and decision making. As LV ejection fraction (LVEF) might not be an optimal metric for LV systolic performance in this population, alternatives such as global longitudinal strain (GLS) and global myocardial work index (GWI) have been proposed. In the present study, we investigated the prognostic value of GLS and GWI and compared these measures to other LV systolic performance parameters. A prospective and consecutive cohort of 181 patients (median age 72 years, 76% male) with LVEF

Background: Septal strain patterns measured by echocardiography reflect the severity of left bundle branch block (LBBB)-induced left ventricular (LV) dysfunction. We investigated whether these LBBB strain stages predicted the response to cardiac resynchronization therapy in an observational study and developed a sheep model of LBBB-induced cardiomyopathy. Methods: The clinical study enrolled cardiac resynchronization therapy patients who underwent echocardiographic examination with speckle-tracking strain analysis before cardiac resynchronization therapy implant. In an experimental sheep model with pacing-induced dyssynchrony, LV remodeling and strain were assessed at baseline, at 8 and 16 weeks. Septal strain curves were classified into 5 patterns (LBBB-0 to LBBB-4). Results: The clinical study involved 250 patients (age 65 [58; 72] years; 79% men; 89% LBBB) with a median LV ejection fraction of 25 [21; 30]%. Across the stages, cardiac resynchronization therapy resulted in a gradual volumetric response, ranging from no response in LBBB-0 patients (ΔLV end-systolic volume 0 [−12; 15]%) to super-response in LBBB-4 patients (ΔLV end-systolic volume −44 [−64; −18]%) ( P< 0.001). LBBB-0 patients had a less favorable long-term outcome compared with those in stage LBBB≥1 (log-rank P =0.003). In 13 sheep, acute right ventricular pacing resulted in LBBB-1 (23%) and LBBB-2 (77%) patterns. Over the course of 8−16 weeks, continued pacing resulted in progressive LBBB-induced dysfunction, coincident with a transition to advanced strain patterns (92% LBBB-2 and 8% LBBB-3 at week 8; 75% LBBB-3 and 25% LBBB-4 at week 16) ( P =0.023). Conclusions: The strain-based LBBB classification reflects a pathophysiological continuum of LBBB-induced remodeling over time and is associated with the extent of reverse remodeling in observational cardiac resynchronization therapy-eligible patients.

To provide an overview of mitral annular disjunction (MAD) and to discuss important challenges in diagnosis and management of MAD.MAD has regained interest in the context of sudden cardiac death (SCD) in patients with mitral valve prolapse (MVP), coined as the "arrhythmic" MVP syndrome. In addition, MAD in isolation was recently suggested to be associated with severe arrhythmia and SCD. There is a lack of consensus on the definition of MAD and the imaging modality to be used for diagnosing MAD, and the therapeutic implications of MAD remain uncertain. Furthermore, the exact mechanism underlying the association of MAD with SCD remains largely unexplored.

Introduction New-onset left bundle branch block (LBBB) following transcatheter or surgical aortic valve replacement (LBBBAVI) implies a proximal pathogenesis of LBBB. This study compares electrocardiographic characteristics and concordance with LBBB definitions between LBBBAVI and non-procedure-induced LBBB controls (LBBBcontrol). Methods All LBBBAVI patients at Ghent University Hospital between 2013 and 2019 were enrolled in the study. LBBBAVI patients were matched for age, sex, ischaemic heart disease and ejection fraction to LBBBcontrol patients in a 1:2 ratio. For inclusion, a non-strict LBBB definition was used (QRS duration ≥ 120 ms, QS or rS in V1, absence of Q waves in V5-6). Electrocardiograms were digitally analysed and classified according to three LBBB definitions: European Society of Cardiology (ESC), Strauss and American Heart Association (AHA). Results A total of 177 patients (59 LBBBAVI and 118 LBBBcontrol) were enrolled in the study. LBBBAVI patients had more lateral QRS notching/slurring (100% vs 85%, p = 0.001), included a higher percentage with a QRS duration ≥ 130 ms (98% vs 86%, p = 0.007) and had a less leftward oriented QRS axis (−15° vs −30°, p = 0.013) compared to the LBBBcontrol group. ESC and Strauss criteria were fulfilled in 100% and 95% of LBBBAVI patients, respectively, but only 18% met the AHA criteria. In LBBBcontrol patients, concordance with LBBB definitions was lower than in the LBBBAVI group: ESC 85% (p = 0.001), Strauss 68% (p p = 0.035). No differences in electrocardiographic characterisation or concordance with LBBB definitions were observed between LBBBAVI and LBBBcontrol patients with lateral QRS notching/slurring. Conclusion Non-uniformity exists among current LBBB definitions concerning the detection of proximal LBBB. LBBBAVI may provide a framework for more consensus on defining proximal LBBB.

Introduction Left bundle branch area pacing (LBBAP) aims to achieve physiological pacing by capturing the conduction system in the area of the left bundle branch. LBBAP has exclusively been performed using lumen-less pacing leads (LLLs) with fixed helix design. This study explores the feasibility, safety, and pacing characteristics of LBBAP using stylet-driven leads (SDLs) with an extendable helix design. Methods Patients, in which LBBAP was attempted for bradycardia or heart failure pacing indications, were prospectively enrolled at the Ghent University Hospital. LBBAP was attempted with two different systems: 1/LLL with fixed helix (SelectSecure 3830, Medtronic Inc.) delivered through a preshaped sheath (C315His Medtronic Inc.) and 2/SDL with extendable helix (Solia S60, Biotronik, SE & CO) delivered through a new delivery sheath (Selectra 3D, Biotronik). Results The study enrolled 50 patients (mean age: 70 +/- 14 years, 44% females). LBBAP with SDL was successful in 20/23 (87%) patients compared with 24/27 (89%) of patients in the LLL group (p = 0.834). Screw attempts, screw implant depth, procedural, and fluoroscopy times were comparable among both groups. Acute LBBAP thresholds were low and comparable between SDL and LLL (0.5 +/- 0.15 V vs. 0.4 +/- 0.17 V, p = 0.251). Pacing thresholds remained low at 3 +/- 2.1 months of follow up in both groups and no lead revisions were necessary. Postprocedural echocardiography revealed a septal coronary artery fistula in one patient with SDLLBBAP. Conclusion LBBAP using stylet-driven pacing leads is feasible and yields comparable implant success to LBBAP with LLLs. LBBAP thresholds are low and comparable with both types of leads.

