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Background: Sodium-glucose cotransporter-2 (SGLT2) inhibitors have demonstrated reduction in heart failure outcomes in patients with type 2 diabetes mellitus, although the exact mechanism of benefit remains unclear. Alteration in left atrial (LA) function due to chronic pressure or volume overload is a hallmark of heart failure., Objective: To evaluate the effect of the SGLT2 inhibitor empagliflozin on LA volume and function., Methods: 90 patients with coronary artery disease and type 2 diabetes (T2DM) were randomized to empagliflozin (n = 44) or placebo (n = 46), and underwent cardiac magnetic resonance (CMR) imaging at baseline and after 6 months. The main outcome was change in LA volume; LA function, including active and passive components, was also measured by a blinded reader., Results: At baseline, there was no significant difference in LA volumes between the empagliflozin (indexed maximum LA volume 26.4 ± 8.4mL/m 2 , minimum LA volume 11.1 ± 5.7mL/m 2 ) and placebo (indexed maximum LA volume 28.7 ± 8.2mL/m 2 , minimum LA volume 12.6 ± 5.0mL/m 2 ) groups. After 6 months, changes in LA volumes did not differ with adjusted difference (empagliflozin minus placebo): 0.99 mL/m 2 (95% CI: -1.7 to 3.7 mL/m 2 ; p = 0.47) for indexed maximum LA volume, and 0.87 mL/m 2 (95% CI: -0.9 to 2.6 mL/m 2 ; p = 0.32) for indexed minimum LA volume. Changes in total LA emptying fraction were also similar, with between-group adjusted mean difference - 0.01 (95% CI: -0.05 to 0.03, p = 0.59)., Conclusion: SGLT2 inhibition with empagliflozin for 6 months did not have a significant impact on LA volume and function in patients with T2DM and coronary artery disease. (Effects of Empagliflozin on Cardiac Structure in Patients with Type 2 Diabetes [EMPA-HEART]; NCT02998970)., (© 2024. The Author(s).)

Background: Cardiac amyloidosis is increasingly recognized as a significant contributor to cardiovascular morbidity and mortality. With the emergence of novel therapies, there is a growing interest in prognostication of patients with cardiac amyloidosis using cardiac magnetic resonance imaging (CMR). In this systematic review and meta-analysis, we aimed to examine the prognostic significance of myocardial native T1 and T2, and extracellular volume (ECV)., Methods: Observational cohort studies or single arms of clinical trials were eligible. MEDLINE, EMBASE and CENTRAL were systematically searched from their respective dates of inception to January 2023. No exclusions were made based on date of publication, study outcomes, or study language. The study populations composed of adult patients (≥18 years old) with amyloid cardiomyopathy. All studies included the use of CMR with and without intravenous gadolinium contrast administration to assess myocardial native T1 mapping, T2 mapping, and ECV in association with the pre-specified primary outcome of all-cause mortality. Data were extracted from eligible primary studies by two independent reviewers and pooled via the inverse variance method using random effects models for meta-analysis., Results: A total of 3852 citations were reviewed. A final nine studies including a total of 955 patients (mean age 65 ± 10 years old, 32% female, mean left ventricular ejection fraction (LVEF) 59 ± 12% and 24% had NYHA class III or IV symptoms) with cardiac amyloidosis [light chain amyloidosis (AL) 50%, transthyretin amyloidosis (ATTR) 49%, other 1%] were eligible for inclusion and suitable for data extraction. All included studies were single centered (seven with 1.5 T MRI scanners, two with 3.0 T MRI scanners) and non-randomized in design, with follow-up spanning from 8 to 64 months (median follow-up = 25 months); 320 patients died during follow-up, rendering a weighted mortality rate of 33% across studies. Compared with patients with AL amyloid, patients with ATTR amyloid had significantly higher mean left ventricular mass index (LVMi) (102 ± 34 g/m 2 vs 127 ± 37 g/m 2 , p = 0.02). N-terminal pro-brain natriuretic peptide (NT-proBNP), troponin T levels, mean native T1 values, ECV and T2 values did not differ between patients with ATTR amyloid and AL amyloid (all p > 0.25). Overall, the hazard ratios for mortality were 1.33 (95% CI = [1.10, 1.60]; p = 0.003; I 2  = 29%) for every 60 ms higher T1 time, 1.16 (95% CI = [1.09, 1.23], p < 0.0001; I 2  = 76%) for every 3% higher ECV, and 5.23 (95% CI = [2.27, 12.02]; p < 0.0001; I 2  = 0%) for myocardial-to-skeletal T2 ratio below the mean (vs above the mean)., Conclusion: Higher native T1 time and ECV, and lower myocardial to skeletal T2 ratio, on CMR are associated with worse mortality in patients with cardiac amyloidosis. Therefore, tissue mapping using CMR may offer a useful non-invasive technique to monitor disease progression and determine prognosis in patients with cardiac amyloidosis., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

The p.Arg301Gln variant in the α -galactosidase A gene ( GLA ) has been poorly described in the literature. The few reports show controversial information, with both classical and nonclassical Anderson-Fabry Disease (AFD) presentation patterns. The aim of this study was to analyze the penetrance, clinical phenotype, and biochemical profile of an international cohort of patients carrying the p.Arg301Gln genetic variant in the GLA gene. This was an observational, international, and retrospective cohort case series study of patients carrying the p.Arg301Gln variant in the GLA gene associated with AFD disease. Forty-nine p.Arg301Gln GLA carriers, 41% male, were analyzed. The penetrance was 63% in the entire cohort and 1.5 times higher in men. The mean age of symptoms onset was 41 years; compared to women, men presented symptoms earlier and with a shorter delay to diagnosis. The typical clinical triad-cornea verticillate, neuropathic pain, and angiokeratomas-affected only 20% of the cohort, with no differences between genders. During follow-up, almost 20% of the patients presented some type of nonfatal cardiovascular and renal event (stroke, need for dialysis, heart failure, and arrhythmias requiring intracardiac devices), predominantly affecting men. Residual levels were the most common finding of α-GAL A enzyme activity, only a few women had a normal level; a small proportion of men had undetectable levels. The incidence of combined outcomes including all causes of death was 33%, and the cumulative incidence of all-cause mortality was 9% at the follow-up. Patients carrying the p.Arg301Gln GLA variant have a high penetrance, with predominantly cardiorenal involvement and clinical onset of the disease in middle age. Only a small proportion showed the classic clinical presentation of AFD. As in other X-linked diseases, males were more affected by severe cardiovascular and renal events. This genotype-phenotype correlation could be useful from a practical clinical point of view and for future decision making.

Aims: Type 2 diabetes mellitus (T2DM) increases the risk of major cardiovascular events. In SAVOR-TIMI53 trial, the excess heart failure (HF) hospitalization among patients with T2DM in the saxagliptin group remains poorly understood. Our aim was to evaluate left ventricular (LV) diastolic function after 6 months of saxagliptin treatment using cardiac magnetic resonance imaging (CMR) in patients with T2DM., Methods: In this prospective study, 16 T2DM patients without HF were prescribed saxagliptin as part of routine guideline-directed management. CMR performed at baseline and 6 months after initiation of saxagliptin treatment were evaluated in a blinded fashion. We assessed LV diastolic function by measuring LV peak filling rate with correction for end-diastolic volume (PFR/LVEDV), time to peak filling rate with correction for cardiac cycle (TPF/RR), and early diastolic strain rate parameters [global longitudinal diastolic strain rate (GLSR-E), global circumferential diastolic strain rate (GCSR-E)] by feature tracking (FT-CMR)., Results: Among the 16 patients (mean age of 59.9, 69% males, mean hemoglobin A1c 8.3%, mean left ventricular ejection fraction 57%), mean PFR was 314 ± 108 ml/s at baseline and did not change over 6 months (- 2.7, 95% CI - 35.6, 30.2, p = 0.86). There were also no significant changes in other diastolic parameters including PFR/EDV, TPF, TPF/RR, and GLSR-E and GCSR-E (all p > 0.50)., Conclusion: In T2DM patients without HF receiving saxagliptin over 6 months, there were no significant subclinical changes in LV diastolic function as assessed by CMR., (© 2023. Springer-Verlag Italia S.r.l., part of Springer Nature.)

Coronary artery bypass graft surgery is a common intervention for coronary artery disease; however, it suffers from graft failure, and the underlying mechanisms are not fully understood. To better understand the relation between graft hemodynamics and surgical outcomes, we performed computational fluid dynamics simulations with deformable vessel walls in 10 study participants (24 bypass grafts) based on CT and 4D flow MRI one month after surgery to quantify lumen diameter, wall shear stress (WSS), and related hemodynamic measures. A second CT acquisition was performed one year after surgery to quantify lumen remodeling. Compared to venous grafts, left internal mammary artery grafts experienced lower abnormal WSS (< 1 Pa) area one month after surgery (13.8 vs. 70.1%, p = 0.001) and less inward lumen remodeling one year after surgery (- 2.4% vs. - 16.1%, p = 0.027). Abnormal WSS area one month post surgery correlated with percent change in graft lumen diameter one year post surgery (p = 0.030). This study shows for the first time prospectively a correlation between abnormal WSS area one month post surgery and graft lumen remodeling 1 year post surgery, suggesting that shear-related mechanisms may play a role in post-operative graft remodeling and might help explain differences in failure rates between arterial and venous grafts., (© 2023. The Author(s) under exclusive licence to Biomedical Engineering Society.)

