Extracellular Volume Measurements Research Articles

Assessment of Myocardial Fibrosis in Marfan Syndrome Using Cardiac Magnetic Resonance Imaging.

Impaired myocardial function and arrhythmia are important manifestations of Marfan syndrome (MFS). Studies assessing myocardial fibrosis in relation to these manifestations are scarce. This cross-sectional, single-center study assessed ventricular volumes, ventricular function, and myocardial fibrosis by cardiac magnetic resonance imaging (CMR) in patients with MFS harboring a (likely) pathogenic FBN1 variant. The presence and extent of fibrosis were assessed by late gadolinium enhancement (LGE) and extracellular volume measurement (ECV). Data on 24-h Holter monitoring and clinical data were extracted from electronic patient records. The study included 32 unselected patients with MFS (median age 38 years [range 10-69], 41% women). No focal myocardial fibrosis was detected. Six patients (21%) had diffuse fibrosis (ECV > 29%). No association was found between the presence of diffuse fibrosis and clinically relevant myocardial dysfunction. Five patients (16%) had reduced left ventricular ejection fraction (LVEF < 55%). While all of these exhibited mitral annular disjunction (MAD), only two had ECV > 29%. Patients with MAD had increased indexed LV volumes (median end-diastolic volume, 92 mL/m2 [IQR, 78-100] vs. 78 mL/m2 [IQR, 71-87]; median end-systolic volume, 31 mL/m2 [IQR, 23-46] vs. 22 mL/m2 [IQR, 21-28]), also after adjusting for the presence of mitral and aortic valve regurgitation. No differences in ECV were seen between patients with and without MAD. In this cohort of patients with MFS, focal myocardial fibrosis was not detected using CMR. Although diffuse fibrosis was observed in 21% of patients, no evident connection to clinically relevant myocardial dysfunction was found. Further studies should evaluate the impact of diffuse fibrosis on clinical outcome prediction.

Comparative assessment of extracellular volume metrics in predicting adverse outcomes in patients with transthyretin amyloid cardiomyopathy

Abstract Introduction The indexed total extracellular volume of the myocardium (iECV) has recently been proposed to be superior in predicting adverse outcome in severe aortic stenosis as compared to conventional extracellular volume (ECV). So far, no study has assessed the comparative predictive performance of both measures in transthyretin amyloid cardiomyopathy (ATTR-CM). Aim We aimed to assess and compare the predictive performance of conventional ECV against iECV in determining adverse outcomes in patients with ATTR-CM. Methods From 2012 to 2023, patients with ATTR-CM undergoing contrast cardiac magnetic resonance (CMR) imaging prior to any specific treatment were enrolled. Both, conventional ECV and iECV were quantified on CMR alongside left ventricular volumetrics and late gadolinium enhancement. Adverse outcome was defined as a composite endpoint of hospitalization for heart failure and/or death. Results Analysis of 178 patients with ATTR-CM (82% males, mean age 77±8 years) revealed a mean conventional ECV of 47±13% and a mean iECV of 46±21 mL/m2, with a median follow-up of 2.5 years (IQR: 1.00-4.08 years). Conventional ECV was significantly associated with the composite endpoint (HR=1.03, 95%CI=1.01–1.05, p=0.006), outperforming iECV (HR=1.01, 95%CI=1.00–1.02, p=0.010). On multivariate analysis, adjusted for age, sex and left ventricular function, conventional ECV remained associated with the composite endpoint (p=0.002), while iECV demonstrated a slightly less significant association (p=0.003). Kaplan-Meier analysis, stratified by conventional ECV tertiles, revealed that patients in the highest tertile (ECV ≥53%) demonstrated the highest event rate (p = 0.043 by log rank test, see Figure 1A), in contrast to iECV (p=NS, Figure 1B). Conclusions High conventional ECV, among CMR fibrosis markers, is linked to heart failure hospitalizations and death in ATTR-CM, demonstrating superior prognostic value compared to iECV. Conventional ECV measurements may offer enhanced risk stratification for patients with ATTR-CM.

Myocardial extracellular volume measurement using cardiac computed tomography.

Myocardial fibrosis is a common endpoint of many cardiac diseases and increasingly recognized as a predictor of heart failure, arrhythmia, and death. Recent studies have utilised cardiac computed tomography (CT) scans with delayed phase imaging to quantify diffuse fibrosis of the myocardium. CT extracellular volume (CT-ECV) measurement correlates well with CMR and histological myocardial fibrosis. Furthermore, CT-ECV predicts outcomes such as death, heart failure and arrhythmia in various disease states. This review summarizes the rationale and methodology behind CT-ECV measurement and provides a detailed summary of the current clinical evidence for the use of CT-ECV.