His bundle pacing (HBP) offers physiologic pacing by placing the pacing lead directly to the His bundle. We present a case in which a HBP lead, implanted at the fragile membranous septum, resulted in a persistent restrictive perimembranous ventricular septal defect (VSD). This complication of HBP has not been reported before but brings new insights in the discussion regarding the optimal position of a pacing lead in the ventricular septum. The fragility of the membranous septum and low rate of spontaneous closure of membranous VSD, might favor lead placement in the muscular septum when aiming for physiologic pacing.

New-onset left bundle branch block (LBBB) is a frequent complication after transcatheter aortic valve replacement (TAVR) and provides an opportunity to study dyssynchrony immediately following acute LBBB. This study aims to (1) assess echocardiographic dyssynchrony in acute TAVR-induced LBBB (TAVR-LBBB), and (2) compare dyssynchrony parameters among different patient groups with LBBB. The study enrolled all TAVR-LBBB patients at Ghent University Hospital between 2013 and 2019. First, acute TAVR-LBBB dyssynchrony was assessed by: (1) septal flash (SF); (2) interventricular mechanical delay (IVMD; cut-off ≥ 40 ms) and (3) presence of ‘classical dyssynchronous strain pattern’ assessed with speckle tracking. Secondly, acute TAVR-LBBB patients with SF (LBBBTAVR+SF) were compared to randomly selected LBBB-SF patients with preserved (LBBBSF+PEF) and reduced ejection fraction (LBBBSF+REF). In TAVR-LBBB patients (n = 25), SF was detected in 72% of patients, whereas only 5% of TAVR-LBBB patients showed a classical dyssynchronous strain pattern. IVMD in these TAVR-LBBB patients was 39 ms. In 90% of LBBBTAVR+SF patients, SF was observed within 24 h after LBBB onset. Among LBBB-SF patients, a classical strain pattern was more prevalent in LBBBSF+REF patients compared to LBBBTAVR+SF patients (80% vs. 7%; p

Background Mitral regurgitation (MR) is a frequent consequence of mitral valve prolapse (MVP). However, the echocardiographic grading of MR is challenging, and the recommended grading parameters have several limitations. The authors developed a novel echocardiographic parameter to grade MR, the average pixel intensity (API) method, on the basis of pixel intensity analysis of the continuous-wave Doppler signal. Methods Transthoracic echocardiography was performed prospectively in consecutive patients with MVP (N = 149). MR was quantitatively assessed using the API method, vena contracta width, effective regurgitant orifice area, and regurgitant volume. The primary clinical events were cardiovascular mortality, mitral valve surgery, percutaneous mitral intervention, and heart failure hospitalization. Results The API method was feasible in 90% of all patients with MVP, which was significantly higher than vena contracta width, effective regurgitant orifice area, and regurgitant volume. During a median follow-up period of 17 months, 44 patients (32%) had major adverse cardiac events, and the majority of events occurred in the holosystolic MVP subgroup. The degree of MR severity by the API method was highly significant for the prediction of events. An API cutoff of 111 arbitrary units was defined as “severe” MR due to MVP, with overall superior sensitivity and specificity compared with cutoffs for established MR grading parameters. In patients who did not have major adverse cardiac events during the follow-up period (n = 92), no significant changes in measures of MR severity were found on follow-up echocardiography. Conclusions The API method is predictive of clinical events and outcomes in MR due to MVP. Therefore, the API method may be considered for grading the severity of MR due to MVP in clinical practice.

Graphical abstract, Highlights • Near field clutter (NFC) is a frequently encountered ultrasound artifact. • NFC was previously attributed to high amplitude oscillations of the transducer itself. • Near field artifacts are caused by reverberation with or without refraction. • We propose approaches to differentiate a NFC from a true mass or thrombus.

Graphical abstract, Highlights • Drug-induced valvular heart disease (DI-VHD) is reminiscent of carcinoid heart disease. • DI-VHD is mediated through 5-hydroxytryptamine 2β receptor signaling pathways. • Serotonergic agents interacting with this 2β receptor may cause carcinoid-like VHD. • DI-VHD must be considered in patients with no reasons for showing VHD and using SSRI. • Echocardiographic surveillance is warranted in patients on serotonergic drugs, including SSRI.

Introduction Recent cross-sectional studies suggest a relationship between persisting left bundle branch block (LBBB) and the extent of left ventricular (LV) electro-mechanical alterations over time. When patients are referred for cardiac resynchronization therapy (CRT), temporal data during the sub-clinical phase of disease is often missing. A longitudinal study using an animal model would provide a better understanding of the relationship between the onset of LBBB and the electro-mechanical changes. Purpose To investigate the sequential alterations in LV structure and function that develop over time in an animal model of LBBB. Methods Thirteen sheep were subjected to rapid DDD pacing (180 bpm; leads on right atrium and right ventricular free wall) in order to induce a LBBB-like conduction delay. All animals underwent an 8-week pacing protocol, whereas 4 of them were subjected to 16 weeks of pacing in total. Echocardiographic speckle tracking was used to assess circumferential strain of the septal and lateral wall. Septal and lateral wall thickness were measured at end-diastole. Cardiac magnetic resonance imaging was used to determine LV volumes and ejection fraction (LVEF). Examinations took place at baseline (before and after start of pacing), and after 8 and 16 weeks of pacing. All examinations were performed at a physiologic heart rate of 110 bpm. Results At baseline, DDD pacing induced an increase in QRS duration (+85%, p0.05). After 8 weeks of DDD pacing, mechanical dyssynchrony worsened: septal notching increased, followed by reduced systolic shortening. After 16 weeks, the initial septal shortening was followed by profound stretching throughout systole. Lateral wall systolic shortening was reduced compared to baseline. QRS duration increased further by +12% (week 8) and +20% (week 16) (all p Conclusion A persisting LBBB-like conduction delay induces sequential changes in LV deformation patterns, and triggers morphological and electrical remodelling. These changes are similar to those observed in patients with LBBB and different degrees of LV dysfunction. Our data suggest a continuum due to the progression of LBBB-induced LV disease. In the clinic, patients with mild dysfunction should be closely monitored in order to treat dyssynchrony as soon as guideline indications are reached. Funding Acknowledgement Type of funding sources: Other. Main funding source(s): This work was supported by a KU Leuven research grant

