Parameter subset reduction for imaging-based digital twin generation of patients with left ventricular mechanical discoordination.

BACKGROUND: Integration of a patient's non-invasive imaging data in a digital twin (DT) of the heart can provide valuable insight into the myocardial disease substrates underlying left ventricular (LV) mechanical discoordination. However, when generating a DT, model parameters should be identifiable to obtain robust parameter estimations. In this study, we used the CircAdapt model of the human heart and circulation to find a subset of parameters which were identifiable from LV cavity volume and regional strain measurements of patients with different substrates of left bundle branch block (LBBB) and myocardial infarction (MI). To this end, we included seven patients with heart failure with reduced ejection fraction (HFrEF) and LBBB (study ID: 2018-0863, registration date: 2019-10-07), of which four were non-ischemic (LBBB-only) and three had previous MI (LBBB-MI), and six narrow QRS patients with MI (MI-only) (study ID: NL45241.041.13, registration date: 2013-11-12). Morris screening method (MSM) was applied first to find parameters which were important for LV volume, regional strain, and strain rate indices. Second, this parameter subset was iteratively reduced based on parameter identifiability and reproducibility. Parameter identifiability was based on the diaphony calculated from quasi-Monte Carlo simulations and reproducibility was based on the intraclass correlation coefficient ( ICC ) obtained from repeated parameter estimation using dynamic multi-swarm particle swarm optimization. Goodness-of-fit was defined as the mean squared error ( χ 2 ) of LV myocardial strain, strain rate, and cavity volume. RESULTS: A subset of 270 parameters remained after MSM which produced high-quality DTs of all patients ( χ 2 < 1.6), but minimum parameter reproducibility was poor ( ICC min = 0.01). Iterative reduction yielded a reproducible ( ICC min = 0.83) subset of 75 parameters, including cardiac output, global LV activation duration, regional mechanical activation delay, and regional LV myocardial constitutive properties. This reduced subset produced patient-resembling DTs ( χ 2 < 2.2), while septal-to-lateral wall workload imbalance was higher for the LBBB-only DTs than for the MI-only DTs (p < 0.05). CONCLUSIONS: By applying sensitivity and identifiability analysis, we successfully determined a parameter subset of the CircAdapt model which can be used to generate imaging-based DTs of patients with LV mechanical discoordination. Parameters were reproducibly estimated using particle swarm optimization, and derived LV myocardial work distribution was representative for the patient's underlying disease substrate. This DT technology enables patient-specific substrate characterization and can potentially be used to support clinical decision making.

Multi-modal characterization of the left atrium by a fully automated integration of pre-procedural cardiac imaging and electro-anatomical mapping.

Background: The combination of information obtained from pre-procedural cardiac imaging and electro-anatomical mapping (EAM) can potentially help to locate new ablation targets. In this study we developed and evaluated a fully automated technique to align left atrial (LA) anatomies obtained from CT- and MRI-scans with LA anatomies obtained from EAM. Methods: Twenty-one patients scheduled for a pulmonary vein (PV) isolation with a pre-procedural MRI were enrolled. Additionally, a recent computed tomography (CT) scan was available in 12 patients. LA anatomies were segmented from MRI-scans using ADAS-AF (Galgo Medical, Barcelona) and from the CT-scans using Slicer3D. MRI and CT anatomies were aligned with the EAM anatomy using an iterative closest plane-to-plane algorithm. Initially, the algorithm included the PVs, LA appendage and mitral valve anulus as they are the most distinctive landmarks. Subsequently, the algorithm was applied again, excluding these structures, with only three iterative steps to refine the alignment of the true LA surface. The result of the alignments was quantified by the Euclidian distance between the aligned anatomies after excluding PVs, LA appendage and mitral anulus. Results: Our algorithm successfully aligned 20/21 MRI anatomies and 11/12 CT anatomies with the corresponding EAM anatomies. The average median residual distances were 1.9 ± 0.6 mm and 2.5 ± 0.8 mm for MRI and CT anatomies respectively. The average LA surface with a residual distance less than 5.00 mm was 89 ± 9% and 89 ± 10% for MRI and CT anatomies respectively. Conclusion: An iterative closest plane-to-plane algorithm is a reliable method to automatically align pre-procedural cardiac images with anatomies acquired during ablation procedures.

Myocardial Scar Detection Using High-Resolution Free-Breathing 3D Dark-Blood and Standard Breath-Holding 2D Bright-Blood Late Gadolinium Enhancement MRI: A Comparison of Observer Confidence.