Purpose: To compare the predictive value of different myocardial scar quantification thresholds using cardiac MRI for appropriate implantable cardioverter defibrillator (ICD) shock and mortality., Materials and Methods: In this retrospective, two-center observational cohort study, patients with ischemic or nonischemic cardiomyopathy underwent cardiac MRI prior to ICD implantation. Late gadolinium enhancement (LGE) was first determined visually and then quantified by blinded cardiac MRI readers using different SDs above the mean signal of normal myocardium, full-width half-maximum, and manual thresholding. The intermediate signal "gray zone" was calculated as the differences between different SDs., Results: Among 374 consecutive eligible patients (mean age, 61 years ± 13 [SD]; mean left ventricular ejection fraction, 32% ± 14; secondary prevention, 62.7%), those with LGE had a higher rate of appropriate ICD shock or death than those without (37.5% vs 26.6%, log-rank P = .04) over a median follow-up of 61 months. In multivariable analysis, none of the thresholds for quantifying scar was a significant predictor of mortality or appropriate ICD shock, while the extent of gray zone was an independent predictor (adjusted hazard ratio per 1 g = 1.025; 95% CI: 1.008, 1.043; P = .005) regardless of the presence or absence of ischemic heart disease ( P interaction = .57). Model discrimination was highest for the model incorporating the gray zone (between 2 SD and 4 SD)., Conclusion: Presence of LGE was associated with a higher rate of appropriate ICD shock or death. Although none of the scar quantification techniques predicted outcomes, the gray zone both in infarct and nonischemic scar was an independent predictor and may refine risk stratification. Keywords: MRI, Scar Quantification, Implantable Cardioverter Defibrillator, Sudden Cardiac Death Supplemental material is available for this article. © RSNA, 2023., Competing Interests: Disclosures of conflicts of interest: T.S. No relevant relationships. F.M.D.H. No relevant relationships. L.J.J. No relevant relationships. A.K. No relevant relationships. C.M.U.F. No relevant relationships. L.F. No relevant relationships. N.S.T. No relevant relationships. S.M.S. No relevant relationships. Y.G. No relevant relationships. P.D. No relevant relationships. J.A.C.L. No relevant relationships. K.C.K.W. No relevant relationships. D.P.D. No relevant relationships. A.T.Y. No relevant relationships., (© 2023 by the Radiological Society of North America, Inc.)

Thoracic aortic aneurysms (TAA) consist of abnormal dilation or the widening of a portion of the ascending aorta, due to weakness or destructuring of the walls of the vessel and are potentially lethal. The congenital bicuspid aortic valve (BAV) is considered a risk factor for the development of TAA because asymmetric blood flow through the bicuspid aortic valve detrimentally influences the wall of the ascending aorta. NOTCH1 mutations have been associated with non-syndromic TAAs as a consequence of BAV, but little is known regarding its haploinsufficiency and its relationship with connective tissue abnormalities. We report two cases in which there is clear evidence that alterations in the NOTCH1 gene are the cause of TAA in the absence of BAV. On the one hand, we describe a 117 Kb deletion that includes a large part of the NOTCH1 gene and no other coding genes, suggesting that haploinsufficiency can be considered a pathogenic mechanism for this gene associated with TAA. In addition, we describe two brothers who carry two variants, one in the NOTCH1 gene and another in the MIB1 gene, corroborating the involvement of different genes of the Notch pathway in aortic pathology.

Supplemental material is available for this article . Keywords: CT, Pulmonary Arteries, Embolism/Thrombosis, Feature Detection © RSNA, 2023., Competing Interests: Disclosures of conflicts of interest: M.F.C. No relevant relationships. H.M.L. No relevant relationships. T.H. No relevant relationships. M.A. No relevant relationships. M.N. No relevant relationships. L.J.J. No relevant relationships. R.M. No relevant relationships. S.M. No relevant relationships. D.P.D. Consultant fees on research matters pertaining to a medical device from Edwards Lifesciences totaling $25 000 to a joint departmental medical imaging research account. E.C. Support from Odette Professorship in Artificial Intelligence for Medical Imaging, St Michael’s Hospital, Unity Health Toronto, Toronto, Canada; member of the Machine Learning Steering Subcommittee of the Radiology Informatics Council for the RSNA., (© 2023 by the Radiological Society of North America, Inc.)

Although coronary artery bypass graft (CABG) surgery is a well-established intervention, graft failure can occur, and the underlying mechanisms remain incompletely understood. The purpose of this prospective study is to utilize computational fluid dynamics (CFD) to investigate how graft hemodynamics one month post surgery may vary among graft types, which have different long-term patency rates. Twenty-four grafts from 10 participants (64.6 ± 8.5 years, 9 men) were scanned with coronary CT angiography and 4D flow MRI one month after CABG surgery. Grafts included 10 left internal mammary arteries (LIMA), 3 radial arteries (RA), and 11 saphenous vein grafts (SVG). Image-guided CFD was used to quantify blood flow rate and wall area exposed to abnormal wall shear stress (WSS). Arterial grafts had a lower abnormal WSS area than venous grafts (17.9% vs. 70.1%; p = 0.001), and a similar trend was observed for LIMA vs. SVG (13.8% vs. 70.1%; p = 0.001). Abnormal WSS area correlated positively to lumen diameter (p < 0.001) and negatively to flow rate (p = 0.001). This CFD study is the first of its kind to prospectively reveal differences in abnormal WSS area 1 month post surgery among CABG types, suggesting that WSS may influence the differential long-term graft failure rates observed among these groups., (© 2022. The Author(s) under exclusive licence to Biomedical Engineering Society.)

Purpose: To design and evaluate an automated deep learning method for segmentation and analysis of cardiac MRI T1 maps with use of synthetic T1-weighted images for MRI relaxation-based contrast augmentation., Materials and Methods: This retrospective study included MRI scans acquired between 2016 and 2019 from 100 patients (mean age ± SD, 55 years ± 13; 72 men) across various clinical abnormalities with use of a modified Look-Locker inversion recovery, or MOLLI, sequence to quantify native T1 (T1 native ), postcontrast T1 (T1 post ), and extracellular volume (ECV). Data were divided into training ( n = 60) and internal ( n = 40) test subsets. "Synthetic" T1-weighted images were generated from the T1 exponential inversion-recovery signal model at a range of optimal inversion times, yielding high blood-myocardium contrast, and were used for contrast-based image augmentation during training and testing of a convolutional neural network for myocardial segmentation. Automated segmentation, T1, and ECV were compared with experts with use of Dice similarity coefficients (DSCs), correlation coefficients, and Bland-Altman analysis. An external test dataset ( n = 147) was used to assess model generalization., Results: Internal testing showed high myocardial DSC relative to experts (0.81 ± 0.08), which was similar to interobserver DSC (0.81 ± 0.08). Automated segmental measurements strongly correlated with experts (T1 native , R = 0.87; T1 post , R = 0.91; ECV, R = 0.92), which were similar to interobserver correlation (T1 native , R = 0.86; T1 post , R = 0.94; ECV, R = 0.95). External testing showed strong DSC (0.80 ± 0.09) and T1 native correlation ( R = 0.88) between automatic and expert analysis., Conclusion: This deep learning method leveraging synthetic contrast augmentation may provide accurate automated T1 and ECV analysis for cardiac MRI data acquired across different abnormalities, centers, scanners, and T1 sequences. Keywords: MRI, Cardiac, Tissue Characterization, Segmentation, Convolutional Neural Network, Deep Learning Algorithms, Machine Learning Algorithms, Supervised Learning Supplemental material is available for this article. © RSNA, 2022., Competing Interests: Disclosures of conflicts of interest: N.B. No relevant relationships. V.R. No relevant relationships. A.O. No relevant relationships. L.B. No relevant relationships. M.N. No relevant relationships. F.G. No relevant relationships. X.Q. No relevant relationships. L.G. No relevant relationships. L.J.J. No relevant relationships. I.R. No relevant relationships. G.A.W. Research grant support from GE Healthcare; stockholder in GE Healthcare. N.R.G. Grants from Ontario Research Fund (Canada) (ORF-RE7-21), Natural Sciences and Engineering Research Council (NSERC) Discovery Program (RGPIN-2019-06367) to institution., (© 2022 by the Radiological Society of North America, Inc.)

Background: To evaluate computed tomography (CT) patterns of post-SBRT lung injury in lung cancer and identify time points of serial CT changes., Materials and Methods: One hundred eighty-three tumors in 170 patients were evaluated on sequential CTs within 29 months (median). Frequencies of post-SBRT CT patterns and time points of initiation and duration were assessed. Duration of increase of primary lesion or surrounding injury without evidence of local recurrence and time to stabilization or local recurrence were evaluated., Results: Post-SBRT CT patterns could overlap in the same patient and were nodule-like pattern (69%), consolidation with ground glass opacity (GGO) (41%), modified conventional pattern (39%), peribronchial/patchy consolidation (42%), patchy GGO (24%), diffuse consolidation (16%), "orbit sign" (21%), mass-like pattern (19%), scar-like pattern (15%) and diffuse GGO (3%). Patchy GGO started at 4 months post-SBRT. Peribronchial/patchy consolidation and consolidation with GGO started at 4 and 5 months respectively. Diffuse consolidation, diffuse GGO and orbit sign started at 5, 6 and 8 months respectively. Mass-like, modified conventional and scar-like pattern started at 8, 12 and 12 months respectively. Primary lesion (n = 11) or surrounding injury (n = 85) increased up to 13 months. Primary lesion (n = 119) or surrounding injury (n = 115) started to decrease at 4 and 9 months respectively. Time to stabilization was 20 months. The most common CT pattern at stabilization was modified conventional pattern (49%), scar-like pattern (23%) and mass-like pattern (12%). Local recurrence (n = 15) occurred at a median time of 18 months., Conclusion: Different CT patterns of lung injury post-SBRT appear in predictable time points and have variable but predictable duration. Familiarity with these patterns and timeframes of appearance helps differentiate them from local recurrence., (© 2022. The Author(s).)

