ECV Values Research Articles

Myocardial parametric mapping in patients with suspected acute myocarditis: a prognosis study

Abstract Background T1 mapping and T2 mapping have become essential components of the 2018 Lake Louise criteria and obtained excellent results in diagnosing myocarditis. However, their prognostic value in acute myocarditis has not yet been well recognized or established. Purpose Our study aims to investigate the prognostic value of T1 mapping, T2 mapping, and extracellular volume fraction (ECV) in a large cohort of patients with suspected acute myocarditis. Materials Patients meeting the recommended clinical criteria for suspected acute myocarditis were consecutively enrolled. The primary endpoint is the composite of cardiac death, heart failure hospitalization, heart transplantation, sustained ventricular arrhythmia, and recurrent myocarditis, defined as major adverse cardiovascular events (MACE). All patients underwent CMR at 3.0 T scanner using a standardized, routine imaging protocol, and the three short-axis view slices (basal, mid-ventricular, and apical) were divided into 16 segments according to the American Heart Association 17-segment model (apex excluded). We also averaged the native T1 values, ECV, and T2 values of all 16 segments to get global T1 and ECV fraction values, respectively. Statistically significant parameters from univariate Cox analyses were put into multivariate Cox analysis. Results A total of 235 patients (150 men; 32±13 years) were enrolled in this study. During a mean follow-up of 43.0±3.6 months, MACE occurred in 37 patients (15.7%) and was univariably associated with heart failure presentation, left ventricular ejection fraction, left ventricular end-systolic volume index, left ventricular end-diastolic volume index, native T1 and ECV. Patients with MACE showed higher global native T1, ECV, and T2 values (1348±59 vs 1266±51, p=<0.001; 40.0±8.7 vs 32.8±5.9, p<0.001; 63.4±12.1 vs. 55.5±9.1, p=0.011), and were more likely to have tissue changes in the interventricular septum and anterior wall (Figure 1). In a series of nesting multivariable Cox regression models, the addition of native T1 (per 10-ms increase: HR, 1.128; 95% CI: 1.043, 1.220; p = 0.003; Harrell’s C-index = 0.833) or ECV (per 5% increase: HR, 1.382; 95% CI: 1.060, 1.802; p = 0.017; Harrell’s C-index = 0.847) improved prognostication compared with the model based on clinical variables, left ventricular ejection fraction, and septal late gadolinium enhancement (Harrell’s C-index = 0.762) (Figure 2). T2 in multivariate Cox regression analysis didn’t show predictive value, but his inclusion increased the C-index of the model to 0.814. Conclusions Myocardial parametric mapping not only holds substantial diagnostic value but also plays a critical role in the prognostic assessment and risk prediction of myocarditis. Their utilization in these contexts enhances the accuracy and effectiveness of clinical evaluations and decision-making processes.

Distinguishing hypertensive cardiomyopathy from cardiac amyloidosis in hypertensive patients with heart failure: a CMR study with histological confirmation.

Differentiation of the cause of left ventricular hypertrophy (LVH) is challenging in cases with co-existing hypertension. CMR offers assessment of diffuse myocardial abnormalities via T1 mapping with extracellular volume fraction (ECV) and macroscopic fibrosis via late gadolinium enhancement imaging (LGE). The goal of the study was to understand if CMR parameters can differentiate hypertensive cardiomyopathy (HC) from cardiac amyloidosis (CA) in patients with hypertension and heart failure, using endomyocardial biopsy (EMB) as the gold standard. We retrospectively analyzed patients with hypertension, LVH, and heart failure undergoing EMB due to uncertain diagnosis. CMR parameters including cine, LGE characteristics, T1 mapping, and ECV were analyzed. A total of 34 patients were included (mean age 66.5 ± 10.7 years, 79.4% male). The final EMB-based diagnosis was HC (10, 29%), light chain (AL) CA (7, 21%), and transthyretin (ATTR) CA (17, 50%). There was a significant difference in subendocardial LGE (p = 0.03) and number of AHA segments with subendocardial LGE (p = 0.005). The subendocardial LGE pattern was most common in AL-CA (85.7%) and African American with HC (80%). ECV elevation (≥ 29%) was present in all patients with CA (AL-CA: 57.6 ± 5.2%, ATTR-CA: 59.1 ± 15.3%) and HC (37.3 ± 4.5%). Extensive subendocardial LGE pattern is not pathognomonic for CA but might also be present in African American patients with longstanding or poorly controlled HTN. The ECV elevation in HC with HF might be more significant than previously reported with an overlap of ECV values in HC and CA, particularly in younger African American patients.