OBJECTIVE: To compare observer confidence for myocardial scar detection using 3 different late gadolinium enhancement (LGE) data sets by 2 observers with different levels of experience. MATERIALS AND METHODS: Forty-one consecutive patients, who were referred for 3D dark-blood LGE MRI before implantable cardioverter-defibrillator implantation or ablation therapy and who underwent 2D bright-blood LGE MRI within a time frame of 3 months, were prospectively included. From all 3D dark-blood LGE data sets, a stack of 2D short-axis slices was reconstructed. All acquired LGE data sets were anonymized and randomized and evaluated by 2 independent observers with different levels of experience in cardiovascular imaging (beginner and expert). Confidence in detection of ischemic scar, nonischemic scar, papillary muscle scar, and right ventricular scar for each LGE data set was scored using a using a 3-point Likert scale (1 = low, 2 = medium, or 3 = high). Observer confidence scores were compared using the Friedman omnibus test and Wilcoxon signed-rank post hoc test. RESULTS: For the beginner observer, a significant difference in confidence regarding ischemic scar detection was observed in favor of reconstructed 2D dark-blood LGE compared with standard 2D bright-blood LGE (p = 0.030) while for the expert observer, no significant difference was found (p = 0.166). Similarly, for right ventricular scar detection, a significant difference in confidence was observed in favor of reconstructed 2D dark-blood LGE compared with standard 2D bright-blood LGE (p = 0.006) while for the expert observer, no significant difference was found (p = 0.662). Although not significantly different for other areas of interest, 3D dark-blood LGE and its derived 2D dark-blood LGE data set showed a tendency to score higher for all areas of interest at both experience levels. CONCLUSIONS: The combination of dark-blood LGE contrast and high isotropic voxels may contribute to increased observer confidence in myocardial scar detection, independent of observer's experience level but in particular for beginner observers.

Histopathological validation of semi-automated myocardial scar quantification techniques for dark-blood late gadolinium enhancement magnetic resonance imaging.

AIMS: To evaluate the performance of various semi-automated techniques for quantification of myocardial infarct size on both conventional bright-blood and novel dark-blood late gadolinium enhancement (LGE) images using histopathology as reference standard. METHODS AND RESULTS: In 13 Yorkshire pigs, reperfused myocardial infarction was experimentally induced. At 7 weeks post-infarction, both bright-blood and dark-blood LGE imaging were performed on a 1.5 T magnetic resonance scanner. Following magnetic resonance imaging (MRI), the animals were sacrificed, and histopathology was obtained. The percentage of infarcted myocardium was assessed per slice using various semi-automated scar quantification techniques, including the signal threshold vs. reference mean (STRM, using 3 to 8 SDs as threshold) and full-width at half-maximum (FWHM) methods, as well as manual contouring, for both LGE methods. Infarct size obtained by histopathology was used as reference. In total, 24 paired LGE MRI slices and histopathology samples were available for analysis. For both bright-blood and dark-blood LGE, the STRM method with a threshold of 5 SDs led to the best agreement to histopathology without significant bias (-0.23%, 95% CI [-2.99, 2.52%], P = 0.862 and -0.20%, 95% CI [-2.12, 1.72%], P = 0.831, respectively). Manual contouring significantly underestimated infarct size on bright-blood LGE (-1.57%, 95% CI [-2.96, -0.18%], P = 0.029), while manual contouring on dark-blood LGE outperformed semi-automated quantification and demonstrated the most accurate quantification in this study (-0.03%, 95% CI [-0.22, 0.16%], P = 0.760). CONCLUSION: The signal threshold vs. reference mean method with a threshold of 5 SDs demonstrated the most accurate semi-automated quantification of infarcted myocardium, without significant bias compared to histopathology, for both conventional bright-blood and novel dark-blood LGE.

Correlation between Cardiac MRI and Voltage Mapping in Evaluating Atrial Fibrosis: A Systematic Review.

Purpose: To provide an overview of existing literature on the association between late gadolinium enhancement (LGE) cardiac MRI and low voltage areas (LVA) obtained with electroanatomic mapping (EAM) or histopathology when assessing atrial fibrosis. Materials and Methods: A systematic literature search was conducted in the PubMed, Embase, and Cochrane Library databases to identify all studies published until June 7, 2022, comparing LGE cardiac MRI to LVA EAM and/or histopathology for evaluation of atrial fibrosis. The study protocol was registered at PROSPERO (registration no. CRD42022338243). Two reviewers independently evaluated the studies for inclusion. Risk of bias and applicability for each included study were assessed using Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2) criteria. Data regarding demographics, electrophysiology, LGE cardiac MRI, and study outcomes were extracted. Results: The search yielded 1048 total results, of which 22 studies were included. Nineteen of the 22 included studies reported a significant correlation between high signal intensity at LGE cardiac MRI and LVA EAM or histopathology. However, there was great heterogeneity between included studies regarding study design, patient samples, cardiac MRI performance and postprocessing, and EAM performance. Conclusion: Current literature suggests a correlation between LGE cardiac MRI and LVA EAM or histopathology when evaluating atrial fibrosis but high heterogeneity between studies, demonstrating the need for uniform choices regarding cardiac MRI and EAM acquisition in future studies.Keywords: Cardiac, MR Imaging, Left Atrium Supplemental material is available for this article. © RSNA, 2022.

