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.

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.

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.

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.

Right Ventricular Ejection Fraction for the Prediction of Major Adverse Cardiovascular and Heart Failure-Related Events: A Cardiac MRI Based Study of 7131 Patients With Known or Suspected Cardiovascular Disease.

BACKGROUND: There is increasing evidence that right ventricular ejection fraction (RVEF) may provide incremental value to left ventricular (LV) ejection fraction for the prediction of major adverse cardiovascular events. To date, generalizable utility for RVEF quantification in patients with cardiovascular disease has not been established. Using a large prospective clinical outcomes registry, we investigated the prognostic value of RVEF for the prediction of major adverse cardiovascular events- and heart failure-related outcomes. METHODS: Seven thousand one hundred thirty-one consecutive patients with known or suspected cardiovascular disease undergoing cardiovascular magnetic resonance imaging were prospectively enrolled. Multichamber volumetric quantification was performed by standardized operational procedures. Patients were followed for the primary composite outcome of all-cause death, survived cardiac arrest, admission for heart failure, need for transplantation or LV assist device, acute coronary syndrome, need for revascularization, stroke, or transient ischemic attack. A secondary, heart failure focused outcome of heart failure admission, need for transplantation/LV assist device or death was also studied. RESULTS: Mean age was 54±15 years. The mean LV ejection fraction was 55±14% (range 6%-90%) with a mean RVEF of 54±10% (range 9%-87%). At a median follow-up of 908 days, 870 (12%) patients experienced the primary composite outcome and 524 (7%) the secondary outcome. Each 10% drop in RVEF was associated with a 1.3-fold increased risk of the primary outcome (P<0.001) and 1.5-fold increased risk of the secondary outcome (P<0.001). RVEF was an independent predictor following comprehensive covariate adjustment, inclusive of LV ejection fraction. Patients with an RVEF<40% experienced a 3.1-fold risk of the primary outcome (P<0.001) with a 1-year cumulative event rate of 22% versus 7% above this cutoff. CONCLUSIONS: RVEF is a powerful and independent predictor of major adverse cardiac events with broad generalizability across patients with known or suspected cardiovascular disease. These findings support migration towards biventricular phenotyping for the classification of risk in clinical practice. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT04367220.

Effect of Active Cancer on the Cardiac Phenotype: A Cardiac Magnetic Resonance Imaging-Based Study of Myocardial Tissue Health and Deformation in Patients With Chemotherapy-Naïve Cancer.

Background The overlap between cancer and cardiovascular care continues to expand, with intersections emerging before, during, and following cancer therapies. To date, emphasis has been placed on how cancer therapeutics influence downstream cardiac health. However, whether active malignancy itself influences chamber volumes, function, or overall myocardial tissue health remains uncertain. We sought to perform a comprehensive cardiovascular magnetic resonance-based evaluation of cardiac health in patients with chemotherapy-naïve cancer with comparison with a healthy volunteer population. Methods and Results Three-hundred and eighty-one patients with active breast cancer or lymphoma before cardiotoxic chemotherapy exposure were recruited in addition to 102 healthy volunteers. Both cohorts underwent standardized cardiovascular magnetic resonance imaging with quantification of chamber volumes, ejection fraction, and native myocardial T1. Left ventricular mechanics were incrementally assessed using three-dimensional myocardial deformation analysis, providing global longitudinal, circumferential, radial, and principal peak-systolic strain amplitude and systolic strain rate. The mean age of patients with cancer was 53.8±13.4 years; 79% being women. Despite similar left ventricular ejection fraction, patients with cancer showed smaller chambers, increased strain amplitude, and systolic strain rate in both conventional and principal directions, and elevated native T1 versus sex-matched healthy volunteers. Adjusting for age, sex, hypertension, and diabetes mellitus, the presence of cancer remained associated with these cardiovascular magnetic resonance parameters. Conclusions The presence of cancer is independently associated with alterations in cardiac chamber size, function, and objective markers of tissue health. Dedicated research is warranted to elucidate pathophysiologic mechanisms underlying these findings and to explore their relevance to the management of patients with cancer referred for cardiotoxic therapies.

2021 Update on Safety of Magnetic Resonance Imaging: Joint Statement From Canadian Cardiovascular Society/Canadian Society for Cardiovascular Magnetic Resonance/Canadian Heart Rhythm Society.