IMPORTANCE: Mitral annular disjunction (MAD) has received particular interest in patients with mitral valve prolapse, ventricular tachycardia, and sudden cardiac death. The clinical significance of MAD for patients with Marfan syndrome (MFS) remains largely unexplored. OBJECTIVE: To define the prevalence of MAD and examine its association with cardiovascular outcomes and arrhythmia among patients with MFS. DESIGN, SETTING, AND PARTICIPANTS: This retrospective, single-center cohort study included 142 patients with a diagnosis of MFS based on the revised Ghent criteria and a confirmed (likely) pathogenic variant in the FBN1 gene who underwent regular follow-up between January 1, 2004, and December 31, 2019. MAIN OUTCOMES AND MEASURES: The presence of MAD was assessed by echocardiography, and the extent of MAD was categorized in tertiles. Patients also underwent resting electrocardiography and 24-hour Holter monitoring. Outcomes included aortic events (aortic dissection or prophylactic aortic surgery), arrhythmic events (defined as sustained ventricular tachycardia or sudden cardiac death), and mitral valve surgery. RESULTS: A total of 142 patients (72 female patients [51%]; median age at first examination, 25 years [range, 2-64 years]) were evaluated. Forty-eight patients (34%) had MAD. Patients with MAD had larger aortic root z scores than patients without MAD (4.1 [interquartile range, 2.8-5.7] vs 3.0 [interquartile range, 1.8-4.0]; P 10 mm) showed a higher occurrence of aortic events compared with patients with MAD of 10 mm or smaller (9 of 15 [60%] vs 6 of 28 [21%]; P = .01). Patients with arrhythmic events (n = 5) and patients requiring mitral valve surgery (n = 7) were observed exclusively in the group displaying MAD. CONCLUSIONS AND RELEVANCE: This study suggests that MAD among patients with MFS is associated with the occurrence of arrhythmic events, a higher need for mitral valve intervention, and, among patients with extensive MAD, more aortic events. Cardiac imaging for patients with MFS should consider the assessment of MAD as a potential marker for adverse outcomes.

The low-n attenuated phase-shift mask can strongly improve extreme ultraviolet imaging performance; it enhances contrast by mask 3D mitigation and a phase-shift effect while simultaneously reducing the required exposure dose. The latter happens because the low-n mask gives optimum contrast at more open mask bias values than its Ta-based counterpart. Here, we experimentally verify the imaging physics of the low-n mask. We show that optimum exposure latitude (EL) with the low-n mask is obtained at more open mask bias values compared to the Ta-based reference mask. This leads to dose reductions exceeding 30% for pitch 38-nm regular contact holes (CHs). Initial local critical dimension uniformity (LCDU) data for hexagonal CHs pitch 38 and 40 nm show 15% LCDU improvement with the low-n mask compared to the Ta-based reference. A 16-nm dense lines show a substantial EL increase and dose reduction with the low-n mask compared to the Ta-based case; this can be even further improved by combining the novel mask absorber with asymmetric illumination. As the low-n masks studied here have absolute reflectivities in the range 8% to 15%, side-lobe printing should be carefully monitored. Initial experimental data for pitch 120-nm CHs and simulations on P32 metal clips, show no signs of side-lobe printing. Careful monitoring of stochastic side-lobe printing for various use cases is recommended.

Previously we introduced and validated the average pixel intensity (API) method for grading mitral regurgitation (MR) in a heterogeneous MR population. We now investigated the feasibility and added value of the API method more specifically in patients with functional MR (FMR). We consecutively enrolled 283 patients with pure FMR. Transthoracic echocardiography was performed and MR was assessed using the API method and guideline-recommended parameters, including color Doppler, vena contracta width (VCW) and proximal isovelocity surface area (PISA)-based methods. The API method had an applicability of 98% in this FMR cohort, which was significantly higher than VCW (84%) and PISA-based methods (75%). Overall, the API method had significant correlations with direct parameters of FMR severity, ejection fraction, atrial and ventricular dimensions, pulmonary pressures and New York Heart Association class. Analysis of the API dynamics during MR revealed a typical pattern with early and late systolic peaks in API and a midsystolic nadir, which matched the temporal changes of the effective regurgitant orifice (ERO) during FMR. Based on ROC curves of established FMR severity cut-offs, an API value of 125 au was considered the optimal cut-off to determine severe MR. Interestingly, this API severity cut-off is similar to the API severity cut-off for MR in degenerative MR (DMR), despite different EROA/RV cut-offs in current ESC guidelines for FMR and DMR. The API method is an easy, fast and feasible parameter for grading FMR and may complement the multiparametric assessment of FMR in daily clinical practice.

Today’s EUV masks are optimized for maximum reflectivity at 6o angle of incidence to support imaging on the 0.33NA scanners. The High-NA EUV scanner will have an NA of 0.55 and anamorphic optics, as right balance between productivity and keeping the angles on mask level compatible with the current EUV masks. However, for selected use-cases increased Mask-3D effects are observed. The enlarged angular spread on mask for vertical L/S may cause, amongst others, an increased non-telecentricity variation across slit compared to 0.33NA, potentially leading to on-product overlay errors. In this paper, we will show the root-cause of these enhanced M3D effects for High-NA EUV and the role of the EUV mask multilayer. We will show how an ideal EUV multilayer could look like to mitigate these M3D effects and propose a practical embodiment in the form of a RuSi multilayer stack. We will show some first experimental results of an ion beam deposited RuSi test sample, assess the main challenges from manufacturability point of view and what imaging performance can be expected for such a mask multilayer applied for High-NA EUV.

