Right ventricular ejection fraction derived from intraoperative three-dimensional transesophageal echocardiography versus cardiac magnetic resonance imaging.

PURPOSE: Right ventricle (RV) assessment is critical during cardiac surgery. Traditional assessment consists of visual estimation and measurement of validated parameters. Cardiac magnetic resonance imaging (cMRI) is the gold standard for RV analysis, and transthoracic three-dimensional (3D) echocardiography is validated against this. We aimed to show that intraoperative 3D transesophageal echocardiography (TEE) RV assessment is feasible and can produce results that correlate with cMRI. METHODS: We recruited cardiac surgery patients who underwent cMRI within the preceding twelve preoperative months. An anesthetic protocol was followed pre-sternotomy and a 3D RV data set was acquired. We used TOMTEC 4D RV-Function to derive RV end-diastolic volume (EDV), end-systolic volume (ESV), and ejection fraction (EF). We compared these data with the corresponding MRI values. RESULTS: Twenty-five patients were included. Transesophageal echocardiography EDV and ESV differed from MRI measurements with a mean bias of -53 mL (95% confidence interval [CI], -80 to 26) and -21 mL (95% CI, -34 to -9). Transesophageal echocardiography EF did not differ significantly, with a mean bias of -4% (95% CI, -8 to 1). Results were unchanged after excluding MRIs older than 180 days. Correlation coefficients for EDV, ESV, and EF were r = 0.85, 0.91, and 0.80, respectively. Interclass correlation coefficients for EDV, ESV, and EF were 0.86, 0.89, and 0.96, respectively. CONCLUSIONS: Intraoperative TEE RV, EDV, and ESV are underestimated relative to cMRI because of analysis, anesthetic, and ventilation factors. The EF showed a low mean difference, and all values showed strong correlation with MRI. Reproducibility and feasibility were excellent and increased use in clinical practice should be considered.

RéSUMé: OBJECTIF: L'évaluation du ventricule droit (VD) est essentielle pendant la chirurgie cardiaque. L'évaluation traditionnelle consiste en une estimation visuelle et une mesure de paramètres validés. L'imagerie par résonance magnétique cardiaque (IRMc) est l'étalon-or pour l'analyse du VD, et l'échocardiographie transthoracique tridimensionnelle (3D) est validée par rapport cette modalité. Notre objectif était de démontrer que l'évaluation peropératoire du VD par l'échocardiographie transœsophagienne (ETO) était faisable et pouvait générer des résultats en corrélation avec l'IRMc. MéTHODE: Nous avons recruté des patient·es de chirurgie cardiaque ayant bénéficié d'une IRMc au cours des douze mois préopératoires précédents. Un protocole anesthésique a été suivi avant la sternotomie et un ensemble de données 3D sur le VD a été acquis. Nous avons utilisé le système TOMTEC 4D RV-Function pour calculer le volume télédiastolique (VTD), le volume télésystolique (VTS) et la fraction d'éjection (FE). Nous avons comparé ces données avec les valeurs correspondantes obtenues à l'IRM. RéSULTATS: Vingt-cinq personnes ont été incluses. Les valeurs de VTD et VTS obtenues à l'échocardiographie transœsophagienne différaient des mesures obtenues par IRM avec un biais moyen de ­53 mL (intervalle de confiance [IC] à 95 %, ­80 à 26) et ­21 mL (IC 95 %, ­34 à ­9). La FE obtenue par échocardiographie transœsophagienne ne différait pas significativement, avec un biais moyen de ­4 % (IC 95 %, ­8 à 1). Les résultats étaient inchangés après l'exclusion des IRM réalisés plus de 180 jours auparavant. Les coefficients de corrélation pour le VTD, le VTS et la FE étaient r = 0,85, 0,91 et 0,80, respectivement. Les coefficients de corrélation interclasse pour le VTD, le VTS et la FE étaient de 0,86, 0,89 et 0,96, respectivement. CONCLUSION: L'ETO peropératoire sous-estime les mesures du VD, du VTD et du VTS par rapport à l'IRMc en raison de facteurs d'analyse, d'anesthésie et de ventilation. La FE a montré une faible différence moyenne, et toutes les valeurs ont montré une forte corrélation avec l'IRM. La reproductibilité et la faisabilité étaient excellentes et une utilisation accrue dans la pratique clinique devrait être envisagée.

Improved accuracy and precision with three-parameter simultaneous myocardial T1 and T2 mapping using multiparametric SASHA.

PURPOSE: To develop and validate a three-parameter model for improved precision multiparametric SAturation-recovery single-SHot Acquisition (mSASHA) cardiac T1 and T2 mapping with high accuracy in a single breath-hold. METHODS: The mSASHA acquisition consists of nine images of variable saturation recovery and T2 preparation in 11 heartbeats with T1 and T2 values calculated using a three-parameter model. It was validated in simulations and phantoms at 3 T with comparison to a four-parameter joint T1 -T2 technique. The mSASHA acquisition was compared with MOLLI, SASHA, and T2 -prepared balanced SSFP in 10 volunteers. RESULTS: The mSASHA technique had high accuracy in phantoms compared to spin echo, with -0.2 ± 0.3% T1 error and -2.4 ± 1.3% T2 error. The mSASHA coefficient of variation in phantoms for T1 was similar to MOLLI (0.7 ± 0.2% for both) and T2 -prepared balanced SSFP for T2 (1.3 ± 0.7% vs 1.4 ± 0.3%, adjusted p > .05 for both). In simulations, three-parameter mSASHA had higher precision than four-parameter joint T1 -T2 for both T1 and T2 (46% and 11% reductions in T1 and T2 interquartile range for native myocardium). In vivo myocardial mSASHA T1 was similar to SASHA (1523 ± 18 ms vs 1520 ± 18 ms) with similar coefficient of variation to both MOLLI and SASHA (3.3 ± 0.6% vs 3.1 ± 0.6% and 3.3 ± 0.5% respectively, adjusted p > .05 for all). Myocardial mSASHA T2 was 37.1 ± 1.1 ms with similar precision to T2 -prepared balanced SSFP (6.7 ± 1.7% vs 6.0 ± 1.6%, adjusted p > .05). CONCLUSION: Three-parameter mSASHA provides high-accuracy cardiac T1 and T2 quantification in a single breath-hold with similar precision to MOLLI and T2 -prepared balanced SSFP. Further study is required to both establish normative values and demonstrate clinical utility in patient populations.