Photon-counting detector computed tomography in cardiac imaging.

Photon-counting detector computed tomography (PCD-CT) has emerged as arevolutionary technology in CT imaging. PCD-CT offers significant advancements over conventional energy-integrating detector CT, including increased spatial resolution, artefact reduction and inherent spectral imaging capabilities. In cardiac imaging, PCD-CT can offer amore accurate assessment of coronary artery disease, plaque characterisation and the in-stent lumen. Additionally, it might improve the visualisation of myocardial fibrosis through qualitative late enhancement imaging and quantitative extracellular volume measurements. The use of PCD-CT in cardiac imaging holds significant potential, positioning itself as avaluable modality that could serve as aone-stop-shop by integrating both angiography and tissue characterisation into asingle examination. Despite its potential, large-scale clinical trials, standardisation of protocols and cost-effectiveness considerations are required for its broader integration into clinical practice. This narrative review provides an overview of the current literature on PCD-CT regarding the possibilities and limitations of cardiac imaging.

Elevated myocardial extracellular volume fraction is associated with the development of conduction pathway defects following transcatheter aortic valve replacement.

Transcatheter aortic valve replacement (TAVR) has become an established method of aortic stenosis treatment but suffers from the risk of heart block and pacemaker requirement. Risk stratification for patients who may develop heart block remains imperfect. Simultaneously, myocardial fibrosis as measured by cardiac magnetic resonance imaging (CMR) has been demonstrated as a prognostic indicator of ventricular recovery and mortality following TAVR. However, the association of CMR-based measures of myocardial fibrosis with post-TAVR conduction disturbances has not yet been explored. We evaluated whether myocardial fibrosis, as measured by late gadolinium enhancement and extracellular volume (ECV) from CMR would be associated with new conduction abnormalities following TAVR. One hundred seventy patients who underwent CMR within 2 months before TAVR were retrospectively reviewed. Septal late gadolinium enhancement (LGE) and ECV measurements were made as surrogates for replacement and interstitial fibrosis respectively. New conduction abnormalities were defined by the presence of transient or permanent atrioventricular block, new bundle branch blocks, and need for permanent pacemaker. Association of myocardial fibrosis and new conduction derangements were tested using receiver operator curve (ROC) and regression analysis in patients with and without pre-existing conduction issues. Forty-six (27.1%) patients developed post-TAVR conduction deficits. ECV was significantly higher among patients who experienced new conduction defects (26.2 ± 3.45% vs. 24.7% ± 4.15%, p value: 0.020). A greater fraction of patients that had new conduction defects had an elevated ECV of ≥26% (54.3% vs. 36.3%, p value: 0.026). ECV ≥ 26% was independently associated with the development of new conduction defects (odds ratio [OR]: 2.364, p value: 0.030). ROC analysis revealed a significant association of ECV with new conduction defects with an area under the receiver operating characteristic curve (AUC) of 0.632 (95% confidence interval: 0.555-0.705, p value: 0.005). The combination of prior right bundle branch block (RBBB) and ECV revealed a greater AUC of 0.779 (0.709-0.839, p value: <0.001) than RBBB alone (Delong p value: 0.049). No association of LGE/ECV with new conduction defects was observed among patients with pre-existing conduction disease. Among patients without baseline conduction disease, ECV was independently associated with the development of new conduction deficits (OR: 3.685, p value: 0.008). The present study explored the association of myocardial fibrosis, as measured by LGE and ECV with conduction deficits post-TAVR. Our results demonstrate an association of ECV, and thereby interstitial myocardial fibrosis, with new conduction derangement post-TAVR and introduce ECV as a potentially new risk stratification tool to identify patients at higher risk for needing post-TAVR surveillance and/or permanent pacemaker.

Influence of cardiac cycle on myocardial extracellular volume fraction measurements with dual-layer computed tomography.

