Focal Scarring Research Articles

Discovery of a new long COVID mouse model via systemic histopathological comparison of SARS-CoV-2 intranasal and inhalation infection

Intranasal infection is commonly used to establish a SARS-CoV-2 mouse model due to its non-invasive procedures and a minimal effect from the operation itself. However, mice intranasally infected with SARS-CoV-2 have a high mortality rate, which limits the utility of this model for exploring therapeutic strategies and the sequelae of non-fatal COVID-19 cases. To resolve these limitations, an aerosolised viral administration method has been suggested. However, an in-depth pathological analysis comparing the two models is lacking. Here, we show that inhalation and intranasal SARS-CoV-2 (106 PFU) infection models established in K18-hACE2 mice develop unique pathological features in both the respiratory and central nervous systems, which could be directly attributed to the infection method. While the inhalation-infection model exhibited relatively milder pathological parameters, it closely mimicked the prevalent chest CT pattern observed in COVID-19 patients with focal, peripheral lesions and fibrotic scarring in the recuperating lung. We also found the evidence of direct neuron-invasion from the olfactory receptor neurons to the olfactory bulb in the intranasal model and showed the trigeminal nerve as an alternative route of transmission to the brain in inhalation infected mice. Even after viral clearance confirmed at 14 days post-infection, mild lesions were still found in the brain of inhalation-infected mice. These findings suggest that the inhalation-infection model has advantages over the intranasal-infection model in closely mimicking the pathological features of non-fatal symptoms of COVID-19, demonstrating its potential to study the sequelae and possible interventions for long COVID.

Biomarkers in transposition of the great arteries after arterial switch operation: A pilot trial with deep phenotyping

IntroductionTransposition of the great arteries (TGA) is a cyanotic congenital heart defect for which the arterial switch operation (ASO) is the preferred surgical repair. This study wanted to investigate whether a panel of biomarkers could identify morphologic as well as hemodynamic changes obtained by cardiac magnetic resonance (CMR). MethodsForty-four adult patients were included. Blood samples were collected to measure a broad range of biomarkers (galectin-3, ST2, GDF-15, PINP, ICTP, PIIINP, IGF-1, NT-proBNP, and hs-Tn). CMR was performed at rest and during exercise to assess cardiac function and morphology. Explorative statistics were performed between biomarker levels and CMR findings. ResultsAll patients were asymptomatic. While galectin-3, GDF-15, and NT-proBNP levels were within normal ranges, increased ST2, PINP, PIIINP, and ICTP levels were found in 20.5%, 34.1%, 45.5%, and 27.3% of patients, respectively. Moreover, 3 and 2 patients, respectively, showed elevated IGF-1 and hs-Tn levels. Although the ejection fraction of both ventricles was within normal limits, impaired cardiac reserve was found in 20 and 25% of patients for left and right ventricle, respectively. CMR revealed no evidence of diffuse interstitial fibrosis, while 4 patients showed focal ischemic scarring. However, no significant associations between serum biomarkers and CMR data could be detected. ConclusionThe results suggest that in asymptomatic ASO-repaired TGA patients serum level biomarkers are elevated and that this increase is not associated with morphological changes nor with a decreased cardiac reserve. Further study with larger sample sizes is required to draw conclusions with greater confidence.

Long-term cardiotoxicity in germ cell cancer survivors after platinum-based chemotherapy: cardiac MR shows impaired systolic function and tissue alterations

ObjectivesLong-term toxicities of germ cell cancer (GCC) treatment are of particular importance in young men with a life expectancy of several decades after curative treatment. This study aimed to investigate the long-term effects of platinum-based chemotherapy on cardiac function and myocardial tissue in GCC survivors by cardiac magnetic resonance (CMR) imaging.MethodsAsymptomatic GCC survivors ≥ 3 years after platinum-based chemotherapy and age-matched healthy controls underwent CMR assessment, including left ventricular (LV) and right ventricular (RV) ejection fraction (EF), strain analysis, late gadolinium enhancement (LGE) imaging, and T1/T2 mapping.ResultsForty-four survivors (age 44 [interquartile range, IQR 37–52] years; follow-up time 10 [IQR 5–15] years after chemotherapy) and 21 controls were evaluated. LV- and RVEF were lower in GCC survivors compared to controls (LVEF 56 ± 5% vs. 59 ± 5%, p = 0.017; RVEF 50 ± 7% vs. 55 ± 7%, p = 0.008). Seven percent (3/44) of survivors showed reduced LVEF (< 50%), and 41% (18/44) showed borderline LVEF (50–54%). The strain analysis revealed significantly reduced deformation compared to controls (LV global longitudinal strain [GLS] -13 ± 2% vs. -15 ± 1%, p < 0.001; RV GLS -15 ± 4% vs. -19 ± 4%, p = 0.005). Tissue characterization revealed focal myocardial fibrosis in 9 survivors (20%) and lower myocardial native T1 times in survivors compared to controls (1202 ± 25 ms vs. 1226 ± 37 ms, p = 0.016). Attenuated LVEF was observed after two cycles of platinum-based chemotherapy (54 ± 5% vs. 62 ± 5%, p < 0.001).ConclusionBased on CMR evaluation, combination chemotherapy with cumulative cisplatin ≥ 200 mg/m2 is associated with attenuated biventricular systolic function and myocardial tissue alterations in asymptomatic long-term GCC survivors.Clinical relevance statementPlatinum-based chemotherapy is associated with decreased systolic function, non-ischemic focal myocardial scar, and decreased T1 times in asymptomatic long-term germ cell cancer survivors. Clinicians should be particularly aware of the risk of cardiac toxicity after platinum-based chemotherapy.Key Points• Platinum-based chemotherapy is associated with attenuation of biventricular systolic function, lower myocardial T1 relaxation times, and non-ischemic late gadolinium enhancement.• Decreased systolic function and non-ischemic late gadolinium enhancement are associated with a cumulative cisplatin dose of ≥ 200 mg/m2.• Cardiac MRI can help to identify chemotherapy-associated changes in cardiac function and tissue in asymptomatic long-term germ cell cancer survivors.Graphical