Right ventricular insertion site fibrosis in a dilated cardiomyopathy referral population: phenotypic associations and value for the prediction of heart failure admission or death.

BACKGROUND: Dilated cardiomyopathy (DCM) is increasingly recognized as a heterogenous disease with distinct phenotypes on late gadolinium enhancement (LGE) cardiovascular magnetic resonance (CMR) imaging. While mid-wall striae (MWS) fibrosis is a widely recognized phenotypic risk marker, other fibrosis patterns are prevalent but poorly defined. Right ventricular (RV) insertion (RVI) site fibrosis is commonly seen, but without objective criteria has been considered a non-specific finding. In this study we developed objective criteria for RVI fibrosis and studied its clinical relevance in a large cohort of patients with DCM. METHODS: We prospectively enrolled 645 DCM patients referred for LGE-CMR. All underwent standardized imaging protocols and baseline health evaluations. LGE images were blindly scored using objective criteria, inclusive of RVI site and MWS fibrosis. Associations between LGE patterns and CMR-based markers of adverse chamber remodeling were evaluated. Independent associations of LGE fibrosis patterns with the primary composite clinical outcome of heart failure admission or death were determined by multivariable analysis. RESULTS: The mean age was 56 ± 14 (28% female) with a mean left ventricular (LV) ejection fraction (LVEF) of 37%. At a median of 1061 days, 129 patients (20%) experienced the primary outcome. Any abnormal LGE was present in 306 patients (47%), inclusive of 274 (42%) meeting criteria for RVI site fibrosis and 167 (26%) for MWS fibrosis. All with MWS fibrosis showed RVI site fibrosis. Solitary RVI site fibrosis was associated with higher bi-ventricular volumes [LV end-systolic volume index (78 ± 39 vs. 66 ± 33 ml/m2, p = 0.01), RV end-diastolic volume index (94 ± 28 vs. 84 ± 22 ml/m2 (p < 0.01), RV end-systolic volume index (56 ± 26 vs. 45 ± 17 ml/m2, p < 0.01)], lower bi-ventricular function [LVEF 35 ± 12 vs. 39 ± 10% (p < 0.01), RV ejection fraction (RVEF) 43 ± 12 vs. 48 ± 10% (p < 0.01)], and higher extracellular volume (ECV). Patient with solitary RVI site fibrosis experienced a non-significant 1.4-fold risk of the primary outcome, increasing to a significant 2.6-fold risk when accompanied by MWS fibrosis. CONCLUSIONS: RVI site fibrosis in the absence of MWS fibrosis is associated with bi-ventricular remodelling and intermediate risk of heart failure admission or death. Our study findings suggest RVI site fibrosis to be pre-requisite for the incremental development of MWS fibrosis, a more advanced phenotype associated with greater LV remodeling and risk of clinical events.

Left atrial vortex size and velocity distributions by 4D flow MRI in patients with paroxysmal atrial fibrillation: Associations with age and CHA2 DS2 -VASc risk score.

BACKGROUND: Characterization of left atrial (LA) hemodynamics in paroxysmal atrial fibrillation (PAF) may provide valuable insights for thromboembolic risk. PURPOSE: To evaluate LA vortex formation and velocity distributions by 4D flow MRI and identify associations with age, LA/LV (left ventricle) function, and established risk scores. STUDY TYPE: Prospective clinical. POPULATION: Patients with PAF (n = 45, 46 ± 14 years) and healthy controls (n = 15, 54 ± 9 years) were enrolled. MRI SEQUENCES: 3T standardized cardiac MRI protocol inclusive of 4D flow MRI. ASSESSMENT: Flow analysis planes were prescribed at each pulmonary vein. Velocity distribution analysis and vortex size quantification by the Lambda2 (λ2 ) method were performed in the LA. STATISTICS: Pearson or Spearman's correlation coefficients, r, were calculated to identify relationships between 4D flow-derived LA parameters and age, LA/LV function, and CHA2 DS2 -VASc stroke risk score. Univariate and multivariate determinants of stroke risk were assessed using linear regressions. To compare parameters within multiple groups, one-way analysis of variance or Kruskal-Wallis was used. RESULTS: LA vortice sizes were observed in all subjects using λ2 showing inverse correlations with peak pulmonary vein inflow velocities (P < 0.05), and positive correlations with LA volume (P < 0.05). Vortex size was elevated in PAF at all phases of the cardiac cycle, being most prominent at end early diastole (3.98 ± 1.84 cm3 vs. 6.93 ± 3.11 cm3 , P = 0.001). Velocity distribution analysis showed a greater incidence of flow stasis among patients with PAF (P < 0.05). In univariate regression, vortex size was associated with the CHA2 DS2 -VASc risk score at peak systole (0.457 ± 0.038, P ≤ 0.001). However, in multivariate regression age was the dominant determinant of stroke risk (0.348 ± 0.012, P = 0.006). DATA CONCLUSION: This study demonstrated that LA vortex size is increased among low-risk patients with PAF and is associated with the CHA2 DS2 -VASc risk score. Age remained the dominant determinant of stroke risk. LEVEL OF EVIDENCE: 2 Technical Efficacy: Stage 3 J. Magn. Reson. Imaging 2020;51:871-884.