In cardiac computed tomography (CT), the best image quality is obtained at mid-diastole at low heart rates (HRs) and at end-systole at high HRs. On the other hand, extracellular volume (ECV) measurements may be influenced by the cardiac phase. Therefore, we aimed to clarify the influence of the cardiac phase on the image quality and ECV values obtained using dual-layer spectral computed tomography (DLCT). Fifty-five patients (68.0±14.5 years; 26 men) with cardiac diseases who underwent retrospective electrocardiogram-gated myocardial CT delayed enhancement (CTDE) between February 2019 to April 2022 were enrolled. The ECVs at the right ventricle (RV) and left ventricle (LV) walls in the end-systolic and mid-diastolic phases were calculated using iodine-density measurements from CTDE spectral data. Iodine-density image quality was classified on a 4-point scale. ECV and image quality across cardiac phases were compared using the t-test and Wilcoxon signed-rank test, respectively. Inter- and intraobserver variability were evaluated using intraclass correlation coefficient (ICC) values. The ECV of the septal regions during mid-diastole was significantly higher than that during end-systole. Other regions showed similar ECV measurements in both groups (P=0.13-0.97), except for the LV anterior wall and LV posterior wall at the base-ventricular level. The image-quality score in end-systole was significantly higher than that in mid-diastole (systole vs. diastole: 3.6±0.5 vs. 3.2±0.7; P=0.0195). Intra- and interobserver variabilities for RV ECV measurements at the end-systolic phase were superior to those at the mid-diastolic phase, whereas the corresponding values for LV ECV measurements were similar. Septal ECV showed small but significant differences while other region ECV showed no difference during the cardiac cycle. RV ECV measurements in the end-systolic phase were more reproducible than those in the mid-diastolic phase.

Imaging of Cardiac Fibrosis: An Update, From the AJR Special Series on Imaging of Fibrosis.

Myocardial fibrosis (MF) is defined as excessive production and deposition of extra-cellular matrix (ECM) proteins that result in pathologic myocardial remodeling. Three types of MF have been identified: replacement fibrosis from tissue necrosis, reactive fibrosis from myocardial stress, and infiltrative interstitial fibrosis from progressive deposition of nondegradable material such as amyloid. Although echocardiography, nuclear medicine, and CT play important roles in the assessment of MF, MRI is pivotal in the evaluation of MF, with the late gadolinium enhancement (LGE) technique used as a primary end point. The LGE technique focuses on the pattern and distribution of gadolinium accumulation in the myocardium and assists in the diagnosis and establishment of the cause of both ischemic and nonischemic cardiomyopathy. LGE MRI also aids prognostication and risk stratification. In addition, LGE MRI is used to guide the management of patients considered for ablation for arrhythmias. Parametric mapping techniques, including T1 mapping and extracellular volume measurement, allow detection and quantification of diffuse fibrosis, which may not be detected by LGE MRI. These techniques also allow monitoring of disease progression and therapy response. This review provides an update on the imaging of MF, including prognostication and risk stratification tools, electrophysiologic considerations, and disease monitoring.

#500 Monitoring relative blood volume and calf bioimpedance in hemodialysis patients

Abstract Background and Aims Measurements of relative blood volume (RBV, %) are used to monitor the relative change in blood plasm during hemodialysis (HD). Continuous measurement of calf extracellular volume (cECV) during HD allows the calculation of relative change in cECV (RCE). RCE was defined as the ratio of cECV to its initial value, cECV0 (RCE = 100 × cECV/cECV0, %). The aim of our study was to investigate the relationship between RBV, RCE and the occurrence of intradialytic hypotension (IDH). Method Fifty-five HD patients were studied. We reduced the HD target weight stepwise by 0.1 to 0.2 kg per HD session until clinically defined IDH symptoms occurred. RBV was monitored using the blood volume monitor (BVM, Fresenius Medical Care, Germany). Whole body bioimpedance spectroscopy (wBIS) provided whole body ECV (wECV) and intracellular volume (wICV) pre and post HD. Continuous calf bioimpedance (Hydra 4200, Xitron Technologies, San Diego, CA USA) provided cECV during HD. Pre HD overhydration (OH) was calculated according to whole body composition model (Chamney et al, Am J Clin Nutr 2007; 85:80). Total number of HD sessions in all patients were divided into three groups according to the pre HD OH: 1) normal OH (NOH, OH &amp;lt; 1 L), 2) moderate OH (MOH, 1 ≤ OH &amp;lt; 4 L) and 3) severe OH (SOH, OH ≥ 4 L). Furthermore, patients were stratified by the presence or absence of IDH in each hydration group. Ultrafiltration rate (UFR), pre HD body weight, body mass index (BMI) were measured. Minimal RBV (RBVMin) and minimal RCE (RCEMin) in each HD session were recorded. These measures represent maximum reduction of fluid in the intravascular and interstitial spaces, respectively. Reducing cECV can be considered as refilling fluid from interstitial transferring to intravascular space driving by ultrafiltration. The difference between RCEMin and RBVMin was defined as vascular refilling capacity. Linear mixed-effect logistic regression (LMELR) analysis was applied to explore relationships between IDH with RBVMin, RCEMin, wECV and BMI. Results We studied 621 HD sessions in 55 patients. MOH was present in 57%, SOH in 22% and NOH in 21% of total number of HD sessions respectively. There were significant differences in age, UFR, RBVMin, RCEMin, pre HD wECV, BMI between three groups, while the IDH rate did not differ significantly (Table 1). RBVMin was inversely correlated with UFR (Fig. 1) in all measurements. Pre HD wECV was the only factor associated with IDH in overall measurement. Pre HD wECV was significantly lower in IDH than in non-IDH patients in the NOH group (Fig. 2). In the MOH group, UFR and RCEMin-RBVMin were higher in IDH than in non-IDH patients (Fig. 3a and Fig. 3b). In the SOH group, Pre HD OH is the major factor associated with IDH (Fig. 4). Conclusion This study found that the major factors leading to IDH are 1) lower hydration status; 2) relative higher UFR; and 3) the limited refilling capacity. RBVMin correlated with UFR, but it did not predict IDH. Combined analysis of RBV and calf bioimpedance may provide a means to quantitate the fluid transport between intravascular and interstitial compartments and could add to an early IDH warning system.