Although cardiac resynchronization therapy (CRT) is an established treatment for heart failure with reduced ejection fraction, 30 to 50% patients are non-responders. In this retrospective single-centre study, 19 patients underwent cardiac MRI pre-CRT, and global left ventricular (LV) strain and late gadolinium enhancement (LGE) were measured by a blinded reader. LV reverse remodeling was independently assessed using transthoracic echocardiogram before and after CRT implant. Both LV strain and extent of LGE correlated significantly with measures of reverse LV remodeling (reduction in LV volume and improvement in LV ejection fraction). These findings suggest that CMR derived strain analysis and scar evaluation may be useful preimplant predictors of response to CRT. Larger prospective multi-center studies are needed to confirm these findings and to further evaluate the role of CMR strain imaging in guiding CRT treatment decisions., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Research imaging in healthy and clinical youth populations yields incidental findings that require a management strategy. Our primary objective was to document the frequency and nature of incidental findings within a research group integrating multiple imaging modalities. A second objective was to describe the evolution of an approach to handling incidental findings. A case example was included to display the intricacies of some of these scenarios. Youth, ages 13-20 years, with bipolar disorder, familial risk for bipolar disorder, or healthy controls, obtained one or a combination of neuroimaging, cardio-thoracic imaging, retinal imaging, and carotid imaging. All images were systematically reviewed for incidental findings. Overall, of 223 participants ( n = 102 healthy controls), 59% ( n = 131) had a brain magnetic resonance imaging (MRI) incidental finding and 27% ( n = 60) had at least one incidental brain finding requiring non-urgent follow-up. In addition, of 109 participants with chest/cardiac MRI and carotid ultrasound, 3% ( n = 3) had chest findings, 2% ( n = 2) had cardiac findings, and 1% ( n = 1) had a carotid finding. Of 165 youth with retinal imaging, 1% ( n = 2) had incidental findings. While the vast majority of these incidental findings were of a non-serious, non-urgent nature, there were noteworthy exceptions. Imaging research groups need a system that emphasizes the value of clinical review of research images and one that is collaborative and responsive in order to inform follow-up plans. Rating systems that have been developed and used in neuroimaging for the classification of incidental findings can be adapted for use in areas other than the brain. Regardless of severity, incidental findings may raise anxiety in youth participants and their parents. The optimal threshold is one that balances transparency with utility., Competing Interests: PK declares his position on the advisory boards for Novartis, Alcon, Bayer, Novelty Nobility; Institutional financial support from Allergan, Bayer, Roche, Novartis; Personal financial support from Novartis, Bayer; and his position as an equity owner for ArcticDx. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Roane, Mio, Viner, Bettridge, Heyn, Roifman, Selkirk, Kertes, MacIntosh, Thayalasuthan, Detzler, Endre, Jimenez-Juan, Henry, Murray and Goldstein.)

Objectives: We evaluated left atrial (LA) remodeling using cardiac MRI (CMR) in patients with human epidermal growth factor receptor 2 (HER2)-positive breast cancer during and after trastuzumab therapy., Methods: In this prospective 2-center longitudinal study, 41 women with HER2-positive breast cancer received adjuvant trastuzumab for 12 months, in addition to standard chemotherapy. Serial CMRs were performed at baseline, 6, 12, and 18 months after initiation of trastuzumab. LA volumes were measured by a blinded reader. Linear mixed model was used to evaluate longitudinal changes., Results: Of 41 women (mean age 52 ± 11 [SD] years; 56% received anthracycline), one patient experienced trastuzumab-induced cardiotoxicity (TIC) for which trastuzumab was interrupted for one cycle. Mean baseline left ventricular ejection fraction (LVEF) was 68.0 ± 5.9% and LA ejection fraction (LAEF) was 66.0 ± 6.6%. Compared to baseline, LAEF decreased significantly at 6 months (62.7 ± 5.7%, p = 0.027) and 12 months (62.2 ± 6.1%, p = 0.003), while indexed LA minimum volume (LAmin) significantly increased at 12 months (11.6 ± 4.9 ml/m 2 vs 13.8 ± 4.5 ml/m 2 , p = 0.002). At 18 months, all changes from baseline were no longer significant. From baseline to 6 months, change in LAEF correlated with change in LVEF (Spearman's r = 0.41, p = 0.014). No significant interactions (all p > 0.10) were detected between time and anthracycline use for LA parameters., Conclusions: Among trastuzumab-treated patients with low incidence of TIC, we observed a small but significant decline in LAEF and increase in LAmin that persisted for the duration of therapy and recovered 6 months after therapy cessation. These findings suggest that trastuzumab has concurrent detrimental effects on atrial and ventricular remodeling., Key Points: • In trastuzumab-treated breast cancer patients evaluated by cardiac MRI, left atrial ejection fraction declined and minimum volume increased during treatment and recovered to baseline after trastuzumab cessation. • Changes in left atrial ejection fraction correlated with changes in left ventricular ejection fraction in the first 6 months of trastuzumab treatment. • Trastuzumab therapy is associated with concurrent detrimental effects on left atrial and ventricular remodeling., (© 2021. The Author(s), under exclusive licence to European Society of Radiology.)

Introduction: Arrhythmogenic cardiomyopathy (ACM) is an inherited disease characterized by progressive fibroadipose replacement of cardiomyocytes. Its diagnosis is based on imaging, electrocardiographic, histological and genetic/familial criteria. The development of the disease is based mainly on desmosomal genes. Knowledge of the phenotypic expression of each of these genes will help in both diagnosis and prognosis. The objective of this study is to describe the genotype-phenotype association of an unknown PKP2 gene variant in a family diagnosed with ACM., Methods: Clinical and genetic study of a big family carrying the p.Tyr168* variant in the PKP2 gene, in order to demonstrate pathogenicity of this variant, causing ACM., Results: Twenty-two patients (proband and relatives) were evaluated. This variant presented with high arrhythmic load at an early age, but without evidence of structural heart disease after 20 years of follow-up, with low risk in predictive scores. We demonstrate evidence of its pathogenicity., Conclusions: The p.Tyr168* variant in the PKP2 gene causes ACM with a high arrhythmic load and with an absence of structural heart disease. This fact emphasizes the value of knowing the phenotypic expression of each variant.

Hypertrophic cardiomyopathy (HCM) is a genetic disease characterised by increased left ventricle (LV) wall thickness caused by mutations in sarcomeric genes. Finding a causal mutation can help to better assess the proband's risk, as it allows the presence of the mutation to be evaluated in relatives and the follow-up to be focused on carriers. We performed an observational study of patients with HCM due to the novel p.Arg652Lys variant in the MYH7 gene. Eight families and 59 patients are described in the follow-up for a median of 63 months, among whom 39 (66%) carry the variant. Twenty-five (64%) of carriers developed HCM. A median maximum LV wall thickness of 16.5 mm was described. The LV hypertrophy was asymmetric septal in 75% of cases, with LV outflow tract obstruction in 28%. The incidence of a composite of serious adverse cardiovascular events (sudden death, aborted sudden death, appropriate implantable cardiac defibrillator discharge, an embolic event, or admission for heart failure) was observed in five (20%) patients. Given the finding of the p.Arg652Lys variant in patients with HCM, but not in controls, with evident segregation in patients with HCM from eight families and the location in an active site of the protein, we can define this variant as likely pathogenic and associated with the development of HCM.

Coronary artery bypass grafts (CABG) surgery is an invasive procedure performed to circumvent partial or complete blood flow blockage in coronary artery disease. In this work, we apply a numerical optimal flow control model to patient-specific geometries of CABG, reconstructed from clinical images of real-life surgical cases, in parameterized settings. The aim of these applications is to match known physiological data with numerical hemodynamics corresponding to different scenarios, arisen by tuning some parameters. Such applications are an initial step toward matching patient-specific physiological data in patient-specific vascular geometries as best as possible. Two critical challenges that reportedly arise in such problems are: (a) lack of robust quantification of meaningful boundary conditions required to match known data as best as possible and (b) high computational cost. In this work, we utilize unknown control variables in the optimal flow control problems to take care of the first challenge. Moreover, to address the second challenge, we propose a time-efficient and reliable computational environment for such parameterized problems by projecting them onto a low-dimensional solution manifold through proper orthogonal decomposition-Galerkin., (© 2020 John Wiley & Sons, Ltd.)