This study speculated that longitudinal strain curves in left bundle branch block (LBBB) could be shaped by the degree of LBBB-induced cardiac remodeling.LBBB independently affects left ventricular (LV) structure and function, but large individual variability may exist in LBBB-induced adverse remodeling.Consecutive patients with LBBB with septal flash (LBBB-SF) underwent thorough echocardiographic assessment, including speckle tracking-based strain analysis. Four major septal longitudinal strain patterns (LBBB-1 through LBBB-4) were discerned and staged on the basis of: 1) correlation analysis with echocardiographic indexes of cardiac remodeling, including the extent of SF; 2) strain pattern analysis in cardiac resynchronization therapy (CRT) super-responders; and 3) strain pattern analysis in patients with acute procedural-induced LBBB.The study enrolled 237 patients with LBBB-SF (mean age: 67 ± 13 years; 57% men). LBBB-1 was observed in 60 (26%), LBBB-2 in 118 (50%), LBBB-3 in 29 (12%), and LBBB-4 in 26 (11%) patients. Patients at higher LBBB stages had larger end-diastolic volumes, lower LV ejection fractions, longer QRS duration, increased mechanical dyssynchrony, and more prominent SF compared with less advanced stages (p 0.001 for all). Among CRT super-responders (n = 30; mean age: 63 ± 10 years), an inverse transition from stages LBBB-3 and -4 (pre-implant) to stages LBBB-1 and -2 (pace-off, median follow-up of 66 months [interquartile range: 32 to 78 months]) was observed (p 0.001). Patients with acute LBBB (n = 27; mean age: 83 ± 5.1 years) only presented with a stage LBBB-1 (72%) or -2 pattern (24%).The proposed classification suggests a pathophysiological continuum of LBBB-induced LV remodeling and may be valuable to assess the attribution of LBBB to the extent of LV remodeling and dysfunction.

Next-generation extreme ultraviolet (EUV) systems with numerical apertures of 0.55 have the potential to provide sub-8-nm half-pitch resolution. The increased importance of stochastic effects at smaller feature sizes places further demands on scanner and mask to provide high contrast images. We use rigorous mask diffraction and imaging simulation to understand the impact of the EUV mask absorber and to identify the most appropriate optical parameters for high NA EUV imaging. Simulations of various use cases and material options indicate two main types of solutions: high extinction materials, especially for lines spaces, and low refractive index materials that can provide phase shift mask solutions. EUV phase masks behave very different from phase shift masks for DUV. Carefully designed low refractive index materials and masks can open up a new path toward high contrast edge printing.

To enable failure-free process windows with EUV lithography a sufficiently high optical contrast is required. For decreasing pitch the contrast requirements may only be achieved with advanced masks such as, high-k and attenuated PSM. While manufacturing high-k absorbers requires effort, the imaging theory is straightforward. Studies to the PSM have shown even better image contrast, at the cost of increased complexity of the imaging theory. The strong presence of M3D effects with EUV drives the attenuated PSM imaging physics in a different direction than for DUV. We report on the investigation of the expected requirements and capabilities of the PSM

Left bundle branch area pacing (LBBAP) is a novel pacing technique that requires the pacing lead to be screwed through the septum toward the left side of the interventricular septum ([1][1]). An 84-year-old woman underwent LBBAP for third-degree atrioventricular block. LBBAP was performed with a 5.6

INTRODUCTION The electrocardiographic (ECG) pattern of true left bundle branch block (LBBB) has not been fully clarified and various definitions of LBBB exist. New-onset LBBB after transcatheter (TAVR) or surgical (SAVR) aortic valve replacement implies a proximal pathogenesis of LBBB and thus may provide a reference to characterize and define true LBBB. PURPOSE This study compares ECG characteristics in aortic valve implantation-induced LBBB (AVI-LBBB) to a non-procedural-induced LBBB control group (co-LBBB) in order to set a more homogenous definition for true LBBB. METHODS The study enrolled all patients with new-onset TAVR- and SAVR-induced LBBB between 2013 and 2019. AVI-LBBB was defined as new-onset persistent LBBB occurring within 24h after TAVR or SAVR. Patients were matched for age, sex, ischemic heart disease and left ventricular systolic function to randomly selected co-LBBB patients in a 1:2 ratio. For inclusion in both groups, a non-strict LBBB definition was used (QRSD ≥120ms, QS or rS in lead V1, absence of Q wave in leads V5-6). ECG characteristics were digitally analysed by the MUSE algorithm and confirmed by two experts. All ECG recordings were classified according to 4 different LBBB definitions: MADIT, European Society of Cardiology (ESC), Strauss and American Heart Association (AHA). RESULTS 59 patients with AVI-LBBB (34 TAVR, 25 SAVR, median age 82 years, 42% male) were compared to 118 matched co-LBBB patients. All patients with AVI-LBBB presented with QRS notching/slurring in the lateral leads, whereas this was present in only 85% of the co-LBBB group (p = 0.001). QRS duration (148ms vs 145ms, p = 0.074) and R wave peak time (58ms vs 62ms, p = 0.065) were not significantly different among both groups. AVI-LBBB was characterized by a more rightward QRS axis (-15° vs -30°, p = 0.013). When comparing AVI-LBBB to LBBB controls with QRS notching/slurring, a comparable QRS axis was observed. Almost all AVI-LBBB patients met the MADIT (98%), ESC (100%) and Strauss (95%) definition. Only 18% of patients met the AHA definition, because of the low combined presence of QRS notching/slurring in all 4 lateral leads (54%) and because only 27% of patients had an R wave peak time >60ms in both leads V5-6. In the co-LBBB group, adherence to the different definitions was significantly lower compared to the AVI-LBBB group: MADIT 86% (p = 0.007), ESC 85% (p = 0.001), Strauss 68% (p CONCLUSIONS Discordance exists between various definitions in scoring AVI-LBBB. Our data show that presence of QRS notching/slurring in the lateral leads is a crucial feature of proximal LBBB, rather than QRS duration and R wave peak time. The AVI-LBBB population provides a framework towards a more uniform definition and criteria for assessing true, proximal LBBB.