Magnetic resonance imaging (MRI) is often considered the gold-standard test for characterizing cardiac as well as noncardiac structure and function. However, many patients with cardiac implantable electronic devices (CIEDs) and/or severe renal dysfunction are unable to undergo this test because of safety concerns. In the past 10 years, newer-generation CIEDs and gadolinium-based contrast agents (GBCAs) as well as coordinated care between imaging and heart rhythm device teams have mitigated risk to patients and improved access to MRI at many hospitals. The purpose of this statement is to review published data on safety of MRI in patients with conditional and nonconditional CIEDs in addition to patient risks from older and newer GBCAs. This statement was developed through multidisciplinary collaboration of pan-Canadian experts after a relevant and independent literature search by the Canadian Agency for Drugs and Technologies in Health. All recommendations align with the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system. Key recommendations include: (1) the development of standardized protocols for patients with a CIED undergoing MRI; (2) patients with MRI nonconditional pacemakers and pacemaker dependency should be programmed to asynchronous mode and those with MRI nonconditional transvenous defibrillators should have tachycardia therapies turned off during the scan; and (3) macrocyclic or newer linear GBCAs should be used in preference to older GBCAs because of their better safety profile in patients at higher risk of nephrogenic systemic fibrosis.

Sex-specific relationships between patterns of ventricular remodelling and clinical outcomes.

AIMS: Left ventricular hypertrophy (LVH) is the most common form of myocardial remodelling and predicts adverse outcomes in patients with coronary artery disease (CAD). However, sex-specific prevalence and prognostic significance of LVH patterns are poorly understood. We investigated the sex-specific influence of LVH pattern on clinical outcomes in patients undergoing cardiovascular magnetic resonance (CMR) and coronary angiography following adjustment for co-morbidities including CAD burden. METHODS AND RESULTS: Patients undergoing CMR and coronary angiography between 2005 and 2013 were included. Volumetric measurements of left ventricular (LV) mass with classification of concentric vs. eccentric remodelling patterns were determined from CMR cine images. Multivariable Cox analysis was performed to assess independent associations with the primary outcome of all-cause mortality. In total, 3754 patients were studied (mean age 59.3 ± 13.1 years), including 1039 (27.7%) women. Women were more likely to have concentric remodelling (8.1% vs. 2.1%, P < 0.001), less likely to have eccentric hypertrophy (15.1% vs. 26.8%, P < 0.001) and had a similar prevalence of concentric hypertrophy (6.1 vs. 5.2%, P = 0.296) compared to men. At a median follow-up of 3.7 years, 315 (8.4%) patients died. Following adjustment including CAD burden, concentric hypertrophy was associated with increased all-cause mortality in women [adjusted hazard ratio (HR) 3.48, P < 0.001] and men (adjusted HR 2.57, P < 0.001). Eccentric hypertrophy was associated with all-cause mortality only in women (adjusted HR 1.78, P = 0.047). CONCLUSION: Patterns of LV remodelling differ by sex and LVH and provides prognostic information in both men and women. Our findings support the presence of sex-specific factors influencing LV remodelling.

Neural-Network-Based Diagnosis Using 3-Dimensional Myocardial Architecture and Deformation: Demonstration for the Differentiation of Hypertrophic Cardiomyopathy.

The diagnosis of cardiomyopathy states may benefit from machine-learning (ML) based approaches, particularly to distinguish those states with similar phenotypic characteristics. Three-dimensional myocardial deformation analysis (3D-MDA) has been validated to provide standardized descriptors of myocardial architecture and deformation, and may therefore offer appropriate features for the training of ML-based diagnostic tools. We aimed to assess the feasibility of automated disease diagnosis using a neural network trained using 3D-MDA to discriminate hypertrophic cardiomyopathy (HCM) from its mimic states: cardiac amyloidosis (CA), Anderson-Fabry disease (AFD), and hypertensive cardiomyopathy (HTNcm). 3D-MDA data from 163 patients (mean age 53.1 ± 14.8 years; 68 females) with left ventricular hypertrophy (LVH) of known etiology was provided. Source imaging data was from cardiac magnetic resonance (CMR). Clinical diagnoses were as follows: 85 HCM, 30 HTNcm, 30 AFD, and 18 CA. A fully-connected-layer feed-forward neural was trained to distinguish HCM vs. other mimic states. Diagnostic performance was compared to threshold-based assessments of volumetric and strain-based CMR markers, in addition to baseline clinical patient characteristics. Threshold-based measures provided modest performance, the greatest area under the curve (AUC) being 0.70. Global strain parameters exhibited reduced performance, with AUC under 0.64. A neural network trained exclusively from 3D-MDA data achieved an AUC of 0.94 (sensitivity 0.92, specificity 0.90) when performing the same task. This study demonstrates that ML-based diagnosis of cardiomyopathy states performed exclusively from 3D-MDA is feasible and can distinguish HCM from mimic disease states. These findings suggest strong potential for computer-assisted diagnosis in clinical practice.