Dilated cardiomyopathy (DCM) has significant morbidity and mortality. Familial transmission is reported in 20-35% of cases, highlighting the role of genetics in this disorder. We present an interesting family in which the index case is a 64-year-old woman who survived a sudden cardiac arrest. She presented left ventricular dilatation and dysfunction, which indicated the presence of DCM, as well as a history of DCM and sudden arrest in her family (mother and sister). Genetic testing identified a heterozygous mutation c.74A > G missense change that causes an amino acid, p.Glu25Gly, change in the N-terminal domain of the SCN5A protein. After performing an exhaustive family medical history, we found that this previously not described mutation segregated within the family. All relatives with the DCM phenotype were carriers, whereas none of the noncarriers showed signs of heart disease, so this mutation is the most likely cause of the disease. This is the first time that a variant in the N-terminal domain of SCN5A has been associated with DCM.

Background Right ventricular ejection fraction (RVEF) is an independent predictor of death and adverse cardiovascular outcomes in patients with various cardiac conditions. Purpose To investigate whether RVEF, measured with cardiac MRI, is a predictor of appropriate shock or death in implantable cardioverter-defibrillator (ICD) recipients for primary and secondary prevention of sudden cardiac death. Materials and Methods This retrospective, multicenter, observational study included patients who underwent cardiac MRI before ICD implantation between January 2007 and May 2017. Right ventricular end-diastolic and end-systolic volumes and RVEF were measured with cardiac MRI. The primary end point was a composite of all-cause mortality or appropriate ICD shock. The secondary end point was all-cause mortality. The association between RVEF and primary and secondary outcomes was evaluated by using multivariable Cox regression analysis. Potential interactions were tested between primary prevention, ischemic cause, left ventricular ejection fraction (LVEF), and RVEF. Results Among 411 patients (mean age ± standard deviation, 60 years; 315 men) during a median follow-up of 63 months, 143 (35%) patients experienced an appropriate ICD shock or died. In univariable analysis, lower RVEF was associated with greater risks for appropriate ICD shock or death and for death alone (log-rank trend test, P = .003 and .005 respectively). In multivariable Cox regression analysis adjusting for age at ICD implantation, LVEF, ICD indication (primary vs secondary), ischemic heart disease, and late gadolinium enhancement, RVEF was an independent predictor of the primary outcome (hazard ratio [HR], 1.21 per 10% lower RVEF; 95% CI: 1.04, 1.41; P = .01) and all-cause mortality (HR, 1.25 per 10% lower RVEF; 95% CI: 1.01, 1.55; P = .04). No evidence of significant interactions was found between RVEF and primary or secondary prevention ( P = .49), ischemic heart disease ( P = .78), and LVEF ( P = .29). Conclusion Right ventricular ejection fraction measured with cardiac MRI was a predictor of appropriate implantable cardioverter-defibrillator shock or death. © RSNA, 2021 See also the editorial by Nazarian and Zghaib in this issue. An earlier incorrect version of this article appeared online. This article was corrected on August 24, 2021.

The authors report a 27-year-old woman with a remote left femoral osteosarcoma and amputation above the left knee who presented with a large right ventricular mass. Initial evaluation with thoracic CT was inconclusive regarding thrombus versus tumor, but metastatic osteosarcoma was suggested by findings at transthoracic echocardiography, cardiac CT, and cardiac MRI. The patient underwent tumor debulking, and osteosarcoma was confirmed with pathologic examination. She responded to chemotherapy, which resulted in reduction in size of the residual right ventricular tumor and of a few pulmonary metastases. Following induction chemotherapy, patient remains well undergoing maintenance therapy with an oral tyrosine kinase inhibitor. Keywords: CT, Echocardiography, MR Imaging, Intraoperative, Cardiac, Heart, Right Ventricle, Imaging Sequences, Metastases, Oncology Supplemental material is available for this article. © RSNA, 2021., Competing Interests: Disclosures of conflicts of interest: B.B. No relevant relationships. H.S.I. No relevant relationships. F.M.A. No relevant relationships. B.S. No relevant relationships. T.V. No relevant relationships. L.J.J. No relevant relationships. A.G. No relevant relationships. A.T.Y. No relevant relationships. D.M. No relevant relationships. G.O. No relevant relationships. D.A.L. Consultancy fees from Xylor Therapeutics (unrelated). E.T.N. No relevant relationships. M.A.S. No relevant relationships. R.J.C. Volunteer position as member of patient safety workforce committee at Society of Thoracic Surgeons. D.P.D. No relevant relationships., (2021 by the Radiological Society of North America, Inc.)

Background: Cardiovascular magnetic resonance (CMR) is increasingly used in the evaluation of patients who are potential candidates for implantable cardioverter-defibrillator (ICD) therapy to assess left ventricular (LV) ejection fraction (LVEF), myocardial fibrosis, and etiology of cardiomyopathy. It is unclear whether CMR-derived strain measurements are predictive of appropriate shocks and death among patients who receive an ICD. We evaluated the prognostic value of LV strain parameters on feature-tracking (FT) CMR in patients who underwent subsequent ICD implant for primary or secondary prevention of sudden cardiac death., Methods: Consecutive patients from 2 Canadian tertiary care hospitals who underwent ICD implant and had a pre-implant CMR scan were included. Using FT-CMR, a single, blinded, reader measured LV global longitudinal (GLS), circumferential (GCS), and radial (GRS) strain. Cox proportional hazards regression was performed to assess the associations between strain measurements and the primary composite endpoint of all-cause death or appropriate ICD shock that was independently ascertained., Results: Of 364 patients (mean 61 years, mean LVEF 32%), 64(17.6%) died and 118(32.4%) reached the primary endpoint over a median follow-up of 62 months. Univariate analyses showed significant associations between GLS, GCS, and GRS and appropriate ICD shocks or death (all p < 0.01). In multivariable Cox models incorporating LVEF, GLS remained an independent predictor of both the primary endpoint (HR 1.05 per 1% higher GLS, 95% CI 1.01-1.09, p = 0.010) and death alone (HR 1.06 per 1% higher GLS, 95% CI 1.02-1.11, p = 0.003). There was no significant interaction between GLS and indication for ICD implant, presence of ischemic heart disease or late gadolinium enhancement (all p > 0.30)., Conclusions: GLS by FT-CMR is an independent predictor of appropriate shocks or mortality in ICD patients, beyond conventional prognosticators including LVEF. Further study is needed to elucidate the role of LV strain analysis to refine risk stratification in routine assessment of ICD treatment benefit., (© 2021. The Author(s).)

The choice of appropriate boundary conditions is a fundamental step in computational fluid dynamics (CFD) simulations of the cardiovascular system. Boundary conditions, in fact, highly affect the computed pressure and flow rates, and consequently haemodynamic indicators such as wall shear stress (WSS), which are of clinical interest. Devising automated procedures for the selection of boundary conditions is vital to achieve repeatable simulations. However, the most common techniques do not automatically assimilate patient-specific data, relying instead on expensive and time-consuming manual tuning procedures. In this work, we propose a technique for the automated estimation of outlet boundary conditions based on optimal control. The values of resistive boundary conditions are set as control variables and optimized to match available patient-specific data. Experimental results on four aortic arches demonstrate that the proposed framework can assimilate 4D-Flow MRI data more accurately than two other common techniques based on Murray's law and Ohm's law., (© 2021 The Authors. International Journal for Numerical Methods in Biomedical Engineering published by John Wiley & Sons Ltd.)

Left atrial (LA) volume and function (LA ejection fraction, LAEF) have demonstrated prognostic value in various cardiovascular diseases. We investigated the incremental value of LA volume and LAEF as measured by cardiovascular magnetic resonance imaging (CMR) for prediction of appropriate implantable cardioverter defibrillator (ICD) shock or all-cause mortality, in patients with ICD. We conducted a retrospective, multi-centre observational cohort study of patients who underwent CMR prior to primary or secondary prevention ICD implantation. A single, blinded reader measured maximum LA volume index (maxLAVi), minimum LA volume index (minLAVi), and LAEF. The primary outcome was a composite of independently adjudicated appropriate ICD shock or all-cause death. A total of 392 patients were enrolled. During a median follow-up time of 61 months, 140 (35.7%) experienced an appropriate ICD shock or died. Higher maxLAVi and minLAVi, and lower LAEF were associated with greater risk of appropriate ICD shock or death in univariate analysis. However, in multivariable analysis, LAEF (HR 0.92 per 10% higher, 95% CI 0.81-1.04, p = 0.17) and maxLAVi (HR 1.02 per 10 ml/m 2 higher, 95% CI 0.93-1.12, p = 0.72) were not independent predictors of the primary outcome. In conclusion, LA volume and function measured by CMR were univariate but not independent predictors of appropriate ICD shocks or mortality. These findings do not support the routine assessment of LA volume and function to refine risk stratification to guide ICD implant. Larger studies with longer follow-up are required to further delineate the clinical implications of LA size and function., (© 2021. The Author(s), under exclusive licence to Springer Nature B.V. part of Springer Nature.)

The NKX2-5 gene encodes for a transcription factor crucial for cardiac cell differentiation and proliferation. It was the first gene associated with congenital heart disease (CHD) in humans and has been linked to conduction disorders or cardiomyopathies. However, an overlapping phenotype is not frequent in the literature. We describe a family with a novel missense mutation in the NKX2-5 gene (p.Gln181Pro) with numerous antecedents with atrial septal defect (ASD), left ventricular non-compaction (LVNC), conduction disease, and sudden cardiac death (SCD)., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Morlanes-Gracia, Antoniutti, Alvarez-Rubio, Torres-Juan, Heine-Suñer and Ripoll-Vera.)