Predictors of lung cancer subtypes and lymph node status in non-small-cell lung cancer: intravoxel incoherent motion parameters and extracellular volume fraction

ObjectiveTo determine the performance of intravoxel incoherent motion (IVIM) parameters and the extracellular volume fraction (ECV) in distinguishing between different subtypes of lung cancer and predicting lymph node metastasis (LNM) status in patients with non-small-cell lung cancer (NSCLC).MethodsOne hundred sixteen patients with lung cancer were prospectively recruited. IVIM, native, and postcontrast T1 mapping examinations were performed, and the T1 values were measured to calculate the ECV. The differences in IVIM parameters and ECV were compared between NSCLC and small-cell lung cancer (SCLC), adenocarcinoma (Adeno-Ca) and squamous cell carcinoma (SCC), and NSCLC without and with LNM. The assessment of each parameter’s diagnostic performance was based on the area under the receiver operating characteristic curve (AUC).ResultsThe apparent diffusion coefficient (ADC), true diffusion coefficient (D), and ECV values in SCLC were considerably lower compared with NSCLC (all p < 0.001, AUC > 0.887). The D value in SCC was substantially lower compared with Adeno-Ca (p < 0.001, AUC = 0.735). The perfusion fraction (f) and ECV values in LNM patients were markedly higher compared with those without LNM patients (p < 0.01, < 0.001, AUC > 0.708).ConclusionIVIM parameters and ECV can serve as non-invasive biomarkers for assisting in the pathological classification and LNM status assessment of lung cancer patients.Critical relevance statementIVIM parameters and ECV demonstrated remarkable potential in distinguishing pulmonary carcinoma subtypes and predicting LNM status in NSCLC.Key PointsLung cancer is prevalent and differentiating subtype and invasiveness determine the treatment course.True diffusion coefficient and ECV showed promise for subtyping and determining lymph node status.These parameters could serve as non-invasive biomarkers to help determine personalized treatment strategies.Graphical

Left ventricular reverse remodeling and reduction of interstitial fibrosis in patients with severe aortic stenosis who underwent transcatheter aortic valve implantation

BackgroundLeft ventricular (LV) structural and functional changes have been reported in patients with aortic stenosis (AS) who have undergone transcatheter aortic valve implantation (TAVI); however, the relationship between change in LV structure and systolic function and tissue characteristics assessed via cardiovascular magnetic resonance imaging (CMRI) post-TAVI has been not fully elucidated. This study aimed to investigate this relationship in patients with severe AS who underwent TAVI and CMRI. MethodsIn this retrospective study, 65 patients who underwent TAVI and CMRI at the 6-month follow-up were analyzed. The relationship between percent changes in LV end-diastolic volume (LVEDV), LV end-systolic volume (LVESV), LV ejection fraction (LVEF), and LV mass (LVM) (⊿LVEDV, ⊿LVESV, ⊿LVEF, and ⊿LVM) and those in the native T1 value (⊿native T1) was analyzed using a correlation analysis. Moreover, extracellular volume fraction (ECV) value changes were analyzed. ResultsThe ⊿native T1 significantly decreased from 1292.8 (1269.9–1318.4) ms at pre-TAVI to 1282.3 (1262.6–1310.2) ms at the 6-month follow-up (P = 0.022). A significant positive correlation between ⊿LVEDV, ⊿LVESV, and ⊿LVM and ⊿native T1 (r = 0.351, P = 0.004; r = 0.339, P = 0.006; r = 0.261, P = 0.035, respectively) and a tendency toward a negative correlation between ⊿LVEF and ⊿native T1 (r = −0.237, P = 0.058) were observed. The ECV value increased significantly from 26.7 % (25.3–28.3) to 28.2 % (25.7–30.5) (P = 0.002). ConclusionsThe decrease in native T1 might be associated with LV reverse remodeling. Evaluating structural and functional changes using CMRI may be useful for patient management.