Treatment Decisions in Geriatric Cardiac Lymphoma Facilitated by Serial Cardiac Magnetic Resonance Imaging and Positron Emission Tomography.

A tumour encasing the right coronary was identified on computed tomography pulmonary embolism protocol in an 81-year-old man. Concerns regarding tolerability of chemotherapy in an octogenarian were addressed using cardiac magnetic resonance imaging to monitor a trial of modified-chemotherapy for his primary cardiac B-cell lymphoma. Residual activity on positron emission tomography computed tomography mandated consolidation with radiotherapy to achieve a tumor-free return to health. Despite advanced age, successful therapy in this, the oldest case of primary cardiac lymphoma reported, was facilitated by monitoring treatment effectiveness with advanced cardiac imaging and the use of standardized frailty scores in communicating his appropriate level of robustness for tolerating chemotherapy.

Une tumeur enveloppant l'artère coronaire droite a été décelée lors du protocole de tomodensitométrie à la recherche d'une embolie pulmonaire chez un homme de 81 ans. Les préoccupations relatives à la tolérance à la chimiothérapie chez un octogénaire ont été prises en considération lors de l'imagerie cardiaque par résonance magnétique pour surveiller l'essai d'une chimiothérapie modifiée de son lymphome cardiaque primitif à cellules B. L'activité résiduelle à la tomographie par émission de positons associée à la tomodensitométrie a rendu nécessaire la consolidation par radiothérapie pour un retour à la santé sans tumeur. En dépit de son âge avancé, la réussite du traitement de cet homme, le cas signalé le plus ancien de lymphome cardiaque primitif, a été facilitée par la surveillance de l'efficacité du traitement par une technique avancée d'imagerie cardiaque et l'utilisation des scores de fragilité standardisés pour connaître son degré de robustesse approprié pour tolérer la chimiothérapie.

Left Atrial Function Using Cardiovascular Magnetic Resonance Imaging Independently Predicts Life-Threatening Arrhythmias in Patients Referred to Receive a Primary Prevention Implantable Cardioverter Defibrillator.

BACKGROUND: In this study we aimed to investigate left atrial (LA) function, measured from routine cine cardiovascular magnetic resonance imaging, to determine its value for the prediction of sudden cardiac death (SCD) or appropriate implantable cardioverter defibrillator (ICD) shock in patients who received primary prevention ICD implantation. METHODS: We studied 203 patients with ischemic or idiopathic nonischemic dilated cardiomyopathy who underwent cardiovascular magnetic resonance imaging before primary prevention ICD implantation. LA volumes were measured at end-diastole and end-systole from 4- and 2-chamber cine images, and LA emptying function (LAEF) calculated. Patients were followed for the primary composite end point of SCD or appropriate ICD shock. RESULTS: Mean age was 61 ± 12 years with a mean left ventricular ejection fraction of 24 ± 7%. The mean LAEF was 27 ± 15% (range, 0.9%-73%). At a median follow-up of 1639 days, 35 patients (17%) experienced the primary composite outcome. LAEF was strongly associated with the primary outcome (P = 0.001); patients with an LAEF ≤ 30% experienced a cumulative event rate of 26.1% vs 5.7% (hazard ratio, 5.5; P < 0.001) in patients above this cutoff. This finding was maintained in multivariable analysis (hazard ratio, 4.7; P = 0.002) and was consistently shown in the ischemic and nonischemic dilated cardiomyopathy subgroups. CONCLUSIONS: LAEF is a simple, powerful, and independent predictor of SCD in patients being referred for primary prevention ICD implantation.