Three-dimensional thoracic aorta principal strain analysis from routine ECG-gated computerized tomography: feasibility in patients undergoing transcatheter aortic valve replacement.

BACKGROUND: Functional impairment of the aorta is a recognized complication of aortic and aortic valve disease. Aortic strain measurement provides effective quantification of mechanical aortic function, and 3-dimenional (3D) approaches may be desirable for serial evaluation. Computerized tomographic angiography (CTA) is routinely performed for various clinical indications, and offers the unique potential to study 3D aortic deformation. We sought to investigate the feasibility of performing 3D aortic strain analysis in a candidate population of patients undergoing transcatheter aortic valve replacement (TAVR). METHODS: Twenty-one patients with severe aortic valve stenosis (AS) referred for TAVR underwent ECG-gated CTA and echocardiography. CTA images were analyzed using a 3D feature-tracking based technique to construct a dynamic aortic mesh model to perform peak principal strain amplitude (PPSA) analysis. Segmental strain values were correlated against clinical, hemodynamic and echocardiographic variables. Reproducibility analysis was performed. RESULTS: The mean patient age was 81±6 years. Mean left ventricular ejection fraction was 52±14%, aortic valve area (AVA) 0.6±0.3 cm2 and mean AS pressure gradient (MG) 44±11 mmHg. CTA-based 3D PPSA analysis was feasible in all subjects. Mean PPSA values for the global thoracic aorta, ascending aorta, aortic arch and descending aorta segments were 6.5±3.0, 10.2±6.0, 6.1±2.9 and 3.3±1.7%, respectively. 3D PSSA values demonstrated significantly more impairment with measures of worsening AS severity, including AVA and MG for the global thoracic aorta and ascending segment (p<0.001 for all). 3D PSSA was independently associated with AVA by multivariable modelling. Coefficients of variation for intra- and inter-observer variability were 5.8 and 7.2%, respectively. CONCLUSIONS: Three-dimensional aortic PPSA analysis is clinically feasible from routine ECG-gated CTA. Appropriate reductions in PSSA were identified with increasing AS hemodynamic severity. Expanded study of 3D aortic PSSA for patients with various forms of aortic disease is warranted.

Objective criteria for septal fibrosis in non-ischemic dilated cardiomyopathy: validation for the prediction of future cardiovascular events.

BACKGROUND: Expert subjective reporting of mid-wall septal fibrosis on late gadolinium enhancement (LGE) images has been shown to predict major cardiovascular outcomes in patients with non-ischemic dilated cardiomyopathy (NIDCM). This study aims to establish objective criteria for non-experts to report clinically relevant septal fibrosis and compare its performance by such readers versus experts for the prediction of cardiovascular events. METHODS: LGE cardiovascular magnetic resonance (CMR) was performed in 118 consecutive patients with NIDCM (mean age 57 ± 14, 42 % female) and the presence of septal fibrosis scored by expert readers. CMR-naive readers performed signal threshold-based LGE quantification by referencing mean values of remote tissue and applying these to a pre-defined anatomic region to measure septal fibrosis. All patients were followed for the primary composite outcome of cardiac mortality or appropriate implantable cardioverter-defibrillator (ICD) therapy. RESULTS: The mean LVEF was 32 ± 12 %. At a median follow-up of 1.9 years, 20 patients (17 %) experienced a primary composite outcome. Expert visual scoring identified 55 patients with septal fibrosis. Non-expert septal fibrosis quantification was highly reproducible and identified mean septal fibrosis burden for three measured thresholds as follows; 5SD: 2.9 ± 3.6 %, 3SD: 6.9 ± 6.3 %, and 2SD: 11.1 ± 7.5 % of the left ventricular (LV) mass, respectively. By ROC analysis, optimal thresholds for prediction of the primary outcome were; 5SD: 2.74 % (HR 8.7, p < 0.001), 3SD: 6.63 % (HR 5.7, p = 0.001) and 2SD: 10.15 % (HR 6.1, p = 0.001). By comparison, expert visual scoring provided a HR of 5.3 (p = 0.001). In adjusted analysis, objective quantification by a novice reader (>5SD threshold) was the strongest independent predictor of the primary outcome (HR 8.7) and provided improved risk reclassification beyond LVEF alone (NRI 0.54, 95 % CI 0.16-0.92, p = 0.005). CONCLUSIONS: Novice readers were able to achieve superior risk prediction for future cardiovascular events versus experts using objective criteria for septal fibrosis in patients with NIDCM. Patients with a septal fibrosis burden >2.74 % of the LV mass (>5SD threshold) were at a 9-fold higher risk of cardiac death or appropriate ICD therapy versus those not meeting this criteria. As such, this study validates reproducible criteria applicable to all levels of expertise to identify NIDCM patients at high risk of future cardiovascular events.

Accuracy and reproducibility of semi-automated late gadolinium enhancement quantification techniques in patients with hypertrophic cardiomyopathy.