Changes in subclinical cardiac abnormalities 1 Year after recovering from COVID-19 in patients without clinical cardiac findings

AimTo evaluate the subclinical cardiac involvement in COVID-19 patients without clinical cardiac evidence using cardiac MR imaging. Material and methodsParticipants recovered from COVID-19 without cardiac symptoms and no cardiovascular medical history were enrolled in a prospective cohort study. They underwent baseline cardiac MR and follow-up cardiac MR > 300 days after discharge (n = 20). The study also included healthy controls (n = 20). Extracellular volume fraction (ECV), native T1, and 2D strain data were assessed and compared. ResultsThe ECV values of participants at baseline [30.0% (28.3%–32.5%)] and at follow-up [31.0% (28.0%–32.8%)] were increased compared to the healthy control group [27.0% (25.3%–28.0%)] (both p < 0.001). However, the ECV increase from baseline cardiac MR to follow-up cardiac MR was not significant (p = 0.378). There was a statistically significant difference in global native T1 between baseline [1140 (1108.3–1192.0) ms] and follow-up [1176.0 (1113.0–1206.3) ms] (p = 0.016). However, no native T1 difference was found between the healthy controls [1160.7 (1119.6–1195.4) ms] and the baseline (p = 0.394) or follow-up group (p = 0.168). The global T2 was 41(40–42) ms at follow-up which was within the normal range. In addition, We found a recovery in 2D GLS among COVID-19 participants between baseline and follow-up [-12.4(-11.7 to −14.3)% vs. −17.2(-16.2 to −18.3)%; p＜0.001]. ConclusionUsing cardiac MR myocardial tissue and strain imaging parameters, 35% of people without cardiac symptoms or clinical evidence of myocardial injury still had subclinical myocardial tissue characteristic abnormalities at 300 days, but 2D GLS had recovered.

Prognostic value of native T1 and extracellular volume in patients with immunoglubin light-chain amyloidosis

BackgroundCardiac involvement in patients with immunoglubin light-chain amyloidosis (AL) is a major determinant of treatment choice and prognosis, and early identification of high-risk patients can initiate intensive treatment strategies to achieve better survival. This study aimed to investigate the prognostic value of native T1 and ECV in patients with AL-cardiac amyloidosis (CA).MethodsA total of 38 patients (mean age 59 ± 11 years) with AL diagnosed histopathologically from July 2017 to October 2021 were collected consecutively. All patients were performed 3.0-T cardiac magnetic resonance (CMR) including cine, T1 mapping, and late gadolinium enhancement (LGE). Pre- and post-contrast T1 mapping images were transferred to a dedicated research software package (CVI42 v5.11.3) to create parametric T1 and ECV values. In addition, clinical and laboratory data of all patients were collected, and patients or their family members were regularly followed up by telephone every 3 months. The starting point of follow-up was the time of definitive pathological diagnosis, and the main endpoint was all-cause death. Kaplan-Meier analysis and Cox proportional risk model were used to evaluate the association between native T1 and ECV and death in patients with CA.ResultsAfter a median follow-up of 27 (16, 37) months, 12 patients with CA died. Kaplan-Meier analysis showed that elevated native T1 and ECV were closely associated with poor prognosis in patients with CA. The survival rate of patients with ECV > 44% and native T1 > 1389ms were significantly lower than that of patients with ECV ≤ 44% and native T1 ≤ 1389ms (Log-rank P < 0.001), and was not associated with the presence of LGE. After adjusting for clinical risk factors and CMR measurements in a stepwise multivariate Cox regression model, ECV [risk ratio (HR):1.37, 95%CI: 1.09–1.73, P = 0.008] and native T1 (HR:1.01, 95%CI: 1.00-1.02, P = 0.037) remained independent predictors of all-cause mortality in patients with CA.ConclusionsBoth native T1 and ECV were independently prognostic for mortality in patients with CA, and can be used as important indicators for clinical prognosis assessment of AL.