Cardiac troponin T and I are differentially associated with myocardial fibrosis assessed by cardiac magnetic resonance imaging

Abstract Background Cardiac troponin T (cTnT) is more potently associated with non-cardiovascular (CV) mortality and cardiac troponin I (cTnI) is more specific for CV risk in the general population. Cardiovascular magnetic resonance imaging (CMR) measurement of extracellular volume (ECV) allows for assessment of diffuse myocardial fibrosis and is associated with adverse CV events. Focal myocardial scars are assessed by late gadolinium enhancement (LGE) and LGE scar presence is associated with unfavorable CV outcomes. The distinct clinical outcomes associated with cTnT and cTnI may be due to different subtypes and burden of myocardial fibrosis. Elevation of cTnT associates with increased ECV in a CMR referral base and with nonischemic myocardial scars in the general population. There is limited data comparing the associations of cTnT and cTnI with CMR indices of fibrosis in the general population. Purpose Perform head-to-head comparison of the associations of cTnT (Roche Elecsys) and cTnI (Abbott Alinity) with diffuse and focal myocardial fibrosis assessed by CMR. Methods Two hundred community-dwellers born in 1950 with approximately similar sex distribution were recruited. All participants were without contraindications to contrast-enhanced CMR, had normal kidney function and no known coronary artery disease. For the study a 1.5-T Philips MRI clinical scanner was used. Diffuse fibrosis was estimated by septal ECV and focal scars were quantified by LGE and classified as either ischemic or nonischemic. Complete MOLLI-sequence for assessment of ECV was present in 192 participants and 198 participants had complete LGE sequence. Logistic regression analysis was used to examine relationships between log transformed cardiac troponins and CMR indices of myocardial fibrosis, adjusting for a priori selected established cardiovascular risk factors. We analyzed ECV according to cut-off values based on the upper sex-specific quartile. Results The median age was 69 (68.6-69.3) and 52% were male (Table 1). The upper sex-specific quartile of ECV was 27% for men and 28% for women. cTnT was associated with ECV in the fully adjusted model (odds ratio [OR] 1.98, 95% CI 1.08-3.64), in contrast to cTnI which was not associated with ECV in any of the models (Table 2). cTnT (OR 3.71 95% CI 1.83-7.50) and cTnI (OR 1.69 95% CI 1.24-2.30) were associated with the presence of any LGE scar in the fully adjusted model, but the association was stronger for cTnT (p for comparison = 0.024). cTnT and cTnI were significantly associated with nonischemic scars in all models (Table 2), but stronger for cTnT (p for comparison = 0.018). In the fully adjusted model only cTnI was associated with the presence of ischemic scars (OR 1.66 95% CI 1.05-2.61). Conclusion(s) In our cohort of community-dwellers, cTnT is the stronger marker of diffuse and nonischemic myocardial fibrosis, while cTnI seems to more strongly reflect the presence of ischemic scar as assessed by CMR.Participant characteristicsAssociations of cTnT and cTnI

Association between left ventricular strain and fibrosis in severe aortic regurgitation with preserved ejection fraction: a magnetic resonance and histology study