Intra-thoracic adiposity is associated with impaired contractile function in patients with coronary artery disease: a cardiovascular magnetic resonance imaging study.

The influence of visceral adiposity on left ventricular remodeling following coronary artery disease (CAD)-related events has not been examined to date. Using magnetic resonance imaging (MRI) we explored intra-thoracic fat volume (ITFV) and strain-based markers of adverse remodeling in patients with CAD. Forty-seven patients with known CAD (25 with prior MI, 22 without prior MI) were studied. ITFV was quantified using previously validated imaging techniques. Myocardial strain was derived from cine MRI using a validated 3D feature-tracking (FT) software. Segmental LGE quantification was performed and was used to incrementally constrain strain analyses to non-infarcted (i.e. remote) segments. Remote myocardial strain was compared to the non-MI control cohort and was explored for associations with ITFV. Mean age was 57 ± 13 years with a mean BMI of 30.0 ± 6.2 kg/m2 (range 20.3-38.4 kg/m2). Patients with versus without prior MI had similar demographics and BMI (29.4 ± 4.4 vs. 30.4 ± 7.9 kg/m2, p = 0.62). Patients with prior MI had lower mean peak strain than non-MI patients (p = 0.02), consistent with remote tissue contractile dysfunction. Inverse associations were identified between ITFV and mean peak strain in both the MI group (circumferential: r = 0.43, p = 0.03; radial: - 0.41, p = 0.04; minimum principal: r = 0.41, p = 0.04; maximum principal: r = - 0.43, p = 0.03) and non-MI group (circumferential: r = 0.42, p = 0.05; minimum principal: r = 0.45, p = 0.03). In those with prior MI higher ITFV was associated with a greater reduction in remote tissue strain. ITFV is associated with contractile dysfunction in patients with CAD. This association is prominent in the post-MI setting suggesting relevant influence on remote tissue health following ischemic injury. Expanded study of intra-thoracic adiposity as a modulator of myocardial health in patients with CAD is warranted.

3-Dimensional regional and global strain abnormalities in hypertrophic cardiomyopathy.

Hypertrophic cardiomyopathy (HCM) is characterized by myocardial disarray, hypertrophy, and fibrosis. Reduced global longitudinal strain and presence of late gadolinium enhancement (LGE) by cardiac magnetic resonance imaging (CMR) have been associated with an adverse prognosis. This study evaluated 3D principal and conventional strain characteristics of non-enhanced myocardium in patients with HCM. 3D principal and conventional strain analysis was conducted in 51 HCM patients and 38 healthy controls. Principal strain was reduced within the non-enhanced myocardium of HCM as compared with controls (maximum principal: 51.5 ± 23.7 vs. 75.1 ± 21.4%, P < 0.0001; minimum principal: - 18.4 ± 4.0 vs. - 20.1 ± 2.9%, P < 0.05). Principal strain within the non-enhanced myocardium was incrementally reduced in HCM patients with extensive global LGE ( ≥ 15%) (maximum principal: 41.6 ± 17.5 vs. 56.9 ± 25.9%, P < 0.05; minimum principal: - 16.9 ± 3.9 vs. - 19.1 ± 4.0%, P = 0.1), as was longitudinal ( - 10.5 ± 2.6 vs. - 12.7 ± 2.6%, P < 0.05) and circumferential strain ( - 11.0 ± 2.7 vs. - 14.0 ± 2.9%, P < 0.01). Principal strain within non-enhanced myocardium was significantly correlated with indexed LV mass (P < 0.0001), maximum (P = 0.0008), and mean wall thickness (P < 0.0001), but not LGE (P = 0.0841). In adjusted analysis, all strain measures within non-enhanced myocardium were independently associated with indexed LV mass (maximum principal: P = 0.0003; minimum principal: P = 0.0039; longitudinal: P = 0.0015; circumferential: P = 0.0002; radial: P = 0.0023). 3D principal strain of non-enhanced myocardium was significantly reduced in HCM patients as compared with controls, and was incrementally reduced among patients with more extensive global LGE. Comprehensive strain assessment may be considered in routine CMR assessment of HCM patients.