Bioenergetic consequences of repeated catch-and-release fisheries interactions on adult steelhead across a range of ecologically relevant water temperatures.

The biological consequences of catch-and-release angling have been studied for decades, yet little is known about the compounding effects of repeated recreational fisheries recaptures on the physiology and behaviour of angled fish. Using heart rate biologgers and behavioural assays, this study investigated the physiological and behavioural consequences of multiple simulated angling events (i.e., repeated stressors) on female steelhead (Oncorhynchus mykiss), under current (6 °C) and future (11 °C) water temperature scenarios. While steelhead in the warmer water temperature scenario demonstrated alterations in cardiac function (e.g., increases in maximum heart rate and scope of heart rate) and evidence of behavioural impairments (e.g., decreases in chase activity and landing time) over the course of two simulated angling events, cold water treated fish had negligible change. Fish subjected to two simulated angling events under warm water temperature conditions tended to demonstrate an increase in recovery time and scope for heart rate, and a decrease in resting heart rate. A second experiment was conducted to test for sex-specific differences in the heart rate response of steelhead subjected to an increase in water temperature. Females demonstrated a higher scope for heart rate when compared to males during the event and during recovery. More work is needed to better understand the interaction between multiple angling events and recovery from these events at various water temperatures, and the biological basis for sex-specific differences in cardiac function and response to challenges. This study contributes to a growing body of evidence on the effects of repeated stressors on wild fish.

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.

Layer-specific strain in patients with heart failure using cardiovascular magnetic resonance: not all layers are the same.

BACKGROUND: Global longitudinal strain (GLS), most commonly measured at the endocardium, has been shown to be superior to left ventricular (LV) ejection fraction (LVEF) for the identification of systolic dysfunction and prediction of outcomes in heart failure (HF). We hypothesized that strains measured at different myocardial layers (endocardium = ENDO, epicardium = EPI, average = AVE) will have distinct diagnostic and predictive performance for patients with HF. METHODS: Layer-specific GLS, layer-specific global circumferential strain (GCS) and global radial strain (GRS) were evaluated by cardiovascular magnetic resonance imaging (CMR) feature tracking in the Alberta HEART study. A total of 453 subjects consisted of healthy controls (controls, n = 77), at-risk for HF (at-risk, n = 143), HF with preserved ejection fraction (HFpEF, n = 87), HF with mid-range ejection fraction (HFmrEF, n = 88) and HF with reduced ejection fraction (HFrEF, n = 58). For outcomes analysis, CMR-derived imaging parameters were adjusted with a base model that included age and N-terminal prohormone of b-type natriuretic peptide (NT-proBNP) to test their independent association with 5-year all-cause mortality. RESULTS: GLS_EPI distinguished all groups with preserved LVEF (controls - 16.5 ± 2.4% vs. at-risk - 15.5 ± 2.7% vs. HFpEF - 14.1 ± 3.0%, p < 0.001) while GLS_ENDO and all GCS (all layers) were similar among these groups. GRS was reduced in HFpEF (41.1 ± 13.8% versus 48.9 ± 10.7% in controls, p < 0.001) and the difference between GLS_EPI and GLS_ENDO were significantly larger in HFpEF as compared to controls. Within the preserved LVEF groups, reduced GRS and GLS_EPI were significantly associated with increased LV mass (LVM) and LVM/LV end-diastolic volume EDV (concentricity). In multivariable analysis, only GLS_AVE and GRS predicted 5-year all-cause mortality (all ps < 0.05), with the strongest association with 5-year all-cause mortality by Akaike Information Criterion analysis and significant incremental value for outcomes prediction beyond LVEF or GLS_ENDO by the likelihood ratio test. CONCLUSION: Global strains measured on endocardium, epicardium or averaged across the wall thickness are not equivalent for the identification of systolic dysfunction or outcomes prediction in HF. The endocardium-specific strains were shown to have poorest all-around performance. GLS_AVE and GRS were the only CMR parameters to be significantly associated with 5-year all-cause mortality in multivariable analysis. GLS_EPI and GRS, as well as the difference in endocardial and epicardial strains, were sensitive to systolic dysfunction among HF patients with normal LVEF (> 55%), in whom lower strains were associated with increased concentricity.