BACKGROUND: The presence and extent of late gadolinium enhancement (LGE) has been associated with adverse events in patients with hypertrophic cardiomyopathy (HCM). Signal intensity (SI) threshold techniques are routinely employed for quantification; Full-Width at Half-Maximum (FWHM) techniques are suggested to provide greater reproducibility than Signal Threshold versus Reference Mean (STRM) techniques, however the accuracy of these approaches versus the manual assignment of optimal SI thresholds has not been studied. In this study, we compared all known semi-automated LGE quantification techniques for accuracy and reproducibility among patients with HCM. METHODS: Seventy-six HCM patients (51 male, age 54 ± 13 years) were studied. Total LGE volume was quantified using 7 semi-automated techniques and compared to expert manual adjustment of the SI threshold to achieve optimal segmentation. Techniques tested included STRM based thresholds of >2, 3, 4, 5 and 6 SD above mean SI of reference myocardium, the FWHM technique, and the Otsu-auto-threshold (OAT) technique. The SI threshold chosen by each technique was recorded for all slices. Bland-Altman analysis and intra-class correlation coefficients (ICC) were reported for each semi-automated technique versus expert, manually adjusted LGE segmentation. Intra- and inter-observer reproducibility assessments were also performed. RESULTS: Fifty-two of 76 (68%) patients showed LGE on a total of 202 slices. For accuracy, the STRM >3SD technique showed the greatest agreement with manual segmentation (ICC = 0.97, mean difference and 95% limits of agreement = 1.6 ± 10.7 g) while STRM >6SD, >5SD, 4SD and FWHM techniques systematically underestimated total LGE volume. Slice based analysis of selected SI thresholds similarly showed the STRM >3SD threshold to most closely approximate manually adjusted SI thresholds (ICC = 0.88). For reproducibility, the intra- and inter-observer reproducibility of the >3SD threshold demonstrated an acceptable mean difference and 95% limits of agreement of -0.5 ± 6.8 g and -0.9 ± 5.6 g, respectively. CONCLUSIONS: FWHM segmentation provides superior reproducibility, however systematically underestimates total LGE volume compared to manual segmentation in patients with HCM. The STRM >3SD technique provides the greatest accuracy while retaining acceptable reproducibility and may therefore be a preferred approach for LGE quantification in this population.

Sex-based differences in the phenotypic expression and prognosis of idiopathic non-ischaemic cardiomyopathy: a cardiovascular magnetic resonance study.

AIMS: We sought to characterize sex-related differences in cardiovascular magnetic resonance-based cardiovascular phenotypes and prognosis in patients with idiopathic non-ischaemic cardiomyopathy (NICM). METHODS AND RESULTS: Patients with NICM enrolled in the Cardiovascular Imaging Registry of Calgary (CIROC) between 2015 and 2021 were identified. Z-score values for chamber volumes and function were calculated as standard deviation from mean values of 157 sex-matched healthy volunteers, ensuring reported differences were independent of known sex-dependencies. Patients were followed for the composite outcome of all-cause mortality, heart failure admission, or ventricular arrhythmia. A total of 747 patients were studied, 531 (71%) males. By Z-score values, females showed significantly higher left ventricular (LV) ejection fraction (EF; median difference 1 SD) and right ventricular (RV) EF (difference 0.6 SD) with greater LV mass (difference 2.1 SD; P < 0.01 for all) vs. males despite similar chamber volumes. Females had a significantly lower prevalence of mid-wall striae (MWS) fibrosis (22% vs. 34%; P < 0.001). Over a median follow-up of 4.7 years, 173 patients (23%) developed the composite outcome, with equal distribution in males and females. LV EF and MWS were significant independent predictors of the outcome (respective HR [95% CI] 0.97 [0.95-0.99] and 1.6 [1.2-2.3]; P = 0.003 and 0.005). There was no association of sex with the outcome. CONCLUSION: In a large contemporary cohort, NICM was uniquely expressed in females vs. males. Despite similar chamber dilation, females demonstrated greater concentric remodelling, lower reductions in bi-ventricular function, and a lower burden of replacement fibrosis. Overall, their prognosis remained similar to male patients with NICM.

Normative healthy reference values for global and segmental 3D principal and geometry dependent strain from cine cardiac magnetic resonance imaging.

3-Dimensional (3D) myocardial deformation analysis (3D-MDA) enables novel descriptions of geometry-independent principal strain (PS). Applied to routine 2D cine cardiovascular magnetic resonance (CMR), this provides unique measures of myocardial biomechanics for disease diagnosis and prognostication. However, healthy reference values remain undefined. This study describes age- and sex-stratified reference values from CMR-based 3D-MDA, including 3D PS. One hundred healthy volunteers were prospectively recruited following institutional ethics approval and underwent CMR imaging. 3D-MDA was performed using validated software. Age- and sex-stratified global and segmental strain measures were derived for conventional geometry-dependent [circumferential (CS), longitudinal (LS), and radial (RS)] and geometry-independent [minimum (minPS) and maximum principal (maxPS)] directions of deformation. Layer-specific contraction angle interactions were determined using local minPS vectors. The average age was 43 ± 15 years and 55% were women. Strain measures were higher in women versus men. 3D PS-based assessment of maximum tissue shortening (minPS) and maximum tissue thickening (maxPS) were greater than corresponding geometry-dependent markers of LS and RS, consistent with improved representation of local tissue deformations. Global maxPS amplitude best discriminated both age and sex. Segmental analyses showed greater strain amplitudes in apical segments. Transmural PS contraction angles were higher in females and showed a heterogeneous distribution across segments. In this study we provided age and sex-based reference values for 3D strain from CMR imaging, demonstrating improved capacity for 3D PS to document maximal local tissue deformations and to discriminate age and sex phenotypes. Novel markers of layer-specific strain angles from 3D PS were also described.

Patients with non-ischemic cardiomyopathy and mid-wall striae have similar arrhythmic outcomes as ischemic cardiomyopathy.