Myocardial involvement characteristics by cardiac MR imaging in neurological and non-neurological Wilson disease patients

ObjectivesTo explore the characteristics of myocardial involvement in Wilson Disease (WD) patients by cardiac magnetic resonance (CMR).MethodsWe prospectively included WD patients and age- and sex-matched healthy population. We applied CMR to analyze cardiac function, strain, T1 maps, T2 maps, extracellular volume fraction (ECV) maps, and LGE images. Subgroup analyzes were performed for patients with WD with predominantly neurologic manifestations (WD‐neuro +) or only hepatic manifestations (WD‐neuro −).ResultsForty-one WD patients (age 27.9 ± 8.0 years) and 40 healthy controls (age 25.4 ± 2.9 years) were included in this study. Compared to controls, the T1, T2, and ECV values were significantly increased in the WD group (T1 1085.1 ± 39.1 vs. 1046.5 ± 33.1 ms, T2 54.2 ± 3.3 ms vs. 51.5 ± 2.6 ms, ECV 31.8 ± 3.6% vs. 24.3 ± 3.7%) (all p < 0.001). LGE analysis revealed that LGE in WD patients was predominantly localized to the right ventricular insertion point and interventricular septum. Furthermore, the WD‐neuro + group showed more severe myocardial damage compared to WD‐neuro − group. The Unified Wilson Disease Rating Scale score was significantly correlated with ECV (Pearson’s r = 0.64, p < 0.001).ConclusionsCMR could detect early myocardial involvement in WD patients without overt cardiac function dysfunction. Furthermore, characteristics of myocardial involvement were different between WD‐neuro + and WD‐neuro − , and myocardial involvement might be more severe in WD‐neuro + patients.Critical relevance statementCardiac magnetic resonance enables early detection of myocardial involvement in Wilson disease patients, contributing to the understanding of distinct myocardial characteristics in different subgroups and potentially aiding in the assessment of disease severity.Key points• CMR detects WD myocardial involvement with increased T1, T2, ECV.• WD‐neuro + patients show more severe myocardial damage and correlation with ECV.• Differences of myocardial characteristics exist between WD‐neuro + and WD‐neuro − patients.Graphical

In vitro characterization and molecular epidemiology of Cryptococcus spp. isolates from non-HIV patients in Guangdong, China.