Effects of age, gender, and risk-factors for heart failure on native myocardial T1 and extracellular volume fraction using the SASHA sequence at 1.5T.

BACKGROUND: Understanding cardiac MR T1 mapping values might require examination of the effects of age, gender, and heart failure risk factors. PURPOSE/HYPOTHESIS: To evaluate the effects of gender, age, and presence of heart failure risk factors on myocardial native T1 and extracellular volume fraction (ECV). STUDY TYPE: Retrospective, cross-sectional, observational study. POPULATION: Secondary analysis of cardiac MR data, separated by gender and health status, based on the presence of at least one heart failure risk factor. FIELD STRENGTH/SEQUENCE: Cardiac MR imaging at 1.5T, including T1 mapping using the SAturation recovery single-SHot Acquisition (SASHA) sequence. ASSESSMENT: Interventricular septal region-of-interest analysis for assessment of native T1 and ECV. STATISTICAL TESTS: Group comparisons performed using Student t-test, or nonparametric equivalent. Linear regression was used to assess relationships between age and T1 measurements. RESULTS: Native T1 and ECV were available in 187 and 143 subjects, respectively. T1 and ECV were independent of age in all groups (Native T1 : healthy women P = 0.655; healthy men P = 0.906; at-risk women P = 0.487; at-risk men P = 0.683; ECV: healthy women P = 0.685; healthy men P = 0.199; at-risk women P = 0.152; at-risk men P = 0.747). T1 and ECV were higher in healthy women versus men (1202 ± 30 ms versus 1167 ± 36 ms, P = 0.0000 and 22 ± 2% versus 20 ± 2%, P = 0.0089), while values were similar in women and men with risk factors (1197 ± 55 ms versus 1193 ± 45 ms, P = 0.6556, 21 ± 2% versus 21 ± 3%, P = 0.5039). No differences existed in native T1 or ECV between women with or without risk factors (P = 0.6344 and P = 0.1026), whereas men with risk factors showed higher native T1 values (P = 0.0070). DATA CONCLUSION: Native T1 and ECV measured with SASHA do not vary with age, regardless of gender or the presence of factors for heart failure. Native T1 and ECV are higher in healthy women than men, but do not differ in the presence of risk factors, suggesting a different myocardial response to risk factors between genders. LEVEL OF EVIDENCE: 3 Technical Efficacy: Stage 3 J. Magn. Reson. Imaging 2018;47:1307-1317.

Fragmented QRS complexes after acute myocardial infarction are independently associated with unfavorable left ventricular remodeling.

BACKGROUND: Recovery of left ventricular ejection fraction (LVEF) after acute myocardial infarction (MI) is not universal and is difficult to predict. Fragmented QRS (fQRS) complexes are thought to be markers of myocardial scar. We hypothesized that fQRS complexes on 12­lead surface ECGs during the initial post-MI period would be associated with adverse LV remodeling over the following year. METHODS: Change in LVEF between the early (0-2 month) and later (2-12 month) post-MI periods was assessed in two independent cohorts of post-MI patients with initial LV dysfunction. A decline or no recovery in LVEF (ΔLVEF ≤0%) was used as a primary outcome. fQRS complexes were measured on 12­lead ECGs within a week of acute MI. A subset of patients underwent cardiac magnetic resonance imaging (CMR) for scar quantification. RESULTS: Of 705 patients in the combined cohort, 27% experienced the primary outcome (average ΔLVEF of -4%). fQRS complexes were associated with a two-fold higher risk of no LVEF recovery, independent of prior MI or CABG, baseline LVEF, MI location and QRS duration or axis. Of 113 patients undergoing CMR, fQRS was associated with increased peri-infarct zone late gadolinium enhancement (13 ±â€¯5% vs 11 ±â€¯4%, p = 0.02), but not core infarct. CONCLUSIONS: Despite contemporary post-MI therapy, >1 in 4 patients will show a decline in LVEF during follow-up. Fragmented QRS complexes on 12­lead surface ECG early post-MI may be a valuable marker of unfavorable LV remodeling and correlate to increased peri-infarct scar on CMR imaging.

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.

Atrial shunts: presentation, investigation, and management, including recent advances in magnetic resonance imaging.