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Institutional Grant Na Homolce Hospital Background The presence and extent of myocardial fibrosis are associated with poor outcomes in patients with severe aortic regurgitation. In the present study, we tested a correlation between left ventricular (LV) strain derived by using feature-tracking cardiac magnetic resonance (MRI) and diffuse myocardial fibrosis percentage (DMF%) at quantitative histology. Methods A study population included 23 patients (age 51 ± 12 years, 78% males) who underwent perioperative myocardial biopsy during aortic valve surgery for severe aortic regurgitation and who had a satisfactory pre-surgery MRI. Myocardial specimens obtained with a deep needle technique from the basal interventricular septum were stained with picrosirius red, digitalized, and analyzed using Image J software by a pathologist blinded to imaging findings. The DMF% was calculated as a ratio of the total collagen content to the total area. MRI-derived global longitudinal-(GLS), circumferential- (GCS), and radial (GRS) strain, as well as their ratio to heart rate and systolic blood pressure, were assessed using a feature-tracking technique by a certified imager blinded to histological analysis. Results Compared to normal values, all patients showed increased DMF% (19 ± 9%) and decreased GLS (15 ± 2%) despite preserved LV ejection fraction (64 ± 7%). Out of all the imaging parameters, only GLS/heart rate ratio, GCS/heart rate ratio and extracellular volume fraction showed a significant correlation with DMF% (Table 1, Figure 1). In contrast, GLS and GCS only tended to correlate with DMF%. The remaining parameters including GRS did not show a significant association. Patients with focal midwall scar in late gadolinium enhancement imaging (n=8, 35%), which was mainly localized in the basal septum, had similar GLS as than patients without focal scar (14.5±2.3 vs 15.3±2.3, p = 0.768). Conclusions Feature-tracking-derived ratios of LV GLS and GCS over heart rate are the most promising indices for non-invasive assessment of diffuse myocardial fibrosis in severe aortic regurgitation with preserved ejection fraction. Figure 1 Legend Correlation of a GLS/HR ratio 1A) and GLS 1B) with diffuse myocardial fibrosis %. Myocardial histology stained with Picrosirius red (collagen fibers are in red).

Cardiac troponin T, NT-proBNP and GDF-15 associate with future focal myocardial scar types, but not diffuse fibrosis assessed by cardiac magnetic resonance

Abstract Funding Acknowledgements Type of funding sources: Other. Main funding source(s): Akershus University Hospital Trust, Vestre Viken Hospital Trust, South-Eastern Norway Regional Health Authority, Roche Diagnostics provided reagents for hs-cTnT analyses Background In cardiovascular risk prediction, there is growing evidence that imaging and circulating cardiac biomarkers provide incremental prognostic value compared to single biomarkers or traditional risk factors. In patients with suspected or established cardiovascular disease (CVD), cardiac troponin T (cTnT) and N-terminal pro B-type natriuretic peptide (NT-proBNP) associate with focal and diffuse fibrosis assessed by cardiac magnetic resonance (CMR) imaging. There is limited data on the associations between established and emerging circulating cardiac biomarkers with subsequent myocardial fibrosis in subjects without CVD recruited from the general population. Purpose Assess the associations between biomarkers of cardiac injury (cTnT), stress (NT-proBNP) and fibrosis and inflammation (growth differentiation factor-15, GDF-15), and subsequent focal and diffuse myocardial fibrosis assessed by CMR imaging. Methods We recruited 200 study participants born in 1950 from the general population. All participants were without known coronary artery disease or renal dysfunction. cTnT, NT-proBNP, and GDF-15 were measured in samples collected at baseline in 2012–2015, and CMR was performed 4–7 years later. Presence and type (ischemic/non-ischemic) of focal myocardial fibrosis were assessed by late gadolinium enhancement (LGE) imaging. Diffuse fibrosis was assessed by the extracellular volume (ECV) in the midventricular septum. Logistic regression analysis was used to examine relationships between log transformed concentrations of cardiac biomarkers and CMR parameters. Results The median age was 63.9 (63.4–64.5) and 52% were male (Table 1). cTnT was associated with presence of any LGE scar adjusted for common cardiovascular risk factors (OR 1.85, 95% CI 1.25–2.72), but this association was attenuated when left ventricular mass was added to the model (Table 2). NT-proBNP (OR 1.66, 95% CI 1.10–2.72) and GDF-15 (OR 4.45, 95% CI 1.29–15.27) were associated with presence of any LGE scar in the fully adjusted models (Table 2). cTnT (OR 1.90, 95% CI 1.06–3.39) and NT-proBNP (OR 2.72, 95% CI 1.29–5.76) were associated with ischemic scars. Only GDF-15 (OR 4.52, 95% CI 1.09–18.72) associated with non-ischemic scars in adjusted models. None of the biomarkers were significantly associated with ECV. Conclusion(s) In a general population cohort, biomarkers of myocardial injury and stress associate with ischemic type scars, but not diffuse fibrosis. GDF-15, an emerging circulating biomarker of fibrosis and inflammation, associates with non-ischemic type scars.

Diffuse Myocardial Fibrosis on Cardiac Magnetic Resonance Imaging Is Related to Galectin-3 and Predicts Outcome in Heart Failure.