The burden of cryptococcosis in mainland China is enormous. However, the in vitro characterization and molecular epidemiology in Guangdong, a key region with a high incidence of fungal infection in China, are not clear. From January 1, 2010, to March 31, 2019, clinical strains of Cryptococcus were collected from six medical centres in Guangdong. The clinical information and characteristics of the strains were analysed. Furthermore, molecular types were determined. A total of 84 strains were collected, mostly from male and young or middle-aged adult patients. Pulmonary and cerebral infections (82.1%) were most common. All strains were Cryptococcus neoformans, grew well at 37°C and had capsules around their cells. One melanin- and urea- and one melanin+ and urea- variants were found. Although most strains exhibited a low minimum inhibitory concentration (MIC) value for voriconazole (mean: 0.04 μg/mL) and posaconazole (mean: 0.12 μg/mL), the results for these isolates showed a high degree of variation in the MIC values of fluconazole and 5-fluorocytosine, and resistance was observed for 4 out of 6 drugs. A significant proportion of these strains had MIC values near the ECV values, particularly in the case of amphotericin B. The proportion of strains near the clinical breakpoints was as follows: fluconazole: 3.66%; voriconazole: 3.66%; itraconazole: 6.10%; posaconazole: 13.41%; amphotericin B: 84.15%; 5-fluorocytosine: 2.44%. These strains were highly homogeneous and were dominated by the Grubii variant (95.2%), VNI (94.0%), α mating (100%), and ST5 (89.3%) genotypes. Other rare types, including ST4, 31, 278, 7, 57 and 106, were also found. Phenotypically variant and non-wild-type strains were found in Guangdong, and a significant proportion of these strains had MIC values near the ECV values towards the 6 antifungal drugs, and resistance was observed for 4 out of 6 drugs. The molecular type was highly homogeneous but compositionally diverse, with rare types found. Enhanced surveillance of the aetiology and evolution and continuous monitoring of antifungal susceptibility are needed to provide references for decision-making in the health sector and optimization of disease prevention and control.

Clinical Utility of Computed Tomography–Derived Myocardial Extracellular Volume Fraction: A Systematic Review and Meta-Analysis

BackgroundComputed tomography (CT)–derived extracellular volume fraction (ECV) is a noninvasive method to quantify myocardial fibrosis. Although studies suggest CT is a suitable measure of ECV, clinical use remains limited. ObjectivesA meta-analysis was performed to determine the clinical value of CT-derived ECV in cardiovascular diseases. MethodsElectronic database searches of PubMed, Web of Science Core Collection, Cochrane advanced search, and EMBASE were performed. The most pivotal analysis entailed the comparison of ECV ascertained through CT-ECV among the control, aortic stenosis, and cardiac amyloidosis cohorts. The diagnostic test accuracy for detecting cardiac amyloidosis was assessed using summary receiver-operating characteristics curve. ResultsPooled CT-derived ECV values were 28.5% (95% CI: 27.3%-29.7%) in the control, 31.9% (95% CI: 30.2%-33.8%) in the aortic stenosis, and 48.9% (95% CI: 44.5%-53.3%) in the cardiac amyloidosis group. ECV was significantly elevated in aortic stenosis (P = 0.002) (vs controls) but further elevated in cardiac amyloidosis (P < 0.001) (vs aortic stenosis). CT-derived ECV had a high diagnostic accuracy for cardiac amyloidosis, with sensitivity of 92.8% (95% CI: 86.7%-96.2%), specificity of 84.8% (95% CI: 68.6%-93.4%), and area under the summary receiver-operating characteristic curve of 0.94 (95% CI: 0.88-1.00). ConclusionsThis study is the first comprehensive systematic review and meta-analysis of CT-derived ECV evaluation in cardiac disease. The high diagnostic accuracy of CT-ECV suggests the usefulness of CT-ECV in the diagnosis of cardiac amyloidosis in preoperative CT planning for transcatheter aortic valve replacement.

Dynamic changes in cardiac morphology, function, and diffuse myocardial fibrosis duration of diabetes in type 1 and type 2 diabetic mice models using 7.0 T CMR and echocardiography.