Recent randomised percutaneous mitral intervention trials in patients with heart failure with secondary mitral regurgitation (SMR) have yielded contrasting results. A ‘relative load’ or ‘proportionality’ conceptual framework for SMR has been proposed to partly explain the disparate results. The rationale behind the framework is that SMR depends on the left ventricular dimension and not vice versa. In this review, we provide an in-depth analysis of the proportionality parameters used in this framework and also discuss the regurgitant fraction. We also consider haemodynamic observations in SMR that may affect the interpretation and comparisons among proportionality parameters. The conclusion is that the proportionality concept remains hypothetical and requires prospective validation before envisaging its use at individual patient level for risk stratification or therapeutic decision-making.

Pushing the novel anamorphic NA=0.55 EUV projection optics to k1 values below 0.4 and to its ultimate resolution limit will require an alternative mask absorber stack. This paper describes the application of rigorous imaging simulations in combination with multi-objective optimization to access the performance of novel absorber materials for the NA=0.55 system. Simulations of various use cases and material options indicate two main types of solutions: high k materials (k>0.05, especially for vertical lines/spaces) and low n materials (n ~ 0.9) to provide phase shift mask solutions for contact arrays.

Recent MitraClip heart failure (HF) trials suggest that baseline left ventricular (LV) remodeling may be critical for patient selection. We, therefore, investigated whether base-line LV remodeling affects safety, efficacy, and clinical outcomes in HF patients with symptomatic secondary mitral regurgitation (MR) undergoing percutaneous mitral valve repair using MitraClip. LV remodeling was assessed by LV end-systolic dimension index (LVESDi) on transthoracic baseline echocardiography. Early and late outcome was reported using Mitral Valve Academic Research Consortium-criteria. A total of 107 consecutive HF patients (73 +/- 10 years, 70% male) who underwent MitraClip intervention for secondary MR were studied. The study population was stratified by median LVESDi between nonadvanced (= 28 mm/m(2), n = 58). Both groups had similar acute procedural success, in hospital bleeding and nonbleeding complications and significant improvement in MR severity and symptoms, sustained up to 36 months (all p >0.05). LVESDi, but not LV end-diastolic diameter index nor LV ejection fraction, independently related to HF hospitalization (hazard ratio 1.11, 95% confidence interval 1.05 to 1.16, p

Background Mitral valve prolapse (MVP) is a common cause of chronic mitral regurgitation (MR). Barlow’s disease (BD) and fibro-elastic deficiency (FED) are two major entities of MVP affecting the connective tissue of the mitral valve, but both have a different underlying pathophysiology and phenotype. In some connective tissue diseases (CTD), it has been suggested that ventricular dysfunction occurs despite absence of MR, suggesting that CTD directly involve the myocardium. We therefore investigated whether patients with BD have different cardiac dimensions compared to FED, after correcting for MR severity grade. Methods 134 patients with MVP and chronic MR were prospectively included. MR was graded carefully by echocardiography using a multi-parametric approach. The morphology of the mitral valve prolapse was specified as definite Barlow (n = 45) or non-Barlow (n = 89; FED, flail leaflet or unspecified etiology) by two experienced echocardiographers. Results In our cohort, MR was significantly more severe in the non-Barlow group compared to typical BD group (regurgitant volume (RV) 51 vs 33 ml, p = 0.021; right ventricular systolic pressure, 40 vs 34 mmHg, p= 0.05, left atrial volume index, 51 vs 42 ml/m², p = 0.07, respectively). However, there was a trend towards higher left ventricular end-diastolic diameter index (LVEDDi, 27.7 vs 29 mm, p = 0.07) and a significantly higher end-diastolic volume index (LVEDVi, 62 vs 71 ml/m², p= 0.02) in the Barlow group, despite similar ejection fractions and much less MR in the Barlow group. This resulted in a significantly higher RV/LVEDV ratio in the non-Barlow group compared to the Barlow group (42% vs 23%, p = 0.001). Similarly, the LA volume/LVEDV ratio was significantly lower in the Barlow cohort (63 vs 79%, p= 0.026). There were no significant differences in aortic dimensions between groups. Conclusions We describe for the first time that compared to non-Barlow (mostly FED), patients with MVP due to typical Barlow disease have larger ventricular dimensions and volumes, which are disproportionate to the degree of MR. We therefore hypothesize that the connective tissue alterations in these patients may also involve the myocardium resulting in LV dilation independent of MR. Further investigation and clinical implications of these findings is mandatory.

Background Dynamic changes in functional mitral regurgitation (FMR) during exercise echocardiography were shown to be of prognostic value. However grading of FMR is challenging, especially during exercise echocardiography and therefore questioning its applicability in clinical practice. We recently introduced and validated the Average Pixel Intensity (API) for grading MR based on the pixel intensity of the continuous wave Doppler signal. In the current study we investigate the use of the API method using leg lift and exercise echocardiography in FMR. Methods We prospectively included 50 heart failure patients (mean ejection fraction 36%) in sinus rhythm with different grades of pure, FMR. After assessment of FMR severity at rest, the same acquisitions were repeated during leg lift and exercise echocardiography. FMR was assessed using the API method, color Doppler and quantitative grading methods (proximal isovelocity surface area (PISA) and vena contracta width (VCW)). Results The API method could be performed in all patients (100%) with leg lift (n = 50) and in 94% of the patients undergoing exercise echocardiography (n = 44), which was more than PISA and VCW (p During leg lift, there was a small but significant increase on visual color Doppler grading (grade 1.93 to 2.11 (p = 0.004); increase of FMR in 35% of patients, and no difference in 65%). For API, we found the same significant increase (93 to 101 au), however, API values showed increase of MR in 62% and decrease of FMR in 20%. During exercise echocardiography, we found no differences in color Doppler grade and API in the overall cohort (p 0.252 and p 0.832, respectively), despite 62% of patients showing some degree of increase in API during leg lift. On multivariate analysis, no specific echo parameter could be identified as independent predictor of API increase. Conclusions The novel API method is highly feasible for assessing dynamic FMR and may be of added value for in this setting, allowing the detection of even small increments of FMR severity. In the current study, we found only mild increases of FMR during exercise echocardiography. Leg lift testing however proved to be a simple and quick loading approach that induced a significant rise in FMR compared to exercise echocardiography. The prognostic relevance of the findings during leg lift remains to be determined.