PURPOSE: While implantable cardioverter-defibrillator (ICD) therapy provides clear benefit in patients with ischemic cardiomyopathy (ICM), this is less clear in patients with non-ischemic cardiomyopathy (NICM). Mid-wall striae (MWS) fibrosis is an established cardiovascular magnetic resonance (CMR) risk marker observed in patients with NICM. We evaluated whether patients with NICM and MWS have similar risk of arrhythmia-related cardiovascular events as patients with ICM. METHODS: We studied a cohort of patients undergoing CMR. The presence of MWS was adjudicated by experienced physicians. The primary outcome was a composite of implantable cardioverter-defibrillator (ICD) implant, hospitalization for ventricular tachycardia, resuscitated cardiac arrest, or sudden cardiac death. Propensity-matched analysis was performed to compare outcomes for patients NICM with MWS and ICM. RESULTS: A total of 1,732 patients were studied, 972 NICM (706 without MWS, 266 with MWS) and 760 ICM. NICM patients with MWS were more likely to experience the primary outcome versus those without MWS (unadjusted subdistribution hazard ratio (subHR) 2.26, 95% confidence interval [CI] 1.51-3.41) with no difference versus ICM patients (unadjusted subHR 1.32, 95% CI 0.93-1.86). Similar results were seen in a propensity-matched population (adjusted subHR 1.11, 95% CI 0.63-1.98, p = 0.711). CONCLUSION: Patients with NICM and MWS demonstrate significantly higher arrhythmic risk compared to NICM without MWS. After adjustment, the arrhythmia risk of patients with NICM and MWS was similar to patients with ICM. Accordingly, physicians could consider the presence of MWS when making clinical decisions regarding arrhythmia risk management in patients with NICM.

Gastroesophageal reflux therapy is associated with longer survival in patients with idiopathic pulmonary fibrosis.

RATIONALE: Gastroesophageal reflux (GER) is highly prevalent in patients with idiopathic pulmonary fibrosis (IPF). Chronic microaspiration secondary to GER may play a role in the pathogenesis and natural history of IPF. OBJECTIVES: To investigate the relationship between GER-related variables and survival time in patients with IPF. METHODS: Regression analysis was used to investigate the relationship between GER-related variables and survival time in a retrospectively identified cohort of patients with well-characterized IPF from two academic medical centers. MEASUREMENTS AND MAIN RESULTS: Two hundred four patients were identified for inclusion. GER-related variables were common in this cohort: reported symptoms of GER (34%), a history of GER disease (45%), reported use of GER medications (47%), and Nissen fundoplication (5%). These GER-related variables were significantly associated with longer survival time on unadjusted analysis. After adjustment, the use of GER medications was an independent predictor of longer survival time. In addition, the use of gastroesophageal reflux medications was associated with a lower radiologic fibrosis score. These findings were present regardless of center. CONCLUSIONS: The reported use of GER medications is associated with decreased radiologic fibrosis and is an independent predictor of longer survival time in patients with IPF. These findings further support the hypothesis that GER and chronic microaspiration may play important roles in the pathobiology of IPF.

Intra-cardiac pressure drop and flow distribution of bicuspid aortic valve disease in preserved ejection fraction.

Background: Bicuspid aortic valve (BAV) is more than a congenital defect since it is accompanied by several secondary complications that intensify induced impairments. Hence, BAV patients need lifelong evaluations to prevent severe clinical sequelae. We applied 4D-flow magnetic resonance imaging (MRI) for in detail visualization and quantification of in vivo blood flow to verify the reliability of the left ventricular (LV) flow components and pressure drops in the silent BAV subjects with mild regurgitation and preserved ejection fraction (pEF). Materials and methods: A total of 51 BAV patients with mild regurgitation and 24 healthy controls were recruited to undergo routine cardiac MRI followed by 4D-flow MRI using 3T MRI scanners. A dedicated 4D-flow module was utilized to pre-process and then analyze the LV flow components (direct flow, retained inflow, delayed ejection, and residual volume) and left-sided [left atrium (LA) and LV] local pressure drop. To elucidate significant diastolic dysfunction in our population, transmitral early and late diastolic 4D flow peak velocity (E-wave and A-wave, respectively), as well as E/A ratio variable, were acquired. Results: The significant means differences of each LV flow component (global measurement) were not observed between the two groups (p > 0.05). In terms of pressure analysis (local measurement), maximum and mean as well as pressure at E-wave and A-wave timepoints at the mitral valve (MV) plane were significantly different between BAV and control groups (p: 0.005, p: 0.02, and p: 0.04 and p: <0.001; respectively). Furthermore, maximum pressure and pressure difference at the A-wave timepoint at left ventricle mid and left ventricle apex planes were significant. Although we could not find any correlation between LV diastolic function and flow components, Low but statistically significant correlations were observed with local pressure at LA mid, MV and LV apex planes at E-wave timepoint (R: -0.324, p: 0.005, R: -0.327, p: 0.004, and R: -0.306, p: 0.008, respectively). Conclusion: In BAV patients with pEF, flow components analysis is not sensitive to differentiate BAV patients with mild regurgitation and healthy control because flow components and EF are global parameters. Inversely, pressure (local measurement) can be a more reliable biomarker to reveal the early stage of diastolic dysfunction.

Machine Learning Patient-Specific Prediction of Heart Failure Hospitalization Using Cardiac MRI-Based Phenotype and Electronic Health Information.