Prognostic value of measurement of myocardial extracellular volume using dual-energy CT in heart failure with preserved ejection fraction

Diffuse myocardial fibrosis is associated with adverse outcomes in heart failure with preserved ejection fraction (HFpEF). Dual-energy CT (DECT) can noninvasively assess myocardial fibrosis by quantification of extracellular volume (ECV) fraction. This study evaluated the association between ECV measured by DECT and clinical outcomes in patients with HFpEF. 125 hospitalized HFpEF patients were enrolled in this retrospective cohort study. ECV was measured using DECT with late iodine enhancement. The composite endpoint was defined as HFpEF hospitalization and all-cause mortality during the follow-up. During the median follow-up of 10.4 months, 34 patients (27.20%) experienced the composite outcomes, including 5 deaths; and 29 HFpEF hospitalizations. The higher DECT-ECV group had higher rates of composite outcomes than the low ECV group (log-rank X2 = 6.818, P = 0.033). In multivariate Cox regression analysis, the ECV (HR 1.17, 95% CI 1.06–1.30, P = 0.001) and NT-pro BNP (HR 2.83, 95% CI 1.16–6.88, P = 0.022) were independent risk factors for the adverse outcomes. Myocardial ECV measured using DECT was an independent risk factor for adverse outcomes in patients with HFpEF.

Carbohydrate antigen 125: a useful marker of congestion, fibrosis, and prognosis in heart failure with preserved ejection fraction.

Heart failure (HF) with preserved ejection fraction (HFpEF) is a disease associated with high morbidity and mortality, for which it is difficult to identify patients with the poorest prognosis in routine clinical practice. Carbohydrate antigen 125 (CA 125) has been shown to be a potential marker of congestion and prognosis in HF. We sought to better characterize HFpEF patients with high CA 125 levels by using a multimodal approach. We prospectively enrolled 139 HFpEF patients (78±8years; 60% females) and 25 controls matched for age and sex (77±5years; 60% females). They underwent two-dimensional echocardiography, cardiac magnetic resonance with late gadolinium enhancement [including extracellular volume (ECV) measurement], and serum measurements of CA 125 level. The primary endpoint of the study was a composite of all-cause mortality or first HF hospitalization. The prognostic impact of CA 125 was determined using Cox proportional hazard models. Median CA 125 levels were significantly higher in HFpEF patients compared with controls [CA 125: 23.5 (14.5-44.7) vs. 14.6 (10.3-21.0) U/mL, P=0.004]. CA 125 levels were positively correlated with a congestion marker [N-terminal pro-brain natriuretic peptide (NT-proBNP) levels, Pearson's r=0.37, P<0.001] and markers of cardiac fibrosis estimated by both ECV (Pearson's r=0.26, P=0.003) and fibroblast growth factor 23 levels (Pearson's r=0.50, P<0.001). Over a median follow-up of 49 (22-64) months, 97 HFpEF patients reached the composite endpoint. Even after adjustment for the Meta-Analysis Global Group in Chronic risk score, a CA 125 level ≥35U/mL was still a significant predictor of the composite endpoint [hazard ratio (HR): 1.58 (1.04-2.41), P=0.032] and more particularly of HF hospitalization [HR: 1.81 (1.13-2.92), P=0.014]. In contrast, NT-proBNP levels were not an independent predictor. CA 125 levels were significantly higher in HFpEF patients compared with controls matched for age and sex and were associated with markers of congestion and cardiac fibrosis. CA 125 levels were a strong and independent predictor of HF hospitalization in HFpEF patients. These data suggest a potential value of CA 125 as a biomarker for staging and risk prediction in HFpEF.