Cardiac resynchronization therapy (CRT) has been a major step in the treatment of heart failure patients and intraventricular conduction delay. As a considerable number of patients do not respond adequately to CRT, echocardiographic dyssynchrony selection criteria have been proposed to improve CRT response, but these parameters eventually failed to provide superior selection of CRT candidates. In the last decade, an echo-dyssynchrony parameter called "septal flash" was been reported by several investigators and opinion leaders in the field of CRT. This parameter has a strong pathophysiological rationale and was shown to be a robust and predominant predictor of CRT response in recent observational and retrospective studies. We here provide a comprehensive and balanced overview of septa! flash and address several important aspects, questions and potential future implications of septal flash in cardiomyopathy and CRT. (C) 2019 The Authors. Published by Elsevier Inc.

Background: Complete left bundle branch block (cLBBB) is associated with increased cardiovascular mortality and heart failure. On the contrary, the clinical relevance of incomplete left bundle branch block (iLBBB) is less known. This study investigated the profile and outcome of iLBBB patients and assessed the risk of progression to cLBBB. Methods: Patients diagnosed with iLBBB between July 2013 and April 2018 were retrospectively included. Subsequently, echo- and electrocardiographic examinations at time of iLBBB diagnosis and during follow-up, as well as progression to non-strict cLBBB and strict cLBBB, were evaluated. Results: The study enrolled 321 patients (33% female, age 74 +/- 11 years). During the follow-up of 21 (8;34) months, 33% of iLBBB patients evolved to non-strict cLBBB and 27% to strict cLBBB. iLBBB patients who evolved to non-strict or strict cLBBB were older, had more frequently reduced left ventricular ejection fraction, and had more often QRS notching/slurring in the lateral leads and inferior leads, compared to patients without progression to cLBBB. In multivariate analysis, only QRS notching/slurring in the lateral leads was independently associated with progression to non-strict cLBBB (odds ratio 4.64, p < .001) and strict cLBBB (odds ratio 9.6, p < .001). iLBBB patients with QRS notching/slurring had a progression rate to non-strict cLBBB of 52% and 49% to strict cLBBB. Conclusion: Among patients with iLBBB, up to one third of the patients progress to cLBBB within a period of 2 years. The presence of QRS notching/slurring in the lateral leads during iLBBB was the strongest predictor for progression toward cLBBB.

Background Conduction disorders requiring permanent pacemaker implantation occur frequently after transcatheter aortic valve replacement (TAVR). This multicenter study explored the feasibility and safety of His bundle pacing (HBP) in TAVR patients with a pacemaker indication to correct a TAVR‐induced left bundle branch block (LBBB). Methods Patients qualifying for a permanent pacemaker implant after TAVR were planned for HBP implant. HBP was performed using the Select Secure (3830; Medtronic) pacing lead, delivered through a fixed curve or deflectable sheath (C315HIS or C304; Medtronic). Successful HBP was defined as selective or nonselective HBP, irrespective of LBB recruitment. Successful LBBB correction was defined as selective or nonselective HBP resulting in paced QRS morphology similar to pre‐TAVR QRS and paced QRS duration (QRSd) less than 120 milliseconds with thresholds less than 3.0 V at 1.0‐millisecond pulse width. Results The study enrolled 16 patients requiring a permanent pacemaker after TAVR (age 85 ± 4 years, 31% female, all LBBB; QRSd: 161 ± 14 milliseconds). Capture of the His bundle was achieved in 13 of 16 (81%) patients. HBP with LBBB correction was achieved in 11 of 16 (69%) and QRSd narrowed from 162 ± 14 to 99 ± 13 milliseconds and 134 ± 7 milliseconds during S‐HBP and NS‐HBP, respectively (P = .005). At implantation, mean threshold for LBBB correction was 1.9 ± 1.1 V at 1.0 millisecond. Thresholds remained stable at 11 ± 4 months follow‐up (1.8 ± 0.9 V at 1.0 millisecond, P = .231 for comparison with implant thresholds). During HBP implant, one temporary complete atrioventricular block occurred. Conclusion Permanent HBP is feasible in the majority of patients with TAVR requiring a permanent pacemaker with the potential to correct a TAVR‐induced LBBB with acceptable pacing thresholds.

Background Female patients are underrepresented in cardiac resynchronization therapy (CRT) trials, although they show better CRT response compared to males and at shorter QRS durations. We hypothesized that differences in left bundle branch block (LBBB) characteristics and mechanical dyssynchrony might explain this gender disparity. Methods Patients presenting with true LBBB-morphology (including mid-QRS notching) on surface electrocardiograms (ECG) were selected. LBBB QRS duration (QRSD LBBB ) was measured automatically on the ECG. Left ventricular dimensions were assessed by two-dimensional echocardiography. Mechanical dyssynchrony was assessed by the presence of septal flash (SF) on echocardiography. Results The study enrolled 1037 patients (428 females). Female LBBB patients had smaller QRSD LBBB compared to male LBBB patients (142 [22]ms versus 156 [24]ms, p EDD ) were independent predictors of QRSD LBBB . QRSD LBBB can be corrected for sex and LV EDD using a simplified formula: corrected-QRSD LBBB =QRSD LBBB +0.5×(50−LV EDD )−10 (if male). SF was more prevalent in females compared to males (60% versus 43%, p LBBB groups compared to men: 65% versus 13% ( p LBBB 120–129ms, 66% versus 18% ( p LBBB 130–139ms and 63% versus 31% (p LBBB 140–149ms. At QRSD LBBB >150ms, there were no differences in SF prevalence between females and males. Conclusion Female patients show true LBBB morphology at shorter QRSD and have more frequent mechanical dyssynchrony at shorter QRSD compared to males. This might explain the better CRT response rates at shorter QRSD in females.