Diabetes mellitus (DM) is associated with an increased risk of cardiovascular disease (CVD). Hence, early detection of cardiac changes by imaging is crucial to reducing cardiovascular complications. Early detection of cardiac changes is crucial to reducing cardiovascular complications. The study aimed to detect the dynamic change in cardiac morphology, function, and diffuse myocardial fibrosis(DMF) associated with T1DM and T2DM mice models. 4-week-old C57Bl/6J male mice were randomly divided into control (n=30), T1DM (n=30), and T2DM (n=30) groups. A longitudinal study was conducted every 4 weeks using serial 7.0T CMR and echocardiography imaging. Left ventricular ejection fraction (LV EF), tissue tracking parameters, and DMF were measured by cine CMR and extracellular volume fraction (ECV). Global peak circumferential strain (GCPS), peak systolic strain rate (GCPSSR) values were acquired by CMR feature tracking. LV diastolic function parameter (E/E') was acquired by echocardiography. The correlations between the ECV and cardiac function parameters were assessed by Pearson's test. A total of 6 mice were included every 4 weeks in control, T1DM, and T2DM groups for analysis. Compared to control group, an increase was detected in the LV mass and E/E' ratio, while the values of GCPS, GCPSSR decreased mildly in DM. Compared to T2DM group, GCPS and GCPSSR decreased earlier in T1DM(GCPS 12W,P=0.004; GCPSSR 12W,P=0.04). ECV values showed a significant correlation with GCPS and GCPSSR in DM groups. Moreover, ECV values showed a strong positive correlation with E/E'(T1DM,r=0.757,P<0.001;T2DM, r=0.811,P<0.001). The combination of ECV and cardiac mechanical parameters provide imaging biomakers for pathophysiology, early diagnosis of cardiac morphology, function and early intervention in diabetic cardiomyopathy in the future.

Abstract 13430: Cardiovascular Magnetic Resonance Imaging for Comprehensive Risk Assessment in Patients With Aortic Stenosis

Introduction: Precise risk assessment is essential for accurate management of patients with severe aortic stenosis (AS) undergoing transcatheter aortic valve replacement (TAVR). This study aimed to assess the prognostic implications of cardiovascular magnetic resonance (CMR)-derived imaging biomarkers in a large cohort of AS patients. Methods: 145 patients with severe AS underwent CMR imaging before TAVR. Image analyses included myocardial volumes, CMR-feature-tracking derived left and right atrial (LA &amp; RA) as well as left and right ventricular (LV &amp; RV) strain, myocardial T1 mapping as well as late gadolinium enhancement analyses. Cardiovascular (CV) mortality was defined as primary clinical endpoint. Results: Patients with CV death during follow-up had significantly enlarged RV enddiastolic volumes (82.9ml/ml 2 [70.8-96.0] vs. 62.8ml/ml 2 [54.7-76.0], p&lt;0.001) and impaired strain values of all cardiac chambers compared to patients that survived (LV GLS: -18.1% [-13.1- -20.4] vs. -22.5% [-16.1- -27.3], p=0.019; RV GLS: -22.9% [-18.6 - -25.4] vs. -27.9% [-22.9- -32.0], p=0.002; LA Es: 9.5% [7.2 - 15.4] vs. 14.3% [9.0-18.1], p=0.036; RA Es: 12.4% [6.8-14.4] vs. 16.2% [11.2-22.1], p&lt;0.001). RA reservoir strain independently predicted CV mortality after adjusting for other CMR imaging biomarkers and clinical parameters of heart failure. Within patients with high ECV values especially RA strain further identified AS patients at high-risk for CV mortality (p=0.001 on log-rank testing). Conclusion: Comprehensive CMR-imaging allows accurate outcome assessment and additional identification of high-risk groups in AS patients. Especially RA strain emerged as independent predictor for cardiovascular mortality and might serve for future optimized patient management.