ECMR 1-28 - T1 and Extracellular Volume Measurements. Normal Values at 0.55T and Validation in Comparison with 1.5T

ECMR 1-28 - T1 and Extracellular Volume Measurements. Normal Values at 0.55T and Validation in Comparison with 1.5T

Right ventricular fibrosis in adults with uncorrected secundum atrial septal defect and pulmonary hypertension: a cardiovascular magnetic resonance study with late gadolinium enhancement, native T1 and extracellular volume.

Right ventricular (RV) fibrosis represents both adaptive and maladaptive responses to the overloaded RV condition. Its role in pulmonary hypertension (PH) associated with secundum atrial septal defect (ASD), which is the most common adult congenital heart disease (CHD), remains poorly understood. We enrolled 65 participants aged ≥18 years old with uncorrected secundum ASD who had undergone clinically indicated right heart catheterization (RHC), divided into the non-PH group (n = 7), PH group (n = 42), and Eisenmenger syndrome (ES) group (n = 16). We conducted cardiovascular magnetic resonance (CMR) studies with late gadolinium enhancement (LGE) imaging, native T1 mapping, and extracellular volume (ECV) measurement to evaluate the extent and clinical correlates of RV fibrosis. LGE was present in 94% of the population and 86% of the non-PH group, mostly located at the right ventricular insertion point (RVIP) regions. LGE in the septal and inferior RV region was predominantly observed in the ES group compared to the other groups (p = 0.031 and p < 0.001, respectively). The mean LGE scores in the ES and PH groups were significantly higher than those in the non-PH group (3.38 ± 0.96 vs. 2.74 ± 1.04 vs. 1.57 ± 0.79; p = 0.001). The ES and PH groups had significantly higher degrees of interstitial RV fibrosis compared to those in the non-PH group, indicated by native T1 (1,199.9 ± 68.9 ms vs. 1,131.4 ± 47.8 ms vs. 1,105.4 ± 44.0 ms; p < 0.001) and ECV (43.6 ± 6.6% vs. 39.5 ± 4.9% vs. 39.4 ± 5.8%; p = 0.037). Additionally, native T1 significantly correlated with pulmonary vascular resistance (r = 0.708, p < 0.001), RV ejection fraction (r = -0.468, p < 0.001) and peripheral oxygen saturation (r = -0.410, p = 0.001). In patients with uncorrected secundum ASD, RV fibrosis may occur before the development of PH and progressively intensify alongside the progression of PH severity. A higher degree of RV fibrosis, derived from CMR imaging, correlates with worse hemodynamics, RV dysfunction, and poorer clinical conditions.

The impact of water exchange on estimates of myocardial extracellular volume calculated using contrast enhanced T1 measurements: A preliminary analysis in patients with severe aortic stenosis.

Guidelines recommend measuring myocardial extracellular volume (ECV) using T1 -mapping before and 10-30 min after contrast agent administration. Data are then analyzed using a linear model (LM), which assumes fast water exchange (WX) between the ECV and cardiomyocytes. We investigated whether limited WX influences ECV measurements in patients with severe aortic stenosis (AS). Twenty-five patients with severe AS and 5 healthy controls were recruited. T1 measurements were made on a 3 T Siemens system using a multiparametric saturation-recovery single-shot acquisition (a) before contrast; (b) 4 min post 0.05 mmol/kg gadobutrol; and (c) 4 min, (d) 10 min, and (e) 30 min after an additional gadobutrol dose (0.1 mmol/kg). Three LM-based ECV estimates, made using paired T1 measurements (a and b), (a and d), and (a and e), were compared to ECV estimates made using all 5 T1 measurements and a two-site exchange model (2SXM) accounting for WX. Median (range) ECV estimated using the 2SXM model was 25% (21%-39%) for patients and 26% (22%-29%) for controls. ECV estimated in patients using the LM at 10 min following a cumulative contrast dose of 0.15 mmol/kg was 21% (17%-32%) and increased significantly to 22% (19%-35%) at 30 min (p = 0.0001). ECV estimated using the LM was highest following low dose gadobutrol, 25% (19%-38%). Current guidelines on contrast agent dose for ECV measurements may lead to underestimated ECV in patients with severe AS because of limited WX. Use of a lower contrast agent dose may mitigate this effect.