We read with great interest the papers by Bartko et al. ([1][1]) and Gorcsan et al. ([2][2]) on the predictive value of dyssynchrony markers for cardiac resynchronization therapy (CRT) response, irrespective of the presence of left bundle branch block (LBBB). In the first study, Bartko et al. ([

Introduction: Vectorcardiographic (VCG) QRS area of left bundle branch block (LBBB) predicts acute hemodynamic response in cardiac resynchronization therapy (CRT) patients. We hypothesized that changes in QRS area occurring with biventricular pacing (BV) might predict acute hemodynamic CRT response (AHR). Methods and Results: VCGs of 624 BV paced electrocardiograms (25 LBBB patients with 35 different pacing configurations) were calculated according to Frank's orthogonal lead system. Maximum QRS vector amplitudes (X-Ampl, Y-Ampl, Z(Ampl), and 3D(Amp)) and QRS areas (X-Area, Y-Area, Z(Area), and 3D(Area)) in the orthogonal leads (X, Y, and Z) and in 3-dimensional projection were measured. Volume of the 3D vector loop and global QRS duration (QRSD) on the surface electrocardiogram were assessed. Differences (Delta) in VCG parameters between BV paced and LBBB QRS complexes were calculated. An increase of 10% in dP/dt max was considered as AHR. LBBB conduction is characterized by a large Z(Area) (109 mu Vs, interquartile range [ IQR]: 75; 135), significantly larger than X-Area (22 mu Vs, IQR: 10; 57) and Y-Area (44 mu Vs, IQR: 32; 62, P< 0.001). Overall, QRS duration, amplitudes, and areas decrease significantly with BV pacing (P

BackgroundEchocardiographic grading of secondary mitral regurgitation (SMR) severity is challenging and involves multiple guideline-recommended parameters. We previously introduced the average pixel intensity (API) method for grading SMR. In this study, the clinical outcome in SMR based on the API method for grading MR was compared with conventional grading methods.Methods231 patients with systolic heart failure and reduced ejection fraction (ischaemic/non-ischaemic) and SMR were prospectively enrolled. MR was graded using all guideline-recommended parameters and the API method, which is based on the pixel intensity of the continuous wave Doppler signal. The primary outcome was MACE (major adverse cardiac event).ResultsThe API method was applicable in 98% of patients with SMR (n=227). During a median follow-up of 24 months, 98 patients (43%) had a MACE (cardiovascular mortality (n=50, 22%), heart failure hospitalisation (n=44, 19%), mitral valve surgery (n=11, 5%), percutaneous mitral intervention (n=12, 5%), heart transplantation (n=5, 2%)). On log-rank test, the API method was highly significant in predicting clinical outcome. On multivariable Cox proportional hazard analysis, SMR grading with the API method was an independent predictor of clinical outcome (along with NYHA class and right ventricular systolic pressure; pConclusionSMR grading with the API method is an independent predictor of clinical outcome and provides prognostic information in addition to clinical and other echocardiographic variables.

BACKGROUND Primary mitral valve regurgitation (MR) is a comprehensive term that mostly comprises mitral valve prolapse (MVP), while other causes of degenerative MR are often not considered. We describe the echocardiographic characteristics of degenerative nonprolapse mitral regurgitation (DMR) and assess the outcome at medium-term follow-up using the novel average pixel intensity (API) method. METHODS Of 126 patients with any nonprolapse DMR were consecutively included. MR was graded according to all guideline-recommended parameters and with the API method. MR flow dynamics in DMR were compared to MVP-MR and functional MR (FMR). RESULTS DMR is associated with moderate-to-severe calcifications of the mitral valve apparatus, and a low event rate was observed at a mean follow-up of 27 months. The API grading method had a higher feasibility (94%) compared to proximal isovelocity surface area (PISA) (60%) method and vena contracta width (VCW) (71%) for assessing MR. The API method was predictive for events. The API method also provides insights into DMR flow dynamics: A triphasic pattern was observed with a midsystolic nadir for both API and PISA-EROA, which is similar to the dynamic flow pattern described in FMR, but distinct from holosystolic MVP-MR. Compared to FMR and MVP-MR patients, DMR is less severe and patients with DMR are generally older than MVP-MR patients. CONCLUSIONS DMR is a distinct MR pathology and conveys a relatively low event rate. MR grading was feasible with the API method, and flow dynamics demonstrated a similar triphasic pattern compared to FMR but distinct from holosystolic MVP-MR.

Background Left bundle branch block (LBBB) occurs frequently after transcatheter aortic valve replacement (TAVR) and is associated with increased risk of permanent pacemaker implantation, heart failure hospitalization and sudden cardiac death. This pilot study explored the feasibility of TAVR-induced LBBB correction with His bundle pacing (HBP). Methods Patients with TAVR -induced LBBB and postoperative need for permanent pacemaker implant were planned for electrophysiology study and HBP. Patients with persistent high degree AV-block were excluded. HBP was performed using the Select Secure pacing lead, delivered through a fixed curve or a deflectable sheath. Successful HBP was defined as correction of LBBB by selective or non-selective HBP with LBBB correction thresholds less than 3.5V at 1.0ms at implant. Results The study enrolled 6 patients (mean age 85±2.5 years, 50% male). Mean QRS duration was 152±10ms, PR-interval 212±12ms AH-interval 166±16ms and HV-interval 62±12ms. Successful HBP was achieved in 5/6 (83%) patients. Mean QRS duration decreased from 153±11ms to 88±14ms (p=0.002). At implantation, mean threshold for LBBB correction was 1.6±1.0V (unipolar) and 2.2±1.3V (bipolar) at 1.0ms. Periprocedural, two complete AV-blocks occurred, both spontaneously resolved by the end of the procedure. Thresholds remained stable at 1 month follow up: 1.8±1.0V (unipolar) and 2.3±1.5V (bipolar) at 1.0ms. Figure 1 Conclusion Permanent His bundle pacing can safely correct TAVR-induced LBBB in the majority of patients. Further studies are needed to assess potential benefits of His bundle pacing over conventional right ventricular pacing in this population.