Myocardial Fibrosis in Sickle Cell Anemia

Introduction Cardiovascular disease is a leading cause of morbidity and mortality in patients with sickle cell disease (SCD) as they age.Contrast-enhanced cardiac MRI has been utilized to evaluate myocardial fibrosis by calculating the extracellular matrix volume fraction (ECV) from pre and post-contrast T1 mapping. Recent research in both animal and human models reveal that SCD patients have elevated ECV suggestive of myocardial fibrosis and is associated with diastolic dysfunction. The effects of current first-line therapies, chronic transfusions (CTT) or hydroxyurea (HU), on myocardial fibrosis are unknown and at present, there is conflicting data regarding their benefits. At our institution, SCD patients are treated early with either hydroxyurea, chronic transfusions, or both. We aimed to determine whether current disease-modifying therapies differentially affect myocardial fibrosis. Methods This was a single-center, retrospective cohort study of chronically transfused SCD patients and SCD patients on HU and/or CTT at Children's Hospital of Los Angeles between 2017 and 2022 aiming to assess clinical biomarkers associated with elevated ECV in sickle cell disease. This study was reviewed and approved by the Children's Hospital Los Angeles Institutional Review Board. All patients underwent cardiac MRI for clinical assessment of myocardial iron, cardiac enlargement, and myocardial fibrosis. Continuous variables are expressed as mean±standard deviation for normally distributed data and median [interquartile range] for non-normally distributed data. Parametric and non-parametric testing were used where appropriate and c-square testing was used for categorical variables. Results A total of 63 SCD patients, mean age 17.3±5.9 years (range 5-36yo), who underwent contrast-enhanced cardiac MRI imaging between 2017 and 2022 were included in this study: 27 CTT; 43 HU; and 7 healthy participants, mean age 15.4±2.4 years. There was no difference in age between treatment groups, nor healthy and SCD participants. There were 6 SCD patients not on any therapy and 13 patients on both. The ECV was elevated in SCD versus healthy (31.3% [27.9, 35] vs 26% [23.7,27.2], P=0.0003). There was no significant difference between the ECV values of patients on CTT, HU, both or no therapy, P=0.56 (Fig.1A). There was no difference in average length of therapy between CTT or HU, mean 10.4±4.9 vs 10.2±5.2 years and no association between length of therapy and ECV. We found positive correlation of E/A ratio with ECV in patients with SCD regardless of therapy (Spearmans rho 0.34, P=0.008), suggesting an association with left ventricular (LV) restrictive physiology. ECV was associated with increased WBC count (rho +0.28, P=0.03), AST (rho +0.3, P=0.02), decreased GFR (P=0.02), and decreased hemoglobin (rho -0.41, P=0.0013) (Fig.1B), while there was a trend toward increased urine microalbumin (rho +0.41, P=0.09). Discussion Fibrosis is likely due to prolonged, continuous exposure to inadequate myocardial oxygen supply and cardiac microvascular disease. Amelioration of myocardial fibrosis likely requires consistent, effective CTT or HU therapy as suggested by the Cincinnati/CHLA study. The HU patients in that study had documented high MCV or HbF over many years before ECV was measured. St Jude's study was prospective but follow-up was only 2 years and not compared to an untreated or poorly treated cohort. The sum of these studies suggests that protection from fibrosis may only be seen with continual protection from anemia/microvascular disease. This hypothesis remains to be proven. While we did not see a differential effect of hydroxyurea vs. chronic transfusion therapy, it is important to put this data into the context of SCD therapies and their indications. CTT is generally reserved for the most severe vascular disease phenotypes, such as stroke. Hydroxyurea is often prescribed but not always adhered to. The ECV range in our cohort was lower than that found in the original Cincinnati cohort, mean 44%±8, but similar to that found in the St. Jude cohort, median 30% [IQR 28,34] (Fig.1A). Lastly, elevated ECV correlates with anemia, a modifiable risk factor; restrictive LV physiology; and decreased estimated GFR, which may hint at similar etiologies. In summary, ECV is a clinically relevant cardiovascular biomarker and current preventative therapies may ameliorate but not abrogate myocardial fibrosis.