Background: Current indications for implantable cardioverter defibrillator (ICD) implantation for sudden cardiac death prevention rely primarily on left ventricular (LV) ejection fraction (LVEF). Currently, two different contouring methods by cardiovascular magnetic resonance (CMR) are used for LVEF calculation. We evaluated the comparative prognostic value of these two methods in the ICD population, and if measures of LV geometry added predictive value., Methods: In this retrospective, 2-center observational cohort study, patients underwent CMR prior to ICD implantation for primary or secondary prevention from January 2005 to December 2018. Two readers, blinded to all clinical and outcome data assessed CMR studies by: (a) including the LV trabeculae and papillary muscles (TPM) (trabeculated endocardial contours), and (b) excluding LV TPM (rounded endocardial contours) from the total LV mass for calculation of LVEF, LV volumes and mass. LV sphericity and sphere-volume indices were also calculated. The primary outcome was a composite of appropriate ICD shocks or death., Results: Of the 372 consecutive eligible patients, 129 patients (34.7%) had appropriate ICD shock, and 65 (17.5%) died over a median duration follow-up of 61 months (IQR 38-103). LVEF was higher when including TPM versus excluding TPM (36% vs. 31%, p < 0.001). The rate of appropriate ICD shock or all-cause death was higher among patients with lower LVEF both including and excluding TPM (p for trend = 0.019 and 0.004, respectively). In multivariable models adjusting for age, primary prevention, ischemic heart disease and late gadolinium enhancement, both LVEF (HR per 10% including TPM 0.814 [95%CI 0.688-0.962] p = 0.016, vs. HR per 10% excluding TPM 0.780 [95%CI 0.639-0.951] p = 0.014) and LV mass index (HR per 10 g/m 2 including TPM 1.099 [95%CI 1.027-1.175] p = 0.006; HR per 10 g/m 2 excluding TPM 1.126 [95%CI 1.032-1.228] p = 0.008) had independent prognostic value. Higher LV end-systolic volumes and LV sphericity were significantly associated with increased mortality but showed no added prognostic value., Conclusion: Both CMR post-processing methods showed similar prognostic value and can be used for LVEF assessment. LVEF and indexed LV mass are independent predictors for appropriate ICD shocks and all-cause mortality in the ICD population.

Certain entities may simultaneously involve the lungs and the myocardium. Knowing their cardiac and thoracic manifestations enhances the understanding of those conditions and increases awareness and suspicion for possible concurrent cardiothoracic involvement. Entities that can present with pulmonary and myocardial involvement include infiltrative diseases like sarcoidosis and amyloidosis, eosinophil-associated conditions including eosinophilic granulomatosis with polyangiitis (EGPA) and hypereosinophilic syndrome (HES), connective tissue diseases such as systemic sclerosis (SSc) and lupus erythematosus and genetic disorders like Fabry disease (FD). Lung involvement in sarcoidosis is almost universal. While cardiac involvement is less common, concurrent cardiothoracic involvement can often be seen. Pulmonary amyloidosis is more often a localized process and generally occurs separately from cardiac involvement, except for diffuse alveolar-septal amyloidosis. EGPA and HES can present with consolidative or ground glass opacities, cardiac inflammation and endomyocardial fibrosis. Manifestations of SSc include interstitial lung disease, pulmonary hypertension and cardiomyopathy. Lupus can present with serositis, pneumonitis and cardiac inflammation. FD causes left ventricular thickening and fibrosis, and small airways disease. This article aims to review the clinicopathological features of chest and cardiac involvement of these entities and describe their main findings on chest CT and cardiac MR., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Quantitative measurement of lung perfusion is a promising tool to evaluate lung pathophysiology as well as to assess disease severity and monitor treatment. However, this novel technique has not been adopted clinically due to various technical and physiological challenges; and it is still in the early developmental phase where the correlation between lung pathophysiology and perfusion maps is being explored. The purpose of this research work is to quantify the impact of pulmonary artery occlusion on lung perfusion indices using lung dynamic perfusion CT (DPCT). We performed Lung DPCT in ten anesthetized, mechanically ventilated juvenile pigs (18.6-20.2 kg) with a range of reversible pulmonary artery occlusions (0%, 40-59%, 60-79%, 80-99%, and 100%) created with a balloon catheter. For each arterial occlusion, DPCT data was analyzed using first-pass kinetics to derive blood flow (BF), blood volume (BV) and mean transit time (MTT) perfusion maps. Two radiologists qualitatively assessed perfusion maps for the presence or absence of perfusion defects. Perfusion maps were also analyzed quantitatively using a linear segmented mixed model to determine the thresholds of arterial occlusion associated with perfusion derangement. Inter-observer agreement was assessed using Kappa statistics. Correlation between arterial occlusion and perfusion indices was evaluated using the Spearman-rank correlation coefficient. Our results determined that perfusion defects were detected qualitatively in BF, BV and MTT perfusion maps for occlusions larger than 55%, 80% and 55% respectively. Inter-observer agreement was very good with Kappa scores > 0.92. Quantitative analysis of the perfusion maps determined the arterial occlusion threshold for perfusion defects was 50%, 76% and 44% for BF, BV and MTT respectively. Spearman-rank correlation coefficients between arterial occlusion and normalized perfusion values were strong (- 0.92, - 0.72, and 0.78 for BF, BV and MTT, respectively) and were statically significant (p < 0.01). These findings demonstrate that lung DPCT enables quantification and stratification of pulmonary artery occlusion into three categories: mild, moderate and severe. Severe (occlusion ≥ 80%) alters all perfusion indices; mild (occlusion < 55%) has no detectable effect. Moderate (occlusion 55-80%) impacts BF and MTT but BV is preserved.

Since the advent of multidetecter computed tomography (CT), radiologist sensitivity in detection of traumatic bowel and mesenteric abnormalities has significantly improved. Although several CT signs have been described to identify intestinal injury, accurate interpretation of these findings can remain challenging. Early detection of bowel and mesenteric injury is important as it alters patient management, disposition, and follow-up. This article reviews the common imaging findings of traumatic small bowel and mesenteric injury.

A 75-year-old male with a cardiopulmonary history presented with chest pain and dyspnea. He was hypertensive. An electrocardiogram showed paced rhythm. A high-sensitivity test showed his troponin T level was minimally elevated. Coronary angiography results were unremarkable. Chest radiography revealed an elevated cardiac apex, previously attributed to cardiomegaly. Echocardiography revealed a teardrop shaped heart in a nonstandard apical window. Computed tomography confirmed congenital absence of the left pericardium. Challenges of recognizing a rare condition are highlighted. Congenital absence of the pericardium, an often benign but rarely catastrophic condition, can masquerade for decades before diagnosis, underlining the importance of clinical vigilance in evaluating common cardiac complaints., (© 2020 Canadian Cardiovascular Society. Published by Elsevier Inc.)

Background: Conversion from conventional hemodialysis (CHD) to in-centre nocturnal hemodialysis (INHD) is associated with left ventricular (LV) mass regression, but the underlying mechanisms are not fully understood. Using cardiac MRI (CMR), we examined the effects of INHD on epicardial adipose tissue (EAT) and paracardial adipose tissue (PAT), and the relationships between EAT, PAT and LV remodeling, biomarkers of nutrition, myocardial injury, fibrosis and volume., Methods: We conducted a prospective multicenter cohort study of 37 patients transitioned from CHD to INHD and 30 patients on CHD (control). Biochemical markers and CMR were performed at baseline and 52 weeks. CMR images were analyzed by independent readers, blinded to order and treatment group., Results: Among 64 participants with complete CMR studies at baseline (mean age 54; 43% women), there were no significant differences in EAT index (60.6 ± 4.3 mL/m 2 vs 64.2 ± 5.1 mL/m 2 , p = 0.99) or PAT index (60.0 ± 5.4 mL/m 2 vs 53.2 ± 5.9 mL/m 2 , p = 0.42) between INHD and CHD groups. Over 52 weeks, EAT index and PAT index did not change significantly in INHD and CHD groups (p = 0.21 and 0.14, respectively), and the changes in EAT index and PAT index did not differ significantly between INHD and CHD groups (p = 0.30 and 0.16, respectively). Overall, changes in EAT index inversely correlated with changes in LV end-systolic volume index (LVESVI) but not LV end-diastolic volume index (LVEDVI), LV mass index (LVMI), and LV ejection fraction (LVEF). Changes in PAT index inversely correlated with changes in LVESVI, LVMI and positively correlated with changes in LVEF. There were no correlations between changes in EAT index or PAT index with changes in albumin, LDL, triglycerides, troponin-I, FGF-23, or NT-proBNP levels over 52 weeks (all p > 0.30)., Conclusions: INHD was not associated with any changes in EAT index and PAT index over 12 months. Changes in EAT index were not significantly associated with changes in markers of LV remodeling, nutrition, myocardial injury, fibrosis, volume status. In contrast, changes in PAT index, which paradoxically is expected to exert less paracrine effect on the myocardium, were correlated with changes in LVESVI, LVMI and LVEF. Larger and longer-term studies may clarify the role of PAT in cardiac remodeling with intensified hemodialysis. CLINICALTRIALS., Gov Identifier: NCT00718848.