Myocardial Fibrosis Improves in Young Patients with Sickle Cell Disease after Hematopoietic Cell Transplantation

Introduction: Cardiovascular complications are a leading cause of early mortality in patients with sickle cell disease (SCD). Chronic anemia, iron overload and repeated microvascular ischemic insults with reperfusion injury often result in progressive myocardial injury and maladaptive remodeling in SCD patients. Patients with SCD develop diffuse myocardial fibrosis, which can be detected by quantifying the myocardial extracellular volume (ECV) using cardiovascular magnetic resonance (CMR) imaging. Our group and others have previously shown that diffuse myocardial fibrosis is highly prevalent in both children and young adults with SCD, including those who have normal ventricular size and function by echocardiography. Additionally, we have shown that the disease modifying therapies (DMT) such as hydroxyurea or chronic transfusions do not appear to be protective against development of diffuse myocardial fibrosis. In a retrospective study, we found no difference in the myocardial ECV in patients who began DMT early (less than 6 years of age) versus later in life (at least 6 years or after) (Morin CE and Sharma A et al. Blood 2023.). Hematopoietic cell transplantation (HCT) can cure SCD, but myocardial effects of the therapy are unknown. Our goal was to evaluate cardiovascular parameters of function and injury, especially the progression of diffuse myocardial fibrosis, by comparing serial CMR studies performed before and after HCT in patients with SCD. Methods: We performed prospective CMR evaluation of children and young adults with SCD who received a matched sibling donor (MSD) or haploidentical donor (HAPLO) HCT following a reduced toxicity conditioning on a clinical trial (NCT04362293). CMR was performed pre-HCT, and at 1 month, and 12 months post-HCT. CMR-derived ventricular and atrial volumes were calculated. ECV was measured from T1 maps with a modified Look-Locker inversion recovery (MOLLI) sequence in short-axis. T2 and T2* maps were obtained. Regions of interest in the mid-ventricular septum were identified for analysis. We report descriptive statistics for CMR measures along with paired t-tests comparing patient ECV levels at 1-month and 12-months post-HCT to their respective baseline ECV. Results: Our study cohort consisted of 14 patients with SCD who underwent HCT and had serial CMR evaluations available. Thirteen patients had HbSS genotype and one had HbSC genotype. All patients were receiving DMT, either with hydroxyurea or chronic transfusions prior to HCT. Participants were majority male (57%) with median age of 15.2 years (range 6.8-21.3) at the pre-HCT CMR. Six received an MSD HCT and 8 received a HAPLO HCT. Ten patients each had follow up CMR evaluations performed at 1 month, and 12 months post-HCT. At 1 and 12 months post-HCT ejection fraction was preserved while biventricular volume and cardiac index decreased (Table 1). Compared to pre-HCT, ECV decreased from median 29% [range 27-38] to 28% (range 21-35, P= 0.061) at 1 month and 27% (range 24-31, P= 0.043) at 12 months post-HCT. There was no difference in the cardiac chamber sizes or the ECV measurements of those who received a MSD versus HAPLO HCT. Conclusions: We observed an improvement in cardiac chamber sizes with preservation of cardiac function as early as one month after HCT in patients with SCD. We further noted a reduction in ECV indicating a decrease in diffuse myocardial fibrosis in these young patients with SCD. To our knowledge, this is the first study to show that diffuse myocardial fibrosis can improve in patients with SCD after HCT. In addition to further corroborating the organ function protective effects of HCT in patients with SCD, these data further demonstrate the use of CMR as an essential non-invasive tool to assess the effects of therapeutic interventions on SCD-cardiac injury.

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

Quantification of extracellular volume with cardiac computed tomography in patients with left ventricle dysfunction