Background: Heart failure (HF) hospitalization is a dominant contributor of morbidity and healthcare expenditures in patients with systolic HF. Cardiovascular magnetic resonance (CMR) imaging is increasingly employed for the evaluation of HF given capacity to provide highly reproducible phenotypic markers of disease. The combined value of CMR phenotypic markers and patient health information to deliver predictions of future HF events has not been explored. We sought to develop and validate a novel risk model for the patient-specific prediction of time to HF hospitalization using routinely reported CMR variables, patient-reported health status, and electronic health information. Methods: Standardized data capture was performed for 1,775 consecutive patients with chronic systolic HF referred for CMR imaging. Patient demographics, symptoms, Health-related Quality of Life, pharmacy, and routinely reported CMR features were provided to both machine learning (ML) and competing risk Fine-Gray-based models (FGM) for the prediction of time to HF hospitalization. Results: The mean age was 59 years with a mean LVEF of 36 ± 11%. The population was evenly distributed between ischemic (52%) and idiopathic non-ischemic cardiomyopathy (48%). Over a median follow-up of 2.79 years (IQR: 1.59-4.04) 333 patients (19%) experienced HF related hospitalization. Both ML and competing risk FGM based models achieved robust performance for the prediction of time to HF hospitalization. Respective 90-day, 1 and 2-year AUC values were 0.87, 0.83, and 0.80 for the ML model, and 0.89, 0.84, and 0.80 for the competing risk FGM-based model in a holdout validation cohort. Patients classified as high-risk by the ML model experienced a 34-fold higher occurrence of HF hospitalization at 90 days vs. the low-risk group. Conclusion: In this study we demonstrated capacity for routinely reported CMR phenotypic markers and patient health information to be combined for the delivery of patient-specific predictions of time to HF hospitalization. This work supports an evolving migration toward multi-domain data collection for the delivery of personalized risk prediction at time of diagnostic imaging.

Influence of Sex-Based Differences in Cardiac Phenotype on Atrial Fibrillation Recurrence in Patients Undergoing Pulmonary Vein Isolation.

Background: Pulmonary vein isolation (PVI) is a commonly engaged therapy for symptomatic atrial fibrillation (AF). Prior studies have documented elevated AF recurrence rates among females vs. males. Sex-specific mechanisms underlying this phenomenon are poorly understood. This prospective cohort study aimed to evaluate the sex-based differences in cardiac phenotype and their influence on (AF) recurrence following first-time PVI. Methods: A total of 204 consecutive patients referred for first-time PVI and 101 healthy subjects were prospectively studied by cardiovascular magnetic resonance (CMR) imaging. Multi-chamber volumetric and functional measures were assessed by sex-corrected Z-score analyses vs. healthy subjects. Patients were followed for a median of 2.6 years for the primary outcome of clinical AF recurrence. Multivariable analyses adjusting for age and comorbidities were performed to identify independent predictors of AF recurrence. Results: AF recurrence following first PVI occurred in 41% of males and 59% of females (p = 0.03). Females were older with higher prevalence of hypertension and thyroid disorders. Z-score-based analyses revealed significantly reduced ventricular volumes, greater left atrial (LA) volumes, and reduced LA contractility in females vs. males. Multivariable analysis revealed each of LA minimum and pre-systolic volumes and booster EF Z-scores to be independently associated with AF recurrence, providing respective hazard ratios of 1.10, 1.19, and 0.89 (p = 0.001, 0.03, and 0.01). Conclusion: Among patients referred for first time PVI, females were older and demonstrated significantly poorer LA contractile health vs. males, the latter independently associated with AF recurrence. Assessment of LA contractile health may therefore be of value to identify female patients at elevated risk of AF recurrence. Factors influencing female patient referral for PVI at more advanced stages of atrial disease warrant focused investigation.

Mid-wall striae fibrosis predicts heart failure admission, composite heart failure events, and life-threatening arrhythmias in dilated cardiomyopathy.

Heart failure (HF) admission is a dominant contributor to morbidity and healthcare costs in dilated cardiomyopathy (DCM). Mid-wall striae (MWS) fibrosis by late gadolinium enhancement (LGE) imaging has been associated with elevated arrhythmia risk. However, its capacity to predict HF-specific outcomes is poorly defined. We investigated its role to predict HF admission and relevant secondary outcomes in a large cohort of DCM patients. 719 patients referred for LGE MRI assessment of DCM were enrolled and followed for clinical events. Standardized image analyses and interpretations were conducted inclusive of coding the presence and patterns of fibrosis observed by LGE imaging. The primary clinical outcome was hospital admission for decompensated HF. Secondary heart failure and arrhythmic composite endpoints were also studied. Median age was 57 (IQR 47-65) years and median LVEF 40% (IQR 29-47%). Any fibrosis was observed in 228 patients (32%) with MWS fibrosis pattern present in 178 (25%). At a median follow up of 1044 days, 104 (15%) patients experienced the primary outcome, and 127 (18%) the secondary outcome. MWS was associated with a 2.14-fold risk of the primary outcome, 2.15-fold risk of the secondary HF outcome, and 2.23-fold risk of the secondary arrhythmic outcome. Multivariable analysis adjusting for all relevant covariates, inclusive of LVEF, showed patients with MWS fibrosis to experience a 1.65-fold increased risk (95% CI 1.11-2.47) of HF admission and 1-year event rate of 12% versus 7% without this phenotypic marker. Similar findings were observed for the secondary outcomes. Patients with LVEF > 35% plus MWS fibrosis experienced similar event rates to those with LVEF ≤ 35%. MWS fibrosis is a powerful and independent predictor of clinical outcomes in patients with DCM, identifying patients with LVEF > 35% who experience similar event rates to those with LVEF below this conventionally employed high-risk phenotype threshold.

Natural History of Myocardial Injury After COVID-19 Vaccine-Associated Myocarditis.