In Argentina, Leishmania infantum (syn. L. chagasi ) is the etiologic agent of human visceral leishmaniosis (HVL), and Lutzomyia longipalpis (Diptera: Psychodidae: Phlebotominae) is the main vector. The objective of this study was to evaluate the effectiveness and residual effect of two commercial insecticide formulations, one with permethrin and pyriproxyfen as active ingredients (Dragon Max®) and the other with only permethrin (Flop®) for the control of sandflies. Both formulations were applied in chicken coops and other surroundings structures of the peridomicile of urban houses in Clorinda, Formosa (Argentina). Entomological monitoring was carried out weekly for 44 weeks after the intervention. The results showed great effectiveness and residual effect up to 21 weeks post-intervention for Dragon Max®. This result could be explained by the excellent larvicidal activity of the Insect Growth Regulator (IGR) pyriproxyfen against the immature forms of phlebotomines and by the delay on the restoration of the natural threshold of the vector population in treated sites.

Aim: Intensified haemodialysis is associated with regression of left ventricular (LV) mass. Compared to LV ejection fraction, LV strain allows more direct assessment of LV function. We sought to assess the impact of in-centre nocturnal haemodialysis (INHD) on global LV strain (radial, circumferential, and longitudinal) and torsion by cardiac MRI (CMR)., Methods: In this prospective, two-centre cohort study, 37 participants on conventional haemodialysis (CHD, 3-4 h/session for three sessions/week) converted to INHD (7-8 h/session for three sessions/week) and 30 participants continued CHD. Participants underwent CMR using a standardized protocol and had biomarker measurements at baseline and 52 weeks., Results: Among the 55 participants (mean age 55; 40% women) with complete CMR data, those who converted to INHD had a significant improvement in their global circumferential strain (GCS, P = 0.025), while those continuing CHD did not have any significant changes in LV strain. When the two groups were compared, there was significant improvement in torsion. LV strains were significantly correlated with each other, but not with troponin I, C-reactive protein, or brain natriuretic protein (NT-proBNP), except for global longitudinal strain (GLS) with troponin I (P = 0.001) and NT-proBNP (P = 0.038)., Conclusion: Conversion to INHD was associated with significant improvement in GCS over one year of study, although comparisons with the CHD group were not significant. There was also a significant decrease in torsion in the INHD group compared with CHD. Improvement in LV regional function would support the notion that INHD has favourable effects on both LV structure and function., (© 2018 Asian Pacific Society of Nephrology.)

Our aim was to evaluate the temporal changes in left ventricular (LV) diastolic filling in relation to other LV parameters using cardiac MRI (CMR) in patients with HER2 positive breast cancer receiving trastuzumab therapy. Fourty-one women with early stage HER2+ breast cancer underwent serial CMR (baseline, 6, 12, and 18 months) after initiation of trastuzumab therapy. A single, blinded observer measured LV parameters on de-identified CMRs in random order. Linear mixed models were used to investigate temporal changes. Compared to baseline, there were significant decreases in systolic function as measured by both left ventricular ejection fraction (LVEF) (p <0.001 at 6 and 12 months) and peak ejection rate corrected for end-diastolic volume (PER/LVEDV) (p = 0.008 at 6 months, p = 0.01 at 12 months). However, these differences were no longer significant at 18 months. In contrast, significant reductions in diastolic function as measured by LV peak filling rate corrected for end-diastolic volume (PFR/LVEDV) were observed at 6 months (p = 0.012), 12 months (p = 0.031), and up to 18 months (p = 0.034). There were no significant temporal changes in the time to peak filling rate corrected for cardiac cycle (TPF/RR). The reduction in PFR/LVEDV at 18 months was no longer significant when corrected for heart rate. In conclusion, there were significant subclinical deleterious effects on both LV systolic and diastolic function among patients receiving trastuzumab. While there was recovery in LV systolic function after therapy cessation at 18 months, reduction in PFR/LVEDV appeared to persist. Thus, diastolic dysfunction may serve as a marker of trastuzumab-induced cardiotoxicity that needs to be confirmed in a larger study., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Objective: This study aims to determine an appropriate timeline to monitor indeterminate pulmonary nodules (IPN) in melanoma patients to confirm metastatic origin., Materials and Methods: 588 clinically non-metastatic melanoma patients underwent curative intent surgery during 3 years. Patients with baseline chest CT and at least one follow-up (FU) CT were retrospectively analyzed to assess for IPN. Patients with definitely benign nodules, metastases and non-melanoma malignancies were excluded. Change in volume from first to FU CT, initial diameter (D1) and volume (V1), distance from pleura, peripheral and perifissural location, density and clinical stage were evaluated. Nodules were volumetrically measured on CTs and were considered metastases if they increased in size between two CTs or if increase was accompanied by multiple new nodules or extrapulmonary metastases., Results: 148 patients were included. Two out of 243 baseline IPN detected in 70 patients, increased significantly in volume in 3 and 5 months and were proven metastases. During FU, 86% of 40 interval IPN detected in 28 patients, were proven metastases. Interval nodule (p < 0.0001, HR:243,CI:[57.32,1033.74]), 3-month volume change (OR:1.023,CI:[1.014,1.033]), V1 (OR:1.006,CI:[1.003,1.009]), D1 (OR:1.424,CI:[1.23,1.648]), distance from pleura (OR:1.03,CI:[1.003,1.059]), and combined stage IIC + III (OR:11.29,CI:[1.514,84.174]), were associated with increased risk for metastasis. 43%, 72% and 94% of patients with IPN were confirmed with metastases in the first FU CT at 3, 6 and 12 months respectively., Conclusion: Baseline IPN are most likely benign, while interval IPN are high risk for metastasis. Absence of volume increase of IPN within 6 months excluded metastasis in most patients.

Objective: Pneumothorax development can cause precipitous deterioration in ICU patients, therefore quick and accurate detection is vital. Portable chest radiography is commonly performed to exclude pneumothoraces but is hampered by supine patient position and overlying internal and external material. Also, the initial evaluation of the chest radiograph may be performed by a relatively inexperienced physician. Therefore, a tool that could significantly improve pneumothorax detection on portable radiography would be helpful in patient care. The aim of this study was to evaluate the clinical utility of novel enhancement software for pneumothorax detection in readers with varied clinical experience of detecting/excluding pneumothoraces on portable chest radiographs in ICU patients., Subjects and Methods: 206 portable ICU chest radiographs, 103 with pneumothoraces, were processed with and without enhancement software and reviewed by 5 readers who varied in reading experience. Images were grouped for different complexity levels., Results: The mean AUC for pneumothorax detection increased for 4/5 readers from 0.846-0.957 to 0.88-0.971 with a largest improvement for the reader with least experience. No significant change was noted for the reader with the longest reading experience. The image complexity had no impact on the interpretation result., Conclusion: Pneumothorax detection improves with novel enhancement software; the largest improvement is seen in less experienced readers., Competing Interests: Dr Narinder Paul receives research grant support from Carestream Health. This study was not funded by Carestream Health. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Objectives: Cardiovascular magnetic resonance (CMR) imaging is the gold-standard test for the assessment of heart function. Despite its importance, many jurisdictions lack specific billing codes that can be used to identify patient receipt of CMR in administrative databases, limiting the ability to perform 'big data' CMR studies. Our objective was to identify the optimal billing code combination to identify patients who underwent CMR using administrative data in Ontario., Design: Retrospective cohort study., Setting: Quaternary care academic referral centre in Ontario, Canada., Participants: We tested all billing code combinations in order to identify the optimal one to determine receipt of CMR. The reference gold standard was a list of all cardiothoracic magnetic resonance scans performed at Sunnybrook Health Sciences Centre between 1 January 2014 and 31 December 2016, verified by chart audit. We assessed the diagnostic performance (accuracy, sensitivity, specificity, positive predictive value and negative predictive value) for all code combinations., Results: Our gold-standard cohort consisted of 2339 thoracic MRIs that were performed at Sunnybrook Health Sciences Centre from 1 January 2014 to 31 December 2016. Of these, 2139 (91.5%) were CMRs and 200 (8.5%) were chest MRIs. We identified the most accurate billing combination for the determination of patient receipt of CMR. This combination resulted in an accuracy of 95.3% (95% CI 94.4% to 96.2%), sensitivity of 97.4% (95% CI 96.6% to 98.1%), specificity of 86.4% (95% CI 83.1% to 89.6%), positive predictive value of 96.9% (95% CI 96.1% to 97.6%) and negative predictive value of 88.4% (95% CI 85.4% to 91.5%)., Conclusions: Our study is the first to verify the ability to accurately identify patient receipt of CMR using administrative data, facilitating more robust population-based CMR studies in the future., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2018. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: Current guidelines provide left ventricular ejection fraction (LVEF) criterion for use of implantable cardioverter defibrillators (ICD) but do not specify which modality to use for measurement. We compared LVEF measurements by radionuclide ventriculography (RNV) vs cardiac MRI (CMR) in ICD candidates to assess impact on clinical decision making., Methods: This single-centre study included 124 consecutive patients referred for assessment of ICD implantation who underwent RNV and CMR within 30 days for LVEF measurement. RNV and CMR were interpreted independently by experienced readers., Results: Among 124 patients (age 64 ± 11 years, 77% male), median interval between CMR and RNV was 1 day; mean LVEF was 32 ± 12% by CMR and 33 ± 11% by RNV (p = 0.60). LVEF by CMR and RNV showed good correlation, but Bland-Altman analysis showed relatively wide limits of agreement (-12.1 to 11.4). CMR LVEF reclassified 26 (21%) patients compared to RNV LVEF (kappa = 0.58). LVEF by both modalities showed good interobserver reproducibility (ICC 0.96 and 0.94, respectively) (limits of agreement -7.27 to 5.75 and -8.63 to 6.34, respectively)., Conclusion: Although LVEF measurements by CMR and RNV show moderate agreement, there is frequent reclassification of patients for ICD placement based on LVEF between these modalities. Future studies should determine if a particular imaging modality for LVEF measurement may enhance ICD decision making and treatment benefit., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: In-center nocturnal hemodialysis (INHD) is associated with favorable left ventricular (LV) remodeling. Although right ventricular (RV) structure and function carry prognostic significance, the impact of dialysis intensification on RV is unknown. Our objectives were to evaluate changes in RV mass index (MI), end-diastolic volume index (EDVI), end-systolic volume index (ESVI) and ejection fraction (EF) after conversion to INHD and their relationship with LV remodeling., Methods: Of 67 conventional hemodialysis (CHD, 4 h/session, three times/week) patients, 30 continued on CHD and 37 converted to INHD (7-8 h/session, three times/week). Cardiac magnetic resonance imaging was performed at baseline and 1 year using a standardized protocol; an experienced and blinded reader performed RV measurements., Results: At 1 year there were significant reductions in RVMI {-2.1 g/m2 [95% confidence interval (CI) -3.8 to - 0.4], P = 0.017}, RVEDVI [-9.5 mL/m2 (95% CI - 16.3 to - 2.6), P = 0.008] and RVESVI [-6.2 mL/m2 (95% CI - 10.9 to - 1.6), P = 0.011] in the INHD group; no significant changes were observed in the CHD group. Between-group comparisons showed significantly greater reduction of RVESVI [-7.9 mL/m2 (95% CI - 14.9 to - 0.9), P = 0.03] in the INHD group, a nonsignificant trend toward greater reduction in RVEDVI and no significant difference in RVMI and RVEF changes. There was significant correlation between LV and RV in terms of changes in mass index (MI) (r = 0.46), EDVI (r = 0.73), ESVI (r = 0.7) and EF (r = 0.38) over 1 year (all P < 0.01)., Conclusions: Conversion to INHD was associated with a significant reduction of RVESVI. Temporal changes in RV mass, volume and function paralleled those of LV. Our findings support the need for larger, longer-term studies to confirm favorable RV remodeling and determine its impact on clinical outcomes.