New concepts in atrial fibrillation pathophysiology.

The current classification of atrial fibrillation (AF) is mainly focused on the clinical presentation according to the duration of AF episodes and the mode of termination, which incompletely reflect the severity and progressive nature of the underlying atrial disease. In this review article, "atrial cardiomyopathy" is discussed as a new concept in AF pathophysiology. Electrogram-, imaging-, and biomarker-derived measures and parameters to assess atrial cardiomyopathy, which will likely impact how AF is clinically classified and managed in the future, are presented.

Unilateral left-sided thoracoscopic ablation of atrial fibrillation concomitant to minimally invasive bypass grafting of the left anterior descending artery.

OBJECTIVES: Thoracoscopic ablation for atrial fibrillation (AF) and minimally invasive direct coronary artery bypass (MIDCAB) with robot-assisted left internal mammary artery (LIMA) harvesting may represent a safe and effective alternative to more invasive surgical approaches via sternotomy. The aim of our study was to describe the feasibility, safety and efficacy of a unilateral left-sided thoracoscopic AF ablation and concomitant MIDCAB surgery. METHODS: Retrospective analysis of a prospectively gathered cohort was performed of all consecutive patients with AF and at least a critical left anterior descending artery (LAD) stenosis that underwent unilateral left-sided thoracoscopic AF ablation and concomitant off-pump MIDCAB surgery in the Maastricht University Medical Centre between 2017 and 2021. RESULTS: Twenty-three patients were included [age 69 years (standard deviation = 8), paroxysmal AF 61%, left atrial volume index 42 ml/m2 (standard deviation = 11)]. Unilateral left-sided thoracoscopic isolation of the left (n = 23) and right (n = 22) pulmonary veins and box (n = 21) by radiofrequency ablation was succeeded by epicardial validation of exit- and entrance block (n = 22). All patients received robot-assisted LIMA harvesting and off-pump LIMA-LAD anastomosis through a left mini-thoracotomy. The perioperative complications consisted of one bleeding of the thoracotomy wound and one aborted myocardial infarction not requiring intervention. The mean duration of hospital stay was 6 days (standard deviation = 2). After discharge, cardiac hospital readmission occurred in 4 patients (AF n = 1; pleural- and pericardial effusion n = 2, myocardial infarction requiring the percutaneous intervention of the LIMA-LAD n = 1) within 1 year. After 12 months, 17/21 (81%) patients were in sinus rhythm when allowing anti-arrhythmic drugs. Finally, the left atrial ejection fraction improved postoperatively [26% (standard deviation = 11) to 38% (standard deviation = 7), P = 0.01]. CONCLUSIONS: In this initial feasibility and early safety study, unilateral left-sided thoracoscopic AF ablation and concomitant MIDCAB for LIMA-LAD grafting is a feasible, safe and efficacious for patients with AF and a critical LAD stenosis.

Rationale and Design of the ISOLATION Study: A Multicenter Prospective Cohort Study Identifying Predictors for Successful Atrial Fibrillation Ablation in an Integrated Clinical Care and Research Pathway.

Introduction: Continuous progress in atrial fibrillation (AF) ablation techniques has led to an increasing number of procedures with improved outcome. However, about 30-50% of patients still experience recurrences within 1 year after their ablation. Comprehensive translational research approaches integrated in clinical care pathways may improve our understanding of the complex pathophysiology of AF and improve patient selection for AF ablation. Objectives: Within the "IntenSive mOlecular and eLectropathological chAracterization of patienTs undergoIng atrial fibrillatiOn ablatioN" (ISOLATION) study, we aim to identify predictors of successful AF ablation in the following domains: (1) clinical factors, (2) AF patterns, (3) anatomical characteristics, (4) electrophysiological characteristics, (5) circulating biomarkers, and (6) genetic background. Herein, the design of the ISOLATION study and the integration of all study procedures into a standardized pathway for patients undergoing AF ablation are described. Methods: ISOLATION (NCT04342312) is a two-center prospective cohort study including 650 patients undergoing AF ablation. Clinical characteristics and routine clinical test results will be collected, as well as results from the following additional diagnostics: determination of body composition, pre-procedural rhythm monitoring, extended surface electrocardiogram, biomarker testing, genetic analysis, and questionnaires. A multimodality model including a combination of established predictors and novel techniques will be developed to predict ablation success. Discussion: In this study, several domains will be examined to identify predictors of successful AF ablation. The results may be used to improve patient selection for invasive AF management and to tailor treatment decisions to individual patients.