BACKGROUND: Acute myocarditis is a rare complication of mRNA-based COVID-19 vaccination. Little is known about the natural history of this complication. METHODS: Baseline and convalescent (≥ 90 days) cardiac magnetic resonance (CMR) imaging assessments were performed in 20 consecutive patients meeting Updated Lake Louise Criteria for acute myocarditis within 10 days of mRNA-based vaccination. CMR-based changes in left ventricular volumes, mass, ejection fraction (LVEF), markers of tissue inflammation (native T1 and T2 mapping), and fibrosis (late gadolinium enhancement [LGE] and extracellular volume [ECV]) were assessed between baseline and convalescence. Cardiac symptoms and clinical outcomes were captured. RESULTS: Median age was 23.1 years (range 18-39 years), and 17 (85%) were male. Convalescent evaluations were performed at a median (IQR) 3.7 (3.3-6.2) months. The LVEF showed a mean 3% absolute improvement, accompanied by a 7% reduction in LV end-diastolic volume and 5% reduction in LV mass (all P < 0.015). Global LGE burden was reduced by 66% (P < 0.001). Absolute reductions in global T2, native T1, and ECV of 2.1 ms, 58 ms, and 2.9%, repectively, were documented (all P ≤ 0.001). Of 5 patients demonstrating LVEF ≤ 50% at baseline, all recovered to above this threshold in convalescence. A total of 18 (90%) patients showed persistence of abnormal LGE although mean fibrosis burden was < 5% of LV mass in 85% of cases. No patient experienced major clinical outcomes. CONCLUSIONS: COVID-19 mRNA vaccine-associated myocarditis showed rapid improvements in CMR-based markers of edema, contractile function, and global LGE burden beyond 3 months of recovery in this young patient cohort. However, regional fibrosis following edema resolution was commonly observed, justifying need for ongoing surveillance.

Machine learning prediction of atrial fibrillation in cardiovascular patients using cardiac magnetic resonance and electronic health information.

Background: Atrial fibrillation (AF) is a commonly encountered cardiac arrhythmia associated with morbidity and substantial healthcare costs. While patients with cardiovascular disease experience the greatest risk of new-onset AF, no risk model has been developed to predict AF occurrence in this population. We hypothesized that a patient-specific model could be delivered using cardiovascular magnetic resonance (CMR) disease phenotyping, contextual patient health information, and machine learning. Methods: Nine thousand four hundred forty-eight patients referred for CMR imaging were enrolled and followed over a 5-year period. Seven thousand, six hundred thirty-nine had no prior history of AF and were eligible to train and validate machine learning algorithms. Random survival forests (RSFs) were used to predict new-onset AF and compared to Cox proportional-hazard (CPH) models. The best performing features were identified from 115 variables sourced from three data domains: (i) CMR-based disease phenotype, (ii) patient health questionnaire, and (iii) electronic health records. We evaluated discriminative performance of optimized models using C-index and time-dependent AUC (tAUC). Results: A RSF-based model of 20 variables (CIROC-AF-20) delivered an overall C-index of 0.78 for the prediction of new-onset AF with respective tAUCs of 0.80, 0.79, and 0.78 at 1-, 2- and 3-years. This outperformed a novel CPH-based model and historic AF risk scores. At 1-year of follow-up, validation cohort patients classified as high-risk of future AF by CIROC-AF-20 went on to experience a 17.3% incidence of new-onset AF, being 24.7-fold higher risk than low risk patients. Conclusions: Using phenotypic data available at time of CMR imaging we developed and validated the first described risk model for the prediction of new-onset AF in patients with cardiovascular disease. Complementary value was provided by variables from patient-reported measures of health and the electronic health record, illustrating the value of multi-domain phenotypic data for the prediction of AF.

Bicuspid aortic valve disease is associated with abnormal wall shear stress, viscous energy loss, and pressure drop within the ascending thoracic aorta: A cross-sectional study.

ABSTRACT: Bicuspid aortic valve (BAV) disease has significant gaps in its clinical management practices. To highlight the potential utility of advanced hemodynamic biomarkers in strengthening BAV assessment, we used 4-dimentional flow magnetic resonance imaging to investigate altered hemodynamics in the ascending aorta (AAo).A total of 32 healthy controls and 53 age-matched BAV patients underwent cardiac magnetic resonance imaging at 3T, with cine imaging and 4D-flow. Analysis planes were placed along 3D-segmented aortas at the left ventricular outflow tract (LVOT), sinuses of Valsalva, mid-ascending aorta (MAA), and proximal to the first aortic branch. Locations were analyzed for aortic diameter (normalized to body surface area), pressure drop (PD), viscous energy loss (EL), and wall shear stress (WSS) sub-vectors (axial wall shear stress, circumferential wall shear stress [WSSC], magnitude wall shear stress). Student's t tests, or non-parametric equivalents, compared parameters between cohorts. Univariable and multivariable analyses explored the associations of AAo diameter with hemodynamics within the BAV cohort.Compared to control cohort, BAV patients showed significantly greater PD (MAA: 9.5 ±â€Š8.0 vs 2.8 ±â€Š2.4 mm Hg; P < .01), EL (from LVOT-AA1: 7.39 ±â€Š4.57 mW vs 2.90 ±â€Š1.07 mW; P < .01), and WSSC (MAA: 0.3 ±â€Š0.1 vs 0.2 ±â€Š0.06 Pa; P ≤ .01) throughout the AAo. Correlational analyses revealed an inverse association between AAo diameter and both magnitude wall shear stress and axial wall shear stress.BAV patients exhibited increased PD, EL, and WSSC in the AAo, and an inverse association between AAo diameter and WSS sub-vectors. This demonstrated the impact of PD, EL, and WSS in BAV disease and the importance of altered hemodynamics in aortic remodelling.

A Novel High-Resolution Surface Electrocardiographic Method to Identify and Characterize Myocardial Scar: A Proof-of-Concept Study.