We sought to quantify contribution of radiomics and SUVmax at PET/CT to predict clinical outcome in lung cancer patients treated with stereotactic body radiotherapy (SBRT). 150 patients with 172 lung cancers, who underwent SBRT were retrospectively included. Radiomics were applied on PET/CT. Principal components (PC) for 42 CT and PET-derived features were examined to determine which ones accounted for most of variability. Survival analysis quantified ability of radiomics and SUVmax to predict outcome. PCs including homogeneity, size, maximum intensity, mean and median gray level, standard deviation, entropy, kurtosis, skewness, morphology and asymmetry were included in prediction models for regional control (RC) [PC4-HR:0.38, p = 0.02], distant control (DC) [PC4-HR:0.51, p = 0.02 and PC1-HR:1.12, p = 0.01], recurrence free probability (RFP) [PC1-HR:1.08, p = 0.04], disease specific survival (DSS) [PC2-HR:1.34, p = 0.03 and PC3-HR:0.64, p = 0.02] and overall survival (OS) [PC4-HR:0.45, p = 0.004 and PC3-HR:0.74, p = 0.02]. In combined analysis with SUVmax, PC1 lost predictive ability over SUVmax for RFP [HR:1.1, p = 0.04] and DC [HR:1.13, p = 0.002], while PC4 remained predictive of DC independent of SUVmax [HR:0.5, p = 0.02]. Radiomics remained the only predictors of OS, DSS and RC. Neither SUVmax nor radiomics predicted recurrence free survival. Radiomics on PET/CT provided complementary information for prediction of control and survival in SBRT-treated lung cancer patients.

Over the past 25 years, cardiovascular magnetic resonance imaging (CMR) has developed into an increasingly valuable imaging modality. CMR is now a routine clinical tool for the evaluation of cardiovascular structure and function. However, current patterns in the utilization of CMR in Canada are unknown as are data on important issues such as wait times and appropriate use of this technology. To address these issues, we sought to perform a staged pan-Canadian Survey to initiate dialogue regarding the utilization and appropriate use of CMR in Canada. Two surveys were sent out to participants involved with the performance of CMR at tertiary care referral centres across Canada, one in 2015 and the other in 2017. Questions for both surveys were vetted by the executive committee of the Canadian Society for Cardiovascular Magnetic Resonance and were distributed to sites identified through Canadian Society for Cardiovascular Magnetic Resonance memberships. Descriptive statistics were used to summarize data. Twenty-one sites participated in the 2015 survey and 17 in the 2017 survey. Our results highlighted that most participants believe that CMR is an important component in the clinical decision-making process. They also exposed important issues such as excessive and seemingly worsening wait times for CMR and suggested potential drivers of this phenomenon. Finally, our results confirm ongoing challenges in the imaging community in meeting quality assurance guidelines aimed at documenting appropriate use criteria. Researchers and policy makers should focus on mechanisms aimed to reduce wait times as well as increase use of appropriate use criteria., (Copyright © 2018 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.)

Objective: Diastolic dysfunction is common in hypertrophic cardiomyopathy (HCM) and hypertensive heart disease (HHD), but its relationships with left ventricular (LV) parameters have not been well studied. Our objective was to assess the relationship of various measures of diastolic function, and maximum left ventricular wall thickness (MLVWT) and left ventricular mass index (LVMI) in HCM, HHD and normal controls using cardiac magnetic resonance imaging (CMR). We also assessed LV parameters and diastolic function in relation to late gadolinium enhancement (LGE) and right ventricular (RV) hypertrophy in HCM., Methods: 41 patients with HCM, 21 patients with HHD and 20 controls were studied. Peak filling rate (PFR), time to peak filling (TPF), MLVWT and LVMI were measured using CMR. LGE and RV morphology were assessed in HCM patients., Results: MLVWT correlated with TPF in HCM (r=0.38; p=0.02), HHD (r=0.58; p=0.01) and controls (r=0.54; p=0.01); correlation between MLVWT and TPF was weaker in HCM than HHD. LVMI did not correlate with diastolic function. In HCM, LGE extent correlated with MLVWT (τ=0.41; p=0.002) and with TPF (τ=0.29; p=0.02). The HCM patients with RV hypertrophy had higher MLVWT (p<0.001) and TPF (p=0.03) than patients without RV hypertrophy., Conclusion: MLVWT correlates with diastolic function (TPF) in HCM, HHD and controls. LVMI did not show significant correlation with TPF. The diastolic dysfunction in HCM is not entirely explained by wall thickening. LGE and RV involvement are associated with worse LV diastolic function, suggesting that these may be markers of more severe underlying myocardial disarray and fibrosis that contribute to diastolic dysfunction., (Copyright © 2016. Published by Elsevier B.V.)

Background: There are limited data on the effects of trastuzumab on the right ventricle (RV). Therefore, we sought to evaluate the temporal changes in right ventricular (RV) structure and function as measured by cardiovascular magnetic resonance (CMR), and their relationship with left ventricular (LV) structure and function in breast cancer patients treated with trastuzumab., Methods: Prospective, longitudinal, observational study involving 41 women with HER2+ breast cancer who underwent serial CMR at baseline, 6, 12, and 18 months after initiation of trastuzumab. A single blinded observer measured RV parameters on de-identified CMRs in a random order. Linear mixed models were used to investigate temporal changes in RV parameters., Results: Of the 41 women (age 52 ± 11 years), only one patient experienced trastuzumab-induced cardiotoxicity. Compared to baseline, there were small but significant increases in the RV end-diastolic volume at 6 months (p = 0.002) and RV end-systolic volume at 6 and 12 months (p < 0.001 for both), but not at 18 months (p = 0.82 and 0.13 respectively). RV ejection fraction (RVEF), when compared to baseline (58.3%, 95% CI 57.1-59.5%), showed corresponding decreases at 6 months (53.9%, 95% CI 52.5-55.4%, p < 0.001) and 12 months (55%, 95% CI 53.8-56.2%, p < 0.001) that recovered at 18 months (56.6%, 95% CI 55.1-58.0%, p = 0.08). Although the temporal pattern of changes in LVEF and RVEF were similar, there was no significant correlation between RVEF and LVEF at baseline (r = 0.29, p = 0.07) or between their changes at 6 months (r = 0.24, p = 0.17)., Conclusion: In patients receiving trastuzumab without overt cardiotoxicity, there is a subtle but significant deleterious effect on RV structure and function that recover at 18 months, which can be detected by CMR. Furthermore, monitoring of LVEF alone may not be sufficient in detecting early RV injury. These novel findings provide further support for CMR in monitoring early cardiotoxicity., Trial Registration: ClinicalTrials.gov Identifier: NCT01022086 . Date of registration: November 27, 2009.