Abstract Background Myocardial fibrosis (MF) is a common endpoint in the majority of pathological mechanisms affecting cardiac muscle, ultimately resulting in cardiac failure. Cardiovascular magnetic resonance (CMR) with gadolinium-based contrast agent and T1 mapping technique is able to deliver a non-invasive quantification of the extracellular volume (ECV) expansion. Recently, ECV estimation with cardiac computed tomography (ECV-CCT) has been validated in the setting of cardiac amyloidosis, showing good agreement with ECV-CMR. However, no evidence is available with last generation single source single energy CT scanner in the clinical context of newly diagnosed left ventricular dysfunction. Therefore, the aim of this study is to test the diagnostic accuracy of ECV-CCT for the detection of MF in patients with recent diagnosis of reduced left ventricle ejection fraction (LVEF), having ECV-CMR as reference technique. Methods A consecutive cohort of 41 patients with newly diagnosed left ventricle dysfunction (LVEF &amp;lt; 50%) was enrolled. Time interval of maximum 30 days was present between CCT and CMR. Myocardial segment evaluability with each technique, agreement between ECV-CMR and ECV-CCT, regression analysis and Bland-Altman analysis were performed. Results Age of enrolled patients was 62 ± 11 years, and mean LVEF at CMR was 35.2 ± 10.7%. Mean total amount of administrated iodinated contrast was 112.6 ± 22.2 ml, while overall radiation exposure for ECV estimation was2.1 ± 1.1 mSv. Out of 656 myocardial segments available, 656 (100%) segments were evaluable at CCT while 640 (97.6%) were evaluable at CMR. ECV-CCT demonstrated slightly lower values compared to ECV-CMR both at global and region-based comparison (all segments, 33.1 ± 8.5% vs 35.5 ± 10.7%, p &amp;lt; 0.001). At regression analysis, strong correlations were described both at global and region-based analysis (all segments, r = 0.877, 95% CI: 0.840 to 0.914). On Bland-Altman analysis, bias between ECV-CMR and ECV-CCT for global analysis was 2.4 (95% CI: -7.8 to 12.7). Conclusions ECV estimation with last-generation single source single energy CT scanner is feasible and accurate. Integration of ECV measurement in comprehensive CCT evaluation of patients with newly diagnosed left ventricular dysfunction can be performed with a small increase in overall radiation exposure.

Abstract 11768: Regression of Inflammation by Cardiac Magnetic Resonance in Chronic Chagasic Patients Treated With Benznidazole

Introduction: Chagas disease (CD) is a neglected disease caused by Trypanosoma cruzi ( T. cruzi ), and benznidazole (BZN) is the most prescribed trypanocidal drug in Brazil in function of its best tolerability profile. While treatment with this drug is effective in acute disease, there is no consensus on its effectiveness in adults with chronic infection. Although it is now accepted that treatment directed against T. cruzi is necessary to avoid the long-term sequelae of the disease, the lack of reliable markers for assessment of treatment efficacy is a major obstacle to evaluating new drugs. Hypothesis: the objective of this study is to determine if BZN treatment reduces cardiac inflammation/fibrosis as assessed by magnetic resonance imaging (MRI), using parametric mapping techniques. Methods: Prospective, multi-center study of chronic CD patients underwent MRI T1 and T2 mapping and extracellular volume measurement (ECV) using the modified Look-Locker inversion recovery (MOLLI) sequence, undergoing treatment with BZN, at a dose of 300 mg/kg daily divided into two doses and taken for 60 days. Absolute change T1 and T2 mapping, ECV, left ventricular end-diastolic volume (LVEDV), left ventricular end-systolic volume (LVESV) and left ventricle ejection fraction (LVEF) were analyzed from baseline to 6-month follow-up. Results: 53 patients (females 83%, 53.9 ± 11.9 years old) were studied. LVEDV (149 ± 27ml vs 147 ± 29ml, p = 0.52), LVESV (66 ± 29 vs 64 ± 15, p = 0.65) and LVEF (55 ± 11% vs 57 ± 8%, p = 0,28) did not change between baseline and post treatment. Native T1 time showed reduced values among anterior (1030 ± 41ms vs 1011 ± 52ms, p = 0.011), septal (1052 ± 53ms vs 1006 ± 38ms, p = 0.000) and lateral (1042 ± 55ms vs 1019 ± 44ms, p = 0.003) LV walls. T2 mapping showed reduction in LV septal wall (53 ± 4ms vs 52 ± 3ms, p = 0.005). ECV showed significant reduction from baseline to 6-month follow-up (29.9 ± 3,3% vs 28.2 ± 3.5%, p = 0.0001). Conclusions: For the first time, we observe favorable changes in CMR ECV, T1 and T2 mapping induced by benznidazole therapy in chronic Chagas disease patients. These findings suggest that there may be an opportunity to decrease fibrosis/inflammation in chronic CD patients with the use of this therapeutic approach.

Quantification of myocardial extracellular volume without blood sampling.