Ongoing adverse remodeling is a hallmark of heart failure (HF), which might be reflected by either focal or diffuse myocardial fibrosis. Therefore, in (pre)clinical settings, we used immunohistochemistry or cardiac magnetic resonance imaging (CMR) to investigate the association of (focal or diffuse) fibrosis with cardiac biomarkers and adverse events in HF. In C57Bl/6J mice, we determined the presence and extent of myocardial fibrosis 6 weeks post-myocardial infarction (MI). Furthermore, we studied 159 outpatient HF patients who underwent CMR, and determined focal and diffuse fibrosis by late gadolinium enhancement (LGE) and post-contrast T1 time of the non-LGE myocardium, respectively. HF patients were categorized based on the presence of LGE, and by the median post-contrast T1 time. Kaplan-Meier and Cox regression analyses were used to determine the association of fibrosis with HF hospitalization and all-cause mortality. LGE was detected in 61 (38%) patients. Cardiac biomarker levels were comparable between LGE-positive and LGE-negative patients. LGE-positive patients with a short T1 time had elevated levels of both NT-proBNP and galectin-3 (1611 vs. 453 ng/L, p = 0.026 and 20 vs. 15 μg/L, p = 0.004, respectively). This was not observed in LGE-negative patients. Furthermore, a short T1 time in LGE-positive patients was associated with a higher risk of adverse events (log-rank p = 0.01). This study implies that cardiac biomarkers reflect active remodeling of the non-infarcted myocardium of patients with focal myocardial scarring. Diffuse fibrosis, in contrast to focal scarring, might have a higher prognostic value regarding adverse outcomes in HF patients.

Skin-Fat Composite Grafts for Reconstructing Large Full-Thickness Skin Defects.

The uppermost layer of subcutaneous tissue has a rich vascular network, the subdermal plexus and multiple perforating vessels in the interlobular septa. When skin-fat composite grafts (SFCGs) include this uppermost layer, they can be readily vascularized to enhance survival. The authors describe their clinical experience with large SFCG transplantations. This retrospective study included patients who underwent SFCG transplantation for large, full-thickness skin defects, formed after burn scar contracture or contraction deformity excision. The recipient tissue bed was prepared by retaining the deepest layer of scar tissue or reticular dermis to preserve the interlobular septa, subdermal plexus, and ascending arterioles above the subcutaneous tissue. The SFCG was prepared by trimming fat lobules and preserving the interlobular septa and vessels to form a 1- to 4-mm-thick base of subdermal fat tissue. The trimmed SFCG was placed onto the defective tissue and secured with a tie-over dressing. Among 86 grafts, 76 (88.4%) survived completely (sizes, 6 to 161 cm 2 ; mean surface area, 68.7cm 2 ). Focal skin sloughing or graft loss occurred in 10 cases. These events were followed by spontaneous healing in eight cases. Focal hypertrophic scars formed in six cases. In 15 cases, hyperpigmentation occurred, but improved gradually. Most transplantations achieved satisfactory pliability (93.0%), contour (90.7%), and color (88.4%). SFCGs survived better than expected with minimal complications, probably because of the preservation of rich vascular networks in both the recipient and SFCG tissues. Therefore, SFCG transplantation may be a good option for reconstructing full-thickness skin defects with a large surface area. Therapeutic, IV.

CMR feature tracking in patients with dilated cardiomyopathy: patterns of myocardial strain and focal fibrosis

BackgroundThere is a paucity of data on cardiovascular magnetic resonance feature tracking (CMR-FT) in patients with dilated cardiomyopathy (DCM). We aimed at describing global and segmental myocardial strain patterns and...

Magnetic Resonance Imaging Synovial Classification Is Associated With Revision Indication and Polyethylene Insert Damage.

Patients with total knee arthroplasty (TKA) stiffness are commonly presumed to have arthrofibrosis though no specific test exists. In patients undergoing revision TKA, we asked the following question: (1) Do patients who are revised for stiffness display a synovial reaction on MRI that is different than patients revised for other reasons? (2) Do these patients have a different magnitude of polyethylene insert damage than patients revised for other reasons? and (3) Is the MRI synovial classification associated with polyethylene insert damage? Patients undergoing revision TKA for stiffness had a preoperative MRI performed, and the synovium was classified on MRI in a blinded fashion as arthrofibrosis, focal scarring, polymeric reaction, infection, or abnormal. At surgery, the polyethylene inserts were removed, and graded by 2 reviewers for total surface damage. Revision indication and MRI synovial classification were associated (P < .0001), with a greater proportion of patients assigned an MRI classification of arthrofibrosis revised for arthrofibrosis and a greater proportion of patients assigned a polymeric classification revised for aseptic loosening. Patients assigned an MRI synovial classification of polymeric had the greatest damage to the tibial insert (P < .0001), and patients revised for the clinical indication of aseptic loosening had the greatest damage to the tibial insert (P < .0001). Synovial grading on MRI is strongly associated with revision indication and polyethylene insert damage. In patients with stiffness in the absence of another complication, MRI can be a helpful diagnostic adjuvant in confirming the diagnosis of stiffness.