BACKGROUND: The placement of the left ventricular (LV) lead in an area free of myocardial scar is an important determinant of cardiac resynchronization therapy response. We sought to develop and validate a simple, practical, and novel electrocardiographic (ECG)-based approach to intraoperatively identify the presence of LV scar. We hypothesized that there would be a reduction in the measured amplitude of the LV pacing stimulus on the skin surface using a high-resolution (HR) ECG when pacing from LV regions with scar compared with regions without scar. We term this the ECG Amplitude Signal Evaluation (EASE) method. METHODS: Consecutive patients with ischemic LV systolic dysfunction and standard criteria for de novo cardiac resynchronization therapy implantation were prospectively enrolled. All underwent a preimplant contrast-enhanced cardiac magnetic resonance study to assess for scar. The average amplitude of the LV pacing impulse was sampled on HR surface ECG intraprocedurally and then compared with the cardiac magnetic resonance results. RESULTS: A total of 38 LV pacing sites were assessed among 13 recipients. The median voltage measured on the surface HR ECG in regions with scar was reduced by 41% (interquartile range, 17% to 63%), whereas there was no measurable change in voltage (interquartile range, 0 to 0%) in regions without scar compared with the maximal amplitude (Wilcoxon P < 0.0001). CONCLUSION: The EASE method appears to be of potential value as a novel intraoperative tool to guide LV lead placement to regions free of scar. Future work is required to validate the utility of this method in a larger patient cohort.

CONTEXTE: La mise en place de la sonde ventriculaire gauche dans une zone exempte de cicatrice myocardique est un facteur déterminant de la réponse au traitement de resynchronisation cardiaque. Nous avons cherché à développer et à valider une approche électrocardiographique (ECG) simple, concrète et novatrice afin de repérer de manière peropératoire la présence de tissu cicatriciel au ventricule gauche (VG). Nous avons émis l'hypothèse qu'il y aurait une diminution de l'amplitude du rythme de stimulation du ventricule gauche mesurée à la surface de la peau à l'ECG haute résolution (HR) lors de la stimulation de régions du VG présentant du tissu cicatriciel comparativement aux régions exemptes de cicatrices. Il s'agit de ce que nous appelons la méthode EASE ( E CG A mplitude S ignal E valuation). MÉTHODOLOGIE: Des patients vus de manière consécutive qui présentaient une dysfonction systolique ischémique du VG et répondaient aux critères standard pour l'implantation de novo d'un dispositif de resynchronisation cardiaque ont été recrutés de manière prospective. Tous ont fait l'objet d'une résonance magnétique cardiaque améliorée par injection d'un produit de contraste avant l'implantation pour évaluer la présence de tissu cicatriciel. L'amplitude moyenne de l'impulsion de stimulation du VG a été échantillonnée sur l'ECG de surface HR réalisé pendant l'intervention, puis comparée aux résultats de la résonance magnétique cardiaque. RÉSULTATS: En tout, 38 points de stimulation du VG ont été évalués chez 13 receveurs. Le voltage médian mesuré sur l'ECG de surface HR dans les régions présentant du tissu cicatriciel était réduit de 41 % (intervalle interquartile : 17 % à 63 %), tandis qu'il n'y avait pas de changement mesurable du voltage (intervalle interquartile : 0 à 0 %) dans les régions exemptes de cicatrices par rapport à l'amplitude maximale (test de Wilcoxon, p < 0,0001). CONCLUSION: La méthode EASE semble avoir une utilité potentielle en tant que nouvel outil peropératoire pour guider la mise en place de la sonde ventriculaire gauche dans les régions exemptes de cicatrices. Il faudra réaliser d'autres travaux pour valider l'utilité de cette méthode dans une cohorte de patients plus importante.

Hemodynamic Assessment in Bicuspid Aortic Valve Disease and Aortic Dilation: New Insights From Voxel-By-Voxel Analysis of Reverse Flow, Stasis, and Energetics.

Objectives: Clinical management decisions surrounding ascending aorta (AAo) dilation in bicuspid aortic valve (BAV) disease benefit from personalized predictive tools. 4D-flow MRI may provide patient-specific markers reflective of BAV-associated aortopathy. This study aims to explore novel 4D-flow MRI parametric voxel-by-voxel forward flow, reverse flow, kinetic energy and stasis in BAV disease. We hypothesize that novel parametric voxel-by-voxel markers will be associated with aortic dilation and referral for surgery and can enhance our understanding of BAV hemodynamics beyond standard metrics. Methods: A total of 96 subjects (73 BAV patients, 23 healthy controls) underwent MRI scan. Healthy controls had no known cardiovascular disease. Patients were clinically referred for AAo dilation assessment. Indexed diameters were obtained by dividing the aortic diameter by the patient's body surface area. Patients were followed for the occurrence of aortic surgery. 4D-flow analysis was performed by a single observer in five regions: left ventricular outflow tract (LVOT), AAo, arch, proximal descending aorta (PDAo), and distal descending aorta (DDAo). In each region peak velocity, kinetic energy (KE), forward flow (FF), reverse flow (RF), and stasis were measured on a voxel-by-voxel basis. T-tests (or non-parametric equivalent) compared flow parameters between cohorts. Univariate and multivariate analyses explored associations between diameter and parametric voxel-by-voxel parameters. Results: Compared to controls, BAV patients showed reduced stasis (p < 0.01) and increased RF and FF (p < 0.01) throughout the aorta, and KE remained similar. In the AAo, indexed diameter correlated with age (R = 0.326, p = 0.01), FF (R = -0.648, p < 0.001), RF (R = -0.441, p < 0.001), and stasis (R = -0.288, p < 0.05). In multivariate analysis, FF showed a significant inverse association with AAo indexed diameter, independent of age. During a median 179 ± 180 days of follow-up, 23 patients (32%) required aortic surgery. Compared to patients not requiring surgery, they showed increased KE and peak velocity in the proximal aorta (p < 0.01), accompanied by increased RF and reduced stasis throughout the entire aorta (p < 0.01). Conclusion: Novel voxel-by-voxel reverse flow and stasis were altered in BAV patients and are associated with aortic dilation and surgical treatment.