Background Functional mitral regurgitation (FMR) is a frequent finding in patients with systolic heart failure. However, the echocardiographic grading of MR is challenging and different severity cut-offs are recommended by international guidelines. We developed and validated a novel echocardiographic parameter to grade MR, the average pixel intensity (API) method, based on pixel intensity analysis of the continuous wave Doppler signal. Purpose In this study, we assessed the long-term predictive value of the API method on clinical endpoints in FMR. Methods Transthoracic echocardiography was performed in consecutive heart failure patients with reduced EF (HF-REF) (n=221). MR was assessed using the API method, vena contracta width (VCW), effective regurgitant orifice area (PISA-EROA) and regurgitant volume (PISA-RV). The primary clinical events were major adverse cardiac events (MACE: cardiovascular mortality, mitral valve surgery, percutaneous mitral intervention or heart failure hospitalization). Results The API method was feasible in 97% of all FMR patients, which was significantly higher than parameters such as VCW, PISA-EROA and PISA-RV. 84 patients (37%) had one or more clinical events during the follow-up period (cardiovascular mortality (20%), mitral valve surgery (5%), percutaneous mitral intervention (5%), heart failure hospitalization (16%) or heart transplantation (2%)). Based on ROC curves, an API cut-off of 121 au was defined as “severe” MVP-MR with an overall better sensitivity and specificity than current guideline-recommended parameters. On multivariate analysis, MR graded with API was independently predictive for clinical events, whereas PISA-based methods were not independent. In addition, pulmonary pressures and NYHA class were powerful independent predictors of clinical outcome in FMR on multivariate analysis. Conclusions The API method better predicts clinical events and outcome in FMR compared to established grading methods. Therefore, the API method may be considered for grading FMR severity in clinical practice.

Alternative reticles have the potential to improve EPE for low-k1 EUV lithography on multiple aspects, by reducing mask 3D effects and improving optical contrast. We study the application of high-k masks and attenuated phase-shift masks at diffraction level and show that mitigation of mask 3D effects, such as contrast fading, is crucial for both good performance of both alternative-reticle types. We present optimum embodiments for both mask types. We find that the optimum attenuated phase-shift mask (PSM) results in a phase shift of 1.2 π. The extra 0.2 π phase shift required for the EUV mask compared to its DUV counterpart is needed to compensate the strong mask 3D effects; the 1.2 π phase shift is crucial for good performance at small pitch and was found for all 3 materials studied in this work: Ru, Pd, and Mo. We show that our Rubased attenuated PSM embodiment results in a strong gain in normalized image log slope (NILS).

EUV lithography is being used at relatively high-k1 Rayleigh factors. Advancing EUV to smaller resolution requires several technological advancements. The EUV reticle is a strong contributor that limits current EUV imaging performance. Improvements with advanced mask types are required to reduce mask 3D effects and to improve image contrast. This will enable low-k1 resolution with reduced stochastic defect rates. In this paper we discuss what the requirements of high-k absorber masks and attenuated phase shift masks are to achieve optimal imaging performance. Recommendations on the mask stack composition and the application of mask types to different use cases are based on the physical understanding of the mask diffraction spectrum.

EUV lithography is entering High Volume Manufacturing at relative high Rayleigh factor k1 above 0.4. In comparison immersion lithography has been pushed to k1 values of 0.3 or below over the last two decades. One of the strong contributors determining the effective usable resolution is the mask absorber stack. The mask stack alters the diffraction by modifying the phase and intensity of the diffracted orders. In this paper we show the exposure results of a test mask having higher absorbance of EUV light and the advantages of reduced Mask 3D effects to imaging.

We present a case of a 71-year-old woman with recurrent stroke episodes due to non-bacterial thrombotic endocarditis (NBTE) leading to the diagnosis of an early-stage breast carcinoma. NBTE is associated with a variety of inflammatory states, including malignancy. NBTE presents itself with systemic embolization, mostly stroke. Treatment consists of treating the underlying condition and start of systemic anticoagulation therapy. Cardiac surgery is restricted to highly selected cases, since prognosis usually is limited by the neoplasm, which usually is in an advanced stage at time of diagnosis of NBTE. The malignancy usually is diagnosed prior to NBTE. Cases presenting with NBTE leading to the diagnosis of malignancy, however, are rarely reported. To our knowledge, we present the first case leading to the diagnosis of an early-stage breast carcinoma.

We present an integrated confocal Raman microscope in a focused ion beam scanning electron microscope (FIB SEM). The integrated system enables correlative Raman and electron microscopic analysis combined with focused ion beam sample modification on the same sample location. This provides new opportunities, for example the combination of nanometer resolution with Raman advances the analysis of sub-diffraction-sized particles. Further direct Raman analysis of FIB engineered samples enables in situ investigation of sample changes. The Raman microscope is an add-on module to the electron microscope. The optical objective is brought into the sample chamber, and the laser source, and spectrometer are placed in a module attached onto and outside the chamber. We demonstrate the integrated Raman FIB SEM function with several experiments. First, correlative Raman and electron microscopy is used for the investigation of (sub-)micrometer-sized crystals. Different crystals are identified with Raman, and in combination with SEM the spectral information is combined with structurally visible polymorphs and particle sizes. Analysis of sample changes made with the ion beam is performed on (1) structures milled in a silicon substrate and (2) after milling with the FIB on an organic polymer. Experiments demonstrate the new capabilities of an integrated correlative Raman–FIB–SEM