Radiologic features of immune checkpoint inhibitor-related nephritis with clinical correlation in biopsy-proven cases.

e14585 Background: Radiologic findings associated with biopsy proven immune checkpoint inhibitor (ICI) related nephritis have not been described. The objective of this study is to describe the radiologic features of immunotherapy related nephritis on computerized tomography (CT) and positron emission tomography (PET). A secondary objective is to investigate the association of these radiologic features with renal outcomes. Methods: A retrospective review of all biopsy proven ICI-related nephritis between February 2017 and April 2021 was performed and 34 patients were identified. CT and PET-CT scans before the initiation of immune checkpoint inhibitors (baseline), at nephritis and after resolution of nephritis were reviewed. Total kidney volume, renal parenchymal SUVmax, renal pelvis SUVmax and blood pool SUVmean were obtained. Results: The total kidney volume was significantly higher at nephritis compared to baseline (464.7±96.8 mL vs. 371.7±187.7 mL; p &lt; 0.001). Fifteen patients (44.1%) had &gt; 30% increase in total kidney volume at nephritis. A &gt; 30% increase in total kidney volume was associated with significantly higher renal toxicity grade (p = 0.007), higher peak creatinine level (p = 0.004) and more aggressive medical treatment (p = 0.011). New/increasing perinephric fat stranding was noted in 10 patients (29.4%) at nephritis. Among 8 patients with contrast-enhanced CT at nephritis, 1 patient (12.5%) developed bilateral wedge-shaped hypoenhancing cortical lesions that healed with focal scarring on subsequent scans. On PET-CT, the renal parenchymal SUVmax-to-blood pool SUVmean ratio was significantly higher at nephritis compared to baseline (2.13 vs. 1.68; p = 0.035). The renal pelvis SUVmax-to-blood pool SUVmean ratio was significantly lower at nephritis compered to baseline (3.47 vs. 8.22; p = 0.011). Conclusions: Bilateral increase in kidney size, new/increasing perinephric stranding and bilateral wedge-shaped hypoenhancing cortical lesions can occur in immunotherapy-related nephritis. On PET-CT, diffuse bilateral increase in radiotracer uptake throughout the renal cortex and decrease in radiotracer activity in the renal pelvis can be seen. A &gt; 30% increase in total kidney volume was associated with significantly higher renal toxicity grade and more aggressive medical treatment in a subset of patients. Acknowledgment: National Institute of Health K01 Award (N.A.: K01AI163412).

Short-coupled ventricular ectopics leading to cardiac arrest in a young woman

BackgroundThis case report highlights the importance of recognizing that ventricular ectopy may be a cause for syncope and sudden cardiac death, through triggered disorganized arrhythmia. In the context of syncope, ventricular ectopy should be carefully assessed for coupling interval and morphology.Case presentationA 39-year-old woman, who had presented with recurrent syncope, had a cardiac arrest shortly after admission that required emergency defibrillation. Review of her cardiac monitoring revealed an episode of polymorphic ventricular tachycardia which had degenerated into ventricular fibrillation. The dysrhythmia had been initiated by a short-coupled (R-on-T) ventricular ectopic (VE) beat. Anti-arrhythmic therapy was initiated in the form of hydroquinidine, but the patient continued to have frequent VEs of right bundle branch block (RBBB) morphology with a relatively narrow QRS complex and a variation in frontal axis. A cardiac MRI revealed late gadolinium enhancement of the posterior papillary muscle (indicative of focal scarring). The patient underwent electrophysiological mapping and catheter ablation of her ectopy. The patient made a good recovery and was discharged from hospital with a secondary prevention implantable cardioverter-defibrillator (ICD) in situ.ConclusionsShort-couped VEs that are superimposed onto the preceding T wave (R-on-T) are indicative of electrical instability of the heart and should prompt urgent investigation. By studying the morphologies and axes of the QRS complexes produced by VEs, we can identify their likely origins and ascertain their clinical significance.