Background: Indications for the primary prevention of sudden death using an implantable cardioverter defibrillator (ICD) are based predominantly on left ventricular ejection fraction (LVEF). However, right ventricular ejection fraction (RVEF) is also a known prognostic factor in a variety of structural heart diseases that predispose to sudden cardiac death. We sought to investigate the relationship between right and left ventricular parameters (function and volume) measured by cardiovascular magnetic resonance (CMR) among a broad spectrum of patients considered for an ICD., Methods: In this retrospective, single tertiary-care center study, consecutive patients considered for ICD implantation who were referred for LVEF assessment by CMR were included. Right and left ventricular function and volumes were measured., Results: In total, 102 patients (age 62±14 years; 23% women) had a mean LVEF of 28±11% and RVEF of 44±12%. The left ventricular and right ventricular end diastolic volume index was 140±42 mL/m 2 and 81±27 mL/m 2 , respectively. Eighty-six (84%) patients had a LVEF <35%, and 63 (62%) patients had right ventricular systolic dysfunction. Although there was a significant and moderate correlation between LVEF and RVEF ( r =0.40, p <0.001), 32 of 86 patients (37%) with LVEF <35% had preserved RVEF, while 9 of 16 patients (56%) with LVEF ≥35% had right ventricular systolic dysfunction (Kappa=0.041)., Conclusions: Among patients being considered for an ICD, there is a positive but moderate correlation between LVEF and RVEF. A considerable proportion of patients who qualify for an ICD based on low LVEF have preserved RVEF, and vice versa.

Background: Test-retest reproducibility is of utmost importance in follow-up of right ventricular (RV) volumes and function; optimal slice orientation though is not yet known. We compared test-retest reproducibility and intra-/inter-observer variability of right ventricular (RV) volumes and function assessed with short-axis and transverse cardiovascular magnetic resonance (CMR)., Methods: Eighteen volunteers underwent cine CMR for RV assessment obtaining ventricular coverage in short-axis and transverse slice orientation. Additional 2D phase contrast flow imaging of the main pulmonary artery (MPA) was performed. After complete repositioning repeat acquisitions were performed. Data sets were contoured by two blinded observers. Statistical analysis included Student's t-test, Bland-Altman plots, intra-class correlation coefficient (ICC) and 2-way ANOVA, SEM and minimal detectable difference calculations., Results: Heart rates (65.0 ± 7.4 vs. 67.6 ± 9.9 bpm; P = 0.1) and MPA flow (89.8 ± 16.6 vs. 87.2 ± 14.9 mL; P = 0.1) did not differ between imaging sessions. EDV and ESV demonstrated an inter-study bias of 0.4 %[-9.5 %,10.3 %] and 2.1 %[-12.3 %,16.4 %] for short-axis and 1.1 %[-7.3 %,9.4 %] and 0.8 %[-16.0 %,17.6 %] for transverse orientation, respectively. There was no significant interaction between imaging orientation and interstudy reproducibility (p = 0.395-0.824), intra-observer variability (p = 0.726-0.862) or inter-observer variability (p = 0.447-0.706) by 2-way ANOVA. Inter-observer agreement by ICC was greater for short axis versus transverse orientation for all parameters (0.769-0.986 vs. 0.625-0.983, respectively). Minimal detectable differences for short axis and transverse orientations were 10.1 mL/11.5 mL for EDV, 8.3 mL/8.4 mL for ESV and 4.1 % vs. 4.7 % for EF, respectively., Conclusion: Short-axis and transverse orientation both provide reliable and reproducible measures for follow-up of RV volumes and global function. Therefore, additional transverse SSFP cine CMR may not necessarily be required if performed for the sole purpose of quantitative volumetric RV assessment.

Leishmania infantum (syn. chagasi) is the etiologic agent of visceral leishmaniasis in Argentina, and the phlebotomine fly Lutzomyia longipalpis is its main vector. The objective of this study was to evaluate the effectiveness of Dragon Max ® , an emulsifiable concentrate formulation containing the pyrethroid permethrin and the larvicide pyriproxyfen, for Lu. longipalpis control under field conditions. The work was conducted in the city of Posadas (Misiones province, Argentina). Comparisons were performed between treated and untreated peridomiciles with poultry, which met previously determined criteria for favoring the presence of Lu. longipalpis. Henhouses and their surrounding area were treated, with the formulation (100 mg of permethrin and 2 mg/m 2 of pyriproxyfen) applied using a hand pump sprayer. Untreated henhouses were used as controls. Phlebotomine abundance was monitored before treatment and then weekly, using Centers for Disease Control and Prevention light traps. Lutzomyia longipalpis was the only phlebotomine species captured. A male/female ratio of 2.5 was observed. The more chickens there were in the henhouses, the greater the number of phlebotomines captured. The treatment resulted in a significant decrease in the number of individuals, which persisted for at least 2 wk. This encouraging result provides a baseline for further studies evaluating the possibility of using Dragon Max as a tool for Lu. longipalpis control.

Background: Women with transposition of the great arteries (TGA) following atrial redirection surgery are at risk of pregnancy-associated arrhythmia and heart failure. The cardiovascular magnetic resonance imaging (CMR) characteristics of these women and the relationship of CMR findings to pregnancy outcomes have not been described., Methods: We included 17 women with atrial redirection surgery and CMR within 2 years of delivery., Results: All women were asymptomatic at baseline (New York Heart Association Class 1). CMR studies were completed pre-pregnancy in 3, antepartum/peripartum in 2, and postpartum in 12 women. Three women (3/17, 18%) experienced major cardiovascular events related to pregnancy: cardiac arrest (n = 1) and symptomatic atrial arrhythmia (n = 2). Median gestational age at delivery was 38 weeks (24-39 weeks) and birth weight was 2770 g (2195-3720 g). Complications were seen in 3 offspring (3/17, 18%): death (n = 1) and prematurity (n = 2). CMR characteristics included median right ventricular end diastolic volume 119 mL/m 2 (range 85-214 mL/m 2 ) and median right ventricular ejection fraction (RVEF) 37% (range 30-51%). All women with cardiovascular complications had an RVEF < 35% (range 32-34%). The association between RVEF < 35% and cardiovascular complications trended towards statistical significance (p = 0.05). No statistically significant differences in CMR measurements were found between those with and without neonatal complications., Conclusions: While the majority of women in this cohort had successful outcomes following pregnancy, important cardiovascular complications were seen in a significant minority, all of whom had an RVEF < 35%. The preliminary findings of our study provide impetus for a larger prospective study to evaluate the prognostic role of CMR in pregnant women with atrial redirection surgery.

Background: A critical source of variability in dynamic perfusion computed tomography (DPCT) is the arterial input function (AIF). However, the impact of the AIF location in lung DPCT has not been investigated yet. The purpose of this study is to determine whether the location of the AIF within the central pulmonary arteries influences the accuracy of lung DPCT maps., Methods: A total of 54 lung DPCT scans were performed in three pigs using different rates and volumes of iodinated contrast media. Pulmonary blood flow (PBF) perfusion maps were generated using first-pass kinetics in three different AIF locations: the main pulmonary trunk (PT), the right main (RM) and the left main (LM) pulmonary arteries. A total of 162 time density curves (TDCs) and corresponding PBF perfusion maps were generated. Linear regression and Spearman's rank correlation coefficient were used to compare the TDCs. PBF perfusion maps were compared quantitatively by taking twenty six regions of interest throughout the lung parenchyma. Analysis of variance (ANOVA) was used to compare the mean PBF values among the three AIF locations. Two chest radiologists performed qualitative assessment of the perfusion maps using a 3-point scale to determine regions of perfusion mismatch., Results: The linear regression of the TDCs from the RM and LM compared to the PT had a median (range) of 1.01 (0.98-1.03). The Spearman rank correlation between the TDCs was 0.88 (P<0.05). ANOVA analysis of the perfusion maps demonstrated no statistical difference (P>0.05). Qualitative comparison of the perfusion maps resulted in scores of 1 and 2, demonstrating either identical or comparable maps with no significant difference in perfusion defects between the different AIF locations., Conclusions: Accurate PBF perfusion maps can be generated with the AIF located either at the PT, RM or LM pulmonary arteries.

Background: Adults with single ventricle physiology palliated with a Fontan circulation experience high mortality due to circulatory failure. Renin-angiotensin-aldosterone system (RAAS) genotype contributes to adverse cardiovascular outcomes in acquired heart failure. This study evaluated associations between RAAS genotype, ventricular mass and function in a contemporary cohort of adults with a Fontan circulation., Methods: This single-center prospective study included adults (n=106) seen after the Fontan operation (mean age 27±9years). Patients were genotyped for 5 pro-hypertrophic RAAS gene polymorphisms. Serum BNP, ventricular mass and function, and clinical events were compared between those with ≥2 homozygous risk genotypes ("high-risk", n=31) versus those with ≤1 homozygous risk genotypes ("low risk", n=75)., Results: "High-risk" genotype was associated with diastolic dysfunction and higher serum BNP levels. There was no association between RAAS genotype and either ventricular mass or systolic function. During a mean follow-up duration of 9.5±7.6years, late Fontan failure occurred in 20% (n=21) of patients, including 7 deaths. Serum BNP emerged as an independent predictor of late Fontan failure (HR 1.11 [CI 1.01-1.23] for each 50unit increase in BNP, p=0.04) and death alone (HR 1.25 [CI 1.07-1.47] for each 50unit increase in BNP, p=0.006). RAAS genotype was not associated with adverse clinical events., Conclusions: Fontan failure is common among adults with single ventricle physiology. RAAS genotype is not associated with increased ventricular mass but does appear to influence diastolic function late after the Fontan operation. Elevated BNP is an independent predictor of Fontan failure and mortality in adulthood., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)