Atrial shunts are a common finding in both paediatric and adult populations. Recent developments in advanced imaging have widened the options for diagnosis and evaluation of such shunts. This paper reviews the various types of interatrial communications, discusses the features of clinical presentation in adults and children, and provides an overview of the clinical assessment including physical examination, electrocardiography, echocardiography, cardiac catheterisation, computed tomography, and magnetic resonance imaging. Focus will be placed on recent developments in magnetic resonance imaging that may improve the non-invasive evaluation of atrial shunts.

Enabling Reliable Visual Detection of Chronic Myocardial Infarction with Native T1 Cardiac MRI Using Data-Driven Native Contrast Mapping.

Purpose To investigate whether infarct-to-remote myocardial contrast can be optimized by replacing generic fitting algorithms used to obtain native T1 maps with a data-driven machine learning pixel-wise approach in chronic reperfused infarct in a canine model. Materials and Methods A controlled large animal model (24 canines, equal male and female animals) of chronic myocardial infarction with histologic evidence of heterogeneous infarct tissue composition was studied. Unsupervised clustering techniques using self-organizing maps and t-distributed stochastic neighbor embedding were used to analyze and visualize native T1-weighted pixel-intensity patterns. Deep neural network models were trained to map pixel-intensity patterns from native T1-weighted image series to corresponding pixels on late gadolinium enhancement (LGE) images, yielding visually enhanced noncontrast maps, a process referred to as data-driven native mapping (DNM). Pearson correlation coefficients and Bland-Altman analyses were used to compare findings from the DNM approach against standard T1 maps. Results Native T1-weighted images exhibited distinct pixel-intensity patterns between infarcted and remote territories. Granular pattern visualization revealed higher infarct-to-remote cluster separability with LGE labeling as compared with native T1 maps. Apparent contrast-to-noise ratio from DNM (mean, 15.01 ± 2.88 [SD]) was significantly different from native T1 maps (5.64 ± 1.58; P < .001) but similar to LGE contrast-to-noise ratio (15.51 ± 2.43; P = .40). Infarcted areas based on LGE were more strongly correlated with DNM compared with native T1 maps (R2 = 0.71 for native T1 maps vs LGE; R2 = 0.85 for DNM vs LGE; P < .001). Conclusion Native T1-weighted pixels carry information that can be extracted with the proposed DNM approach to maximize image contrast between infarct and remote territories for enhanced visualization of chronic infarct territories. Keywords: Chronic Myocardial Infarction, Cardiac MRI, Data-Driven Native Contrast Mapping Supplemental material is available for this article. © RSNA, 2024.

The Canadian Cardiovascular Society Classification of Acute Atherothrombotic Myocardial Infarction Based on Stages of Tissue Injury Severity: An Expert Consensus Statement.

Myocardial infarction (MI) remains a leading cause of morbidity and mortality. In atherothrombotic MI (ST-elevation MI and type 1 non-ST-elevation MI), coronary artery occlusion leads to ischemia. Subsequent cardiomyocyte necrosis evolves over time as a wavefront within the territory at risk. The spectrum of ischemia and reperfusion injury is wide: it can be minimal in aborted MI or myocardial necrosis can be large and complicated by microvascular obstruction and reperfusion hemorrhage. Established risk scores and infarct classifications help with patient management but do not consider tissue injury characteristics. This document outlines the Canadian Cardiovascular Society classification of acute MI. It is an expert consensus formed on the basis of decades of data on atherothrombotic MI with reperfusion therapy. Four stages of progressively worsening myocardial tissue injury are identified: (1) aborted MI (no/minimal myocardial necrosis); (2) MI with significant cardiomyocyte necrosis, but without microvascular injury; (3) cardiomyocyte necrosis and microvascular dysfunction leading to microvascular obstruction (ie, "no-reflow"); and (4) cardiomyocyte and microvascular necrosis leading to reperfusion hemorrhage. Each stage reflects progression of tissue pathology of myocardial ischemia and reperfusion injury from the previous stage. Clinical studies have shown worse remodeling and increase in adverse clinical outcomes with progressive injury. Notably, microvascular injury is of particular importance, with the most severe form (hemorrhagic MI) leading to infarct expansion and risk of mechanical complications. This classification has the potential to stratify risk in MI patients and lay the groundwork for development of new, injury stage-specific and tissue pathology-based therapies for MI.

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.

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.

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.

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.

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.

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.