Association of Myocardial Fibrosis and Stroke Volume by Cardiovascular Magnetic Resonance in Patients With Severe Aortic Stenosis With Outcome After Valve Replacement

Low-flow severe aortic stenosis (AS) has higher mortality than severe AS with normal flow. The conventional definition of low-flow AS is an indexed stroke volume (SVi) by echocardiography less than 35 mL/m2. Cardiovascular magnetic resonance (CMR) is the reference standard for quantifying left ventricular volumes and function from which SVi by CMR can be derived. To determine the association of left ventricular SVi by CMR with myocardial remodeling and survival among patients with severe AS after valve replacement. This multicenter longitudinal cohort study was conducted between January 2003 and May 2015 across 6 UK cardiothoracic centers. Patients with severe AS listed for either surgical aortic valve replacement (SAVR) or transcatheter aortic valve replacement (TAVR) were included. Patients underwent preprocedural echocardiography and CMR. Patients were stratified by echocardiography-derived aortic valve mean and/or peak gradient and SVi by CMR into 4 AS endotypes: low-flow, low-gradient AS; low-flow, high-gradient AS; normal-flow, low-gradient AS; and normal-flow, high-gradient AS. Patients were observed for a median of 3.6 years. Data were analyzed from September to November 2021. SAVR or TAVR. All-cause and cardiovascular (CV) mortality after aortic valve intervention. Of 674 included patients, 425 (63.1%) were male, and the median (IQR) age was 75 (66-80) years. The median (IQR) aortic valve area index was 0.4 (0.3-0.4) cm2/m2. Patients with low-flow AS endotypes (low gradient and high gradient) had lower left ventricular ejection fraction, mass, and wall thickness and increased all-cause and CV mortality than patients with normal-flow AS (all-cause mortality: hazard ratio [HR], 2.08; 95% CI, 1.37-3.14; P < .001; CV mortality: HR, 3.06; 95% CI, 1.79-5.25; P < .001). CV mortality was independently associated with lower SVi (HR, 1.64; 95% CI, 1.08-2.50; P = .04), age (HR, 2.54; 95% CI, 1.29-5.01; P = .001), and higher quantity of late gadolinium enhancement (HR, 2.93; 95% CI, 1.68-5.09; P < .001). CV mortality hazard increased more rapidly in those with an SVI less than 45 mL/m2. SVi by CMR was independently associated with age, atrial fibrillation, focal scar (by late gadolinium enhancement), and parameters of cardiac remodeling (left ventricular mass and left atrial volume). In this cohort study, SVi by CMR was associated with CV mortality after aortic valve replacement, independent of age, focal scar, and ejection fraction. The unique capability of CMR to quantify myocardial scar, combined with other prognostically important imaging biomarkers, such as SVi by CMR, may enable comprehensive stratification of postoperative risk in patients with severe symptomatic AS.

WITHDRAWN: Sudden death of an athlete due to concealed arrhythmogenic cardiomyopathy: Why preparticipation screening did fail

We report the case of a professional soccer athlete who died suddenly for arrhythmogenic cardiomyopathy that was not diagnosed at the time of preparticipation screening. Exercise testing had repeatedly shown effort-induced premature ventricular beats with normal echocardiography, which was considered reassuring. However, there is emerging evidence that cardiac diseases characterized by focal ventricular scarring may not cause wall motion abnormalities and can be revealed only by tissue characterization with cardiac magnetic resonance. Modern interpretation of premature ventricular beats features is essential to select athletes who should undergo advanced cardiac imaging investigations, to achieve a correct diagnosis and allow safe sport participation.

Risk factors for renal scarring and clinical morbidity in children with high-grade and low-grade primary vesicoureteral reflux

Primary vesicoureteral reflux (VUR) is associated with urinary tract infections (UTIs) and renal damage. However, the importance of early diagnosis of VUR has been questioned. Moreover, most studies have few patients with high-grade VUR. Hence, we retrospectively analyzed a large cohort of patients with primary high-grade and low-grade VUR and assessed risk factors for renal damage and clinical morbidity. We included patients (<18 years) at diagnosis with low-grade (1-3) or high-grade (4-5) primary VUR and noted their clinical history and presence of hypertension, low eGFR (<60ml/in/1.73m2), renal scarring (focal or generalised) and reduced differential renal function (DRF; <45%). Risk factors were assessed (in patients and renal units) by logistic regression and generalised estimating equation. Of 399 primary VUR patients, 255 (64%) had high-grade VUR. Indications for voiding cystourethrogram were recurrent UTI (38%), first UTI (28%) and antenatal hydronephrosis (17%). At diagnosis, 252 (65%) had renal scars (focal in 170 [44%], generalised in 82 [21%]), and 188 (47%) had reduced DRF. High-grade VUR patients were more likely than low-grade VUR patients to have renal scarring (75% vs. 49%, p<0.01), low eGFR (23% vs. 13%, p=0.04) and significant hypertension (26% vs. 13%, p=0.02). High-grade VUR was associated with generalised scars (odds ratio [OR] 11, p<0.001), focal scars (OR 3.1, p<0.001) and reduced DRF (OR 2.3, p<0.001) shown in the table. Male sex was a risk factor for generalised scars (OR 2.3, p=0.005). Focal scars were associated with recurrent UTIs (OR=1.8, p=0.004) and reduced DRF (OR 1.4, p=0.027). Patients with multiple focal scars were diagnosed at an older age (2 years [1,4] than those with single scars (1.5 years [1,4] or no scars (1 year [0, 3]), p=0.04). The prevalence of renal damage and clinical morbidity at VUR diagnosis was higher than other studies. High-grade VUR patients had a greater prevalence of renal damage, low eGFR and hypertension than low-grade VUR patients and was a risk factor for focal scars, generalised scars and reduced DRF. Focal scars were independently associated with recurrent UTI. Those with multiple scars were diagnosed later than those with single scars or no scars. High-grade VUR was associated with renal damage and clinical morbidity. Our study highlights the importance of diagnosing VUR early to identify patients who may warrant long-term follow-up and intervention to minimize morbidity.