Baffle Complications in Adults After Atrial Switch for Transposition of the Great Arteries.

BACKGROUND: Baffle complications, ie, leakage or stenosis, after an atrial switch operation (AtrSO) for transposition of the great arteries (TGA) are difficult to detect with the use of routine transthoracic echocardiography (TTE). We examined baffle interventions and the prevalence of baffle complications. METHODS: This dual-centre study followed TGA-AtrSO patients for the occurrence of baffle interventions. In addition, in 2017-2019, prevalence of baffle complications was determined in patients undergoing routine contrast-enhanced (CE) TTE including various hemodynamic conditions and computed tomography (CT). Baffle leaks were defined as right-to-left shunting on CE-TTE and baffle stenosis as a systemic venous baffle diameter of < 10 mm on CT. RESULTS: In total, 67 TGA-AtrSO patients were followed to a median age of 38 (interquartile range 34-42) years, for a median of 9 (6-13) years. Baffle interventions were documented in 24 patients (36%). Cumulative risk of baffle interventions was 25% after 15 years of follow-up. Prevalence of baffle complications was determined in 29/67 patients. In total, 4 (14%) had patent baffles, 11 (38%) had leakage only, 5 (17%) had stenosis only, and 9 (31%) had both, while 24/29 (84%) were asymptomatic. Although baffle leaks were not associated with clinical characteristics, peak work rate during exercise TTE was lower in patients with vs without stenosis (89 ± 24 W vs 123 ± 21 W; P < 0.001). CONCLUSIONS: Baffle complications are common in TGA-AtrSO. The cumulative risk of baffle interventions was 25% after 15 years of follow-up. CE-TTE uncovered asymptomatic baffle leakage in the majority of patients, especially with examination during exercise. CT revealed baffle stenosis in almost half of the patients, which was associated with decreased exercise tolerance. Awareness of these findings may alter clinical follow-up.

A Boolean Dilemma: True or False Aneurysm?

A feared complication of acute myocardial infarction is the formation of a cardiac pseudoaneurysm. We report a case of a gargantuan, arrhythmogenic left-ventricular pseudoaneurysm with contradictory morphological characteristics. The integrative use of high-resolution 3-dimensional magnetic resonance imaging and computed tomography proved essential for the diagnostic discrimination and successful therapeutic intervention. (Level of Difficulty: Advanced.).

Transforming a pre-existing MRI environment into an interventional cardiac MRI suite.

AIMS: To illustrate the practical and technical challenges along with the safety aspects when performing MRI-guided electrophysiological procedures in a pre-existing diagnostic magnetic resonance imaging (MRI) environment. METHODS AND RESULTS: A dedicated, well-trained multidisciplinary interventional cardiac MRI team (iCMR team), consisting of electrophysiologists, imaging cardiologists, radiologists, anaesthesiologists, MRI physicists, electrophysiological (EP) and MRI technicians, biomedical engineers, and medical instrumentation technologists is a prerequisite for a safe and feasible implementation of CMR-guided electrophysiological procedures (iCMR) in a pre-existing MRI environment. A formal dry run "mock-up" to address the entire spectrum of technical, logistic, and safety issues was performed before obtaining final approval of the Board of Directors. With this process we showed feasibility of our workflow, safety protocol, and bailout procedures during iCMR outside the conventional EP lab. The practical aspects of performing iCMR procedures in a pre-existing MRI environment were addressed and solidified. Finally, the influence on neighbouring MRI scanners was evaluated, showing no interference. CONCLUSION: Transforming a pre-existing diagnostic MRI environment into an iCMR suite is feasible and safe. However, performing iCMR procedures outside the conventional fluoroscopic lab, poses challenges with technical, practical, and safety aspects that need to be addressed by a dedicated multi-disciplinary iCMR team.

Cardiovascular magnetic resonance accurately detects obstructive coronary artery disease in suspected non-ST elevation myocardial infarction: a sub-analysis of the CARMENTA Trial.