Cardiac magnetic resonance (CMR) T1 relaxation time mapping is an established technique primarily used to identify diffuse interstitial fibrosis and oedema. The myocardial extracellular volume (ECV) can be calculated from pre- and post-contrast T1 relaxation times and is a reproducible parametric index of the proportion of volume occupied by non-cardiomyocyte components in myocardial tissue. The conventional calculation of the ECV requires blood sampling to measure the haematocrit (HCT). Given the high variability of the HCT, the blood collection is recommended within 24 h of the CMR scan, limiting its applicability and posing a barrier to the clinical routine use of ECV measurements. In recent years, several research groups have proposed a method to determine the ECV by CMR without blood sampling. This is based on the inverse relationship between the T1 relaxation rate (R1) of blood and the HCT. Consequently, a 'synthetic' HCT could be estimated from the native blood R1, avoiding blood sampling. We performed a review and meta-analysis of published studies on synthetic ECV, as well as a secondary analysis of previously published data to examine the effect of the chosen regression modell on bias. While, overall, a good correlation and little bias between synthetic and conventional ECV were found in these studies, questions regarding its accuracy remain. Synthetic HCT and ECV can provide a 'non-invasive' quantitative measurement of the myocardium's extracellular space when timely HCT measurements are not available and large alterations in ECV are expected, such as in cardiac amyloidosis. Due to the dependency of T1 relaxation times on the local setup, calculation of local formulas using linear regression is recommended, which can be easily performed using available data.

Half-Dose versus Single-Dose Gadobutrol for Extracellular Volume Measurements in Cardiac Magnetic Resonance.

Cardiac magnetic resonance (CMR) imaging with gadolinium-based contrast agents offers unique non-invasive insights into cardiac tissue composition. Myocardial extracellular volume (ECV) has evolved as an objective and robust parameter with broad diagnostic and prognostic implications. For the gadolinium compound gadobutrol, the recommended dose for cardiac imaging, including ECV measurements, is 0.1 mmol/kg (single dose). This dose was optimized for late enhancement imaging, a measure of focal fibrosis. Whether a lower dose is sufficient for ECV measurements is unknown. We aim to evaluate the accuracy of ECV measurements using a half dose of 0.05 mmol/kg gadobutrol compared to the standard single dose of 0.1 mmol/kg. From a contemporary trial (NCT04747366, registered 10 February 2021), a total of 25 examinations with available T1 mapping before and after 0.05 and 0.1 mmol/kg gadobutrol were analyzed. ECV values were calculated automatically from pre- and post-contrast T1 relaxation times. T1 and ECV Measurements were performed in the midventricular septum. ECV values after 0.05 and 0.1 mmol/kg gadobutrol were correlated (R2 = 0.920, p < 0.001). ECV values after 0.05 mmol/kg had a bias of +0.9% (95%-CI [0.4; 1.4], p = 0.002) compared to 0.1 mmol/kg gadobutrol, with limits of agreement from -1.5 to 3.3%. CMR with a half dose of 0.05 mmol/kg gadobutrol overestimated ECV by 0.9% compared with a full dose of 0.1 mmol/kg, necessitating adjustment of normal values when using half-dose ECV imaging.

Predictive value of total ischaemic time and T1 mapping after emergency percutaneous coronary intervention in acute ST-segment elevation myocardial infarction

To investigate the predictive value of ischaemic time and cardiac magnetic resonance imaging (CMRI) T1 mapping in acute ST-segment elevation myocardial infarction (STEMI) patients undergoing primary percutaneous coronary intervention (PCI). A total of 127 patients with STEMI treated by primary PCI were studied. All patients underwent CMRI with native T1 and extracellular volume (ECV) measurement, 61 of whom also had 4-month follow-up data. The total ischaemic (symptom onset to balloon, S2B) time expressed in minutes was recorded. CMRI cine, T1 mapping, and late gadolinium enhancement (LGE) images were analysed to evaluate left ventricular (LV) function, T1 value, ECV, and myocardial infract (MI) scar characteristics, respectively. The correlation between S2B time and T1 mapping was evaluated. The predictive values of S2B time and T1 mapping for large final infarct size were estimated. The incidence of microvascular obstruction (MVO) increased with the prolongation of ischaemia time. Regardless of MVO or not, ECV in myocardial infarction (ECVMI) was significantly correlated with S2B time (r=0.61, p<0.001), while native T1 in MI (T1MI) was not (r=-0.19, p=0.029). In the 4-month follow-up, native T1MI was improved (1385.1±90.4 versus 1288.6±74 ms, p<0.001). Furthermore, ECVMI was independently associated with final larger infarct size (AUC=0.89, 95% confidence interval [CI]=0.81-0.98, p<0.001) in multivariable regression analysis. ECVMI was correlated with total ischaemic time and was an independent predictor of final larger infarct size.