Photodynamic Therapy in the Treatment of Vulvar Lichen Sclerosus: A Systematic Review of the Literature.

Vulvar lichen sclerosus (VLS) is a chronic inflammatory disease involving the genital skin and mucous membrane. Patients exhibit focal atrophy and destructive scarring, with an increased risk of malignant transformation. Due to objective symptoms as well as subjective complaints, patients with VLS experience emotional distress, lowered mood, and sexual dysfunction, which is reflected in impaired health-related quality of life. Thus, the necessity of implementing appropriate therapy at the earliest possible stage of the disease in order to avoid serious complications is highlighted. We presented the systematic review of available literature, performed with MEDLINE, Cinahl, Central, Scopus, and Web of Science databases. We identified a total of twenty relevant studies which indicate that photodynamic therapy (PDT) is a valuable therapeutic modality in the treatment of VLS.

Collagen-Targeted Peptides for Molecular Imaging of Diffuse Cardiac Fibrosis.

BackgroundCardiac fibrosis is the excessive deposition of extracellular matrix in the heart, triggered by a cardiac insult, aging, genetics, or environmental factors. Molecular imaging of the cardiac extracellular matrix with targeted probes could improve diagnosis and treatment of heart disease. However, although this technology has been used to demonstrate focal scarring arising from myocardial infarction, its capacity to demonstrate extracellular matrix expansion and diffuse cardiac fibrosis has not been assessed.Methods and ResultsHere, we report the use of collagen‐targeted peptides labeled with near‐infrared fluorophores for the detection of diffuse cardiac fibrosis in the β2‐AR (β‐2‐adrenergic receptor) overexpressing mouse model and in ischemic human hearts. Two approaches were evaluated, the first based on a T peptide that binds matrix metalloproteinase‐2‐proteolyzed collagen IV, and the second on the cyclic peptide EP‐3533, which targets collagen I. The systemic and cardiac uptakes of both peptides (intravenously administered) were quantified ex vivo by near‐infrared imaging of whole organs, tissue sections, and heart lysates. The peptide accumulation profiles corresponded to an immunohistochemically‐validated increase in collagen types I and IV in hearts of transgenic mice versus littermate controls. The T peptide could encouragingly demonstrate both the intermediate (7 months old) and severe (11 months old) cardiomyopathic phenotypes. Co‐immunostainings of fluorescent peptides and collagens, as well as reduced collagen binding of a control peptide, confirmed the collagen specificity of the tracers. Qualitative analysis of heart samples from patients with ischemic cardiomyopathy compared with nondiseased donors supported the collagen‐enhancement capabilities of these peptides also in the clinical settings.ConclusionsTogether, these observations demonstrate the feasibility and translation potential of molecular imaging with collagen‐binding peptides for noninvasive imaging of diffuse cardiac fibrosis.

Bright-blood and dark-blood phase sensitive inversion recovery late gadolinium enhancement and T1 and T2 maps in a single free-breathing scan: an all-in-one approach