BACKGROUND: Invasive coronary angiography (ICA) is still the reference test in suspected non-ST elevation myocardial infarction (NSTEMI), although a substantial number of patients do not have obstructive coronary artery disease (CAD). Early cardiovascular magnetic resonance (CMR) may be a useful gatekeeper for ICA in this setting. The main objective was to investigate the accuracy of CMR to detect obstructive CAD in NSTEMI. METHODS: This study is a sub-analysis of a randomized controlled trial investigating whether a non-invasive imaging-first strategy safely reduced the number of ICA compared to routine clinical care in suspected NSTEMI (acute chest pain, non-diagnostic electrocardiogram, high sensitivity troponin T > 14 ng/L), and included 51 patients who underwent CMR prior to ICA. A stepwise approach was used to assess the diagnostic accuracy of CMR to detect (1) obstructive CAD (diameter stenosis ≥ 70% by ICA) and (2) an adjudicated final diagnosis of acute coronary syndrome (ACS). First, in all patients the combination of cine, T2-weighted and late gadolinium enhancement (LGE) imaging was evaluated for the presence of abnormalities consistent with a coronary etiology in any sequence. Hereafter and only when the scan was normal or equivocal, adenosine stress-perfusion CMR was added. RESULTS: Of 51 patients included (63 ± 10 years, 51% male), 34 (67%) had obstructive CAD by ICA. The sensitivity, specificity and overall accuracy of the first step to diagnose obstructive CAD were 79%, 71% and 77%, respectively. Additional vasodilator stress-perfusion CMR was performed in 19 patients and combined with step one resulted in an overall sensitivity of 97%, specificity of 65% and accuracy of 86%. Of the remaining 17 patients with non-obstructive CAD, 4 (24%) had evidence for a myocardial infarction on LGE, explaining the modest specificity. The sensitivity, specificity and overall accuracy to diagnose ACS (n = 43) were 88%, 88% and 88%, respectively. CONCLUSION: CMR accurately detects obstructive CAD and ACS in suspected NSTEMI. Non-obstructive CAD is common with CMR still identifying an infarction in almost one-quarter of patients. CMR should be considered as an early diagnostic approach in suspected NSTEMI. TRIAL REGISTRATION: The CARMENTA trial has been registered at ClinicalTrials.gov with identifier NCT01559467.

Quantification of Mitral Valve Regurgitation from 4D Flow MRI Using Semiautomated Flow Tracking.

PURPOSE: To compare the accuracy of semiautomated flow tracking with that of semiautomated valve tracking in the quantification of mitral valve (MV) regurgitation from clinical four-dimensional (4D) flow MRI data obtained in patients with mild, moderate, or severe MV regurgitation. MATERIALS AND METHODS: The 4D flow MRI data were retrospectively collected from 30 patients (21 men; mean age, 61 years ± 10 [standard deviation]) who underwent 4D flow MRI from 2006 to 2016. Ten patients had mild MV regurgitation, nine had moderate MV regurgitation, and 11 had severe MV regurgitation, as diagnosed by using semiquantitative echocardiography. The regurgitant volume (Rvol) across the MV was obtained using three methods: indirect quantification of Rvol (RvolINDIRECT), semiautomated quantification of Rvol using valve tracking (RvolVALVE), and semiautomated quantification of Rvol using flow tracking (RvolFLOW). A second observer repeated the measurements. Aortic valve flow was quantified as well to test for intervalve consistency. The Wilcoxon signed rank test, orthogonal regression, Bland-Altman analysis, and coefficients of variation were used to assess agreement among measurements and between observers. RESULTS: RvolFLOW was higher (median, 24.8 mL; interquartile range [IQR], 14.3-45.7 mL) than RvolVALVE (median, 9.9 mL; IQR, 6.0-16.9 mL; P < .001). Both RvolFLOW and RvolVALVE differed significantly from RvolINDIRECT (median, 19.1 mL; IQR, 4.1-47.5 mL; P = .03). RvolFLOW agreed more with RvolINDIRECT (y = 0.78x + 12, r = 0.88) than with RvolVALVE (y = 0.16x + 8.1, r = 0.53). Bland-Altman analysis revealed underestimation of RvolVALVE in severe MV regurgitation. Interobserver agreement was excellent for RvolFLOW (r = 0.95, coefficient of variation = 27%) and moderate for RvolVALVE (r = 0.72, coefficient of variation = 57%). Orthogonal regression demonstrated better intervalve consistency for flow tracking (y = 1.2x - 13.4, r = 0.82) than for valve tracking (y = 2.7x - 92.4, r = 0.67). CONCLUSION: Flow tracking enables more accurate 4D flow MRI-derived MV regurgitation quantification than valve tracking in terms of agreement with indirect quantification and intervalve consistency, particularly in severe MV regurgitation.Supplemental material is available for this article.© RSNA, 2020.