BackgroundQuantitative cardiovascular magnetic resonance (CMR) T1 and T2 mapping are used to detect diffuse disease such as myocardial fibrosis or edema. However, post gadolinium contrast mapping often lacks visual contrast needed for assessment of focal scar. On the other hand, late gadolinium enhancement (LGE) CMR which nulls the normal myocardium has excellent contrast between focal scar and normal myocardium but has poor ability to detect global disease. The objective of this work is to provide a calculated bright-blood (BB) and dark-blood (DB) LGE based on simultaneous acquisition of T1 and T2 maps, so that both diffuse and focal disease may be assessed within a single multi-parametric acquisition.MethodsThe prototype saturation recovery-based SASHA T1 mapping may be modified to jointly calculate T1 and T2 maps (known as multi-parametric SASHA) by acquiring additional saturation recovery (SR) images with both SR and T2 preparations. The synthetic BB phase sensitive inversion recovery (PSIR) LGE may be calculated from the post-contrast T1, and the DB PSIR LGE may be calculated from the post-contrast joint T1 and T2 maps. Multi-parametric SASHA maps were acquired free-breathing (45 heartbeats). Protocols were designed to use the same spatial resolution and achieve similar signal-to-noise ratio (SNR) as conventional motion corrected (MOCO) PSIR. The calculated BB and DB LGE were compared with separate free breathing (FB) BB and DB MOCO PSIR acquisitions requiring 16 and 32 heart beats, respectively. One slice with myocardial infarction (MI) was acquired with all protocols within 4 min.ResultsMultiparametric T1 and T2 maps and calculated BB and DB PSIR LGE images were acquired for patients with subendocardial chronic MI (n = 10), acute MI (n = 3), and myocarditis (n = 1). The contrast-to-noise (CNR) between scar (MI and myocarditis) and remote was 26.6 ± 7.7 and 20.2 ± 7.4 for BB and DB PSIR LGE, and 31.3 ± 10.6 and 21.8 ± 7.6 for calculated BB and DB PSIR LGE, respectively. The CNR between scar and the left ventricualr blood pool was 5.2 ± 6.5 and 29.7 ± 9.4 for conventional BB and DB PSIR LGE, and 6.5 ± 6.0 and 38.6 ± 11.6 for calculated BB and DB PSIR LGE, respectively.ConclusionsA single free-breathing acquisition using multi-parametric SASHA provides T1 and T2 maps and calculated BB and DB PSIR LGE images for comprehensive tissue characterization.

Dense bone islands in pediatric patients: a case series study

BackgroundDense Bone Islands (DBIs) are anatomic variants defined as radiopaque lesions consisting of hamartomatous cortical bone, often presenting as incidental radiographic findings. DBIs can also be known as idiopathic osteosclerosis, bone whorl, focal periapical osteopetrosis, bone scar and enostosis. We found a paucity of literature for management and reporting of this condition in children. For this reason, the authors describe sixteen cases of children and adolescents with dense bony islands and suggest a pathway for management.Case seriesCases presented to the RNENT and Eastman Dental Hospital or private practice, either as chance findings or for diagnosis and treatment planning of undiagnosed radiopaque areas. The individuals were aged between 10 and 17 years; 6 boys and 10 girls. All radiographic reports described DBIs. Diagnoses were confirmed by a Dental and Maxillofacial Radiology Consultant and advised no intervention. In some cases, monitoring was advised. Caution in orthodontic tooth movement was advised for five patients.ConclusionDBIs are common findings that seldom require treatment; however, caution should be exercised when undertaking orthodontic movement in the area of a DBI due to a potential risk of root resorption. Accurate identification and multidisciplinary management are of utmost importance.

Abstract 14919: Myocardial T 1 Mapping for Prediction of Left Ventricular Reverse Remodeling in Patients With Recent-onset Dilated Cardiomyopathy: a Comparison With Histological Tissue Characterization

Background: Accurate prediction of left ventricular reverse remodeling (LVRR) in dilated cardiomyopathy (DCM) remains challenging. The purpose of this study is to assess the potential of cardiovascular magnetic resonance (CMR) T 1 mapping to predict LVRR by histological confirmation. Methods: Twenty-one DCM patients (12 male, mean age 49 ± 13 years) underwent cine, late gadolinium enhancement (LGE) CMR, and triple-slice T 1 mapping using a modified Look-Locker inversion recovery sequence at 3T before receiving optimal medical therapy. LVRR was defined as an absolute increase in LV ejection fraction (LVEF) from ≥10% to a final value of &gt;35%, accompanied by a decrease in LV end-diastolic volume (LVEDV) ≧10% at midterm (mean time 18 months) CMR follow-up. Extra-cellular volume (ECV) was quantified from pre and post-contrast T 1 values of the blood and myocardium with hematocrit correction. Biopsy samples were used for quantification of collagen volume fraction (CVF). Results: LVRR was observed in 11 patients (52%). The mean native T 1 , ECV, and histological CVF were 1395 ± 49 ms, 0.33 ± 0.03, 0.13 ± 0.04, respectively. Native T 1 yielded comparable ability to ECV measurements for detecting histological CVF (r=0.49, 0.52, both p &lt;0.05). While 14 patients (67%) showed focal scar on LGE, there was no significant difference in histological CVF between patients with and without focal scarring (p=0.6). Native T 1, but not ECV and CVF, correlated well with absolute LVEF increase and relative percent decrease of LVEDV and LV end-systolic volume (r=-0.55, 0.55, 0.56, all p &lt;0.05). Native T 1 &lt;1400 ms provided 90% sensitivity and 82% specificity, with the C-statistic of 0.86 (95% CI 0.64-0.97), for predicting LVRR. On the other hand, the C-statistic of ECV, LGE and histological CVF were 0.72 (95% CI 0.48-0.89), 0.53 (95% CI 0.31-0.75) and 0.66 (95% CI 0.43-0.85), respectively. Conclusions: Myocardial native T 1 have the potential to predict LVRR beyond LGE and histological assessment.