Cardiac MRI as a possible alternative to echocardiography for therapeutic response monitoring in ATTR cardiomyopathy: a multiparametric evaluation in patisiran treated patients

Abstract Funding Acknowledgements Type of funding sources: None. Background Cardiac amyloidosis (CA) is characterized by the extracellular deposition of amyloid fibrils in the heart, mostly light chain (AL) and transthyretin (ATTR) amyloidosis. Recent data have improved both the recognition and treatment of ATTR CA. The therapeutic advances in ATTR CA led to improvement in survival and quality of life, but less detailed evidence is available for the myocardial changes during treatment. Purpose The aim of this pilot study is to evaluate cardiac response under treatment with the genetic "silencer" patisiran in patients with mixed phenotype ATTR with an indication for neuropathy, using multimodal imaging techniques. Methods We prospectively evaluated consecutive patients with mixed phenotype v-ATTR amyloidosis who had received patisiran for aggravated polyneuropathy since 2021. All patients had a complete clinical, paraclinical and comprehensive echocardiography evaluation including myocardial deformation assessment, prior to receiving patisiran and at most recent follow-up. Five of our patient had complementary cardiac magnetic resonance (CMR) at baseline and 1 year follow-up. Results We included 13 patients (mean age 48.1±5.4 yo, 4 men) monitored for the therapeutic response based on the current ESC expert consensus on the monitoring of ATTR CA. They have all been diagnosed with variant ATTR with the same mutation - Glu54Gln - with severe mixed phenotype: both cardiac involvement and autonomous and peripheral polyneuropathy. Time since first diagnosis was 3.4 ±0.8 years, and they had all received Tafamidis 20 mg before being switched to patisiran. At 1 year of treatment, there was no significant change in NYHA functional class, but 6 MWT could not be performed due to impairment related to polyneuropathy. There was no significant change in NT-proBNP during treatment (median at baseline 543 pg/ml vs follow-up 255 pg/ml, p = 0.75). Echocardiography showed no significant change in LV maximal wall thickness (MWT), LV mass index (LVMi), LVEF, stroke volume and myocardial deformation (LV GLS) (Table). Based on these echocardiographic and biological parameters we considered our patients stationary. Meanwhile, CMR confirmed no significant difference between baseline and follow-up in LVMi, MWT and LVEF. Moreover, there was no difference in the visually assessed LGE distribution, native T1, T2 and ECV values (Table, Case vignette). Based on the tissue characterization all patients were considered stable regarding ATTR-CA evolution. We found strong correlations between echo and MRI for LVEF (r=0.71), LVEDV (r=0.67) and MWT (r=0.66). Conclusions Even if used after more than 3 years from first diagnosis in our cohort, structural and functional cardiac parameters remain stable under patisiran therapy. Our study highlights the utility of introducing CMR as an alternative to echocardiography in ATTR-CA disease monitoring protocols, based on its high accuracy, strong correlations and complexity of derived parameters.

Myocardial tissue microstructure with and without stress-induced ischemia assessed by T1 mapping in patients with stable coronary artery disease

BackgroundStress-induced myocardial ischemia seems not to be associated with cardiovascular events. However, its effects on myocardial tissue characteristics remain under debate. Thus, we sought to assess whether documented stress-induced ischemia is associated with changes in myocardial microstructure evaluated by magnetic resonance native T1 map and extracellular volume fraction (ECV). MethodsThis is a single-center, analysis of the previously published MASS V Trial. Multivessel patients with a formal indication for myocardial revascularization and with documented stress-induced ischemia were included in this study. Native T1 and ECV values evaluated by cardiac magnetic resonance imaging of ischemic and nonischemic myocardial segments at rest and after stress were compared. Myocardial ischemia was detected by either nuclear scintigraphy or stress magnetic cardiac resonance protocol. ResultsBetween May 2012 and March 2014, 326 prospective patients were eligible for isolated CABG or PCI and 219 were included in the MASS V trial. All patients underwent resting cardiac magnetic resonance imaging. Of a total of 840 myocardial segments, 654 were nonischemic segments and 186 were ischemic segments. Native T1 and ECV values of ischemic segments were not significantly different from nonischemic segments, both at rest and after stress induction. In addition, native T1 and ECV values of myocardial segments supplied by vessels with obstructive lesions were similar to those supplied by nonobstructive ones. Conclusion and relevanceIn this study, cardiac magnetic resonance identified similar T1 mapping values between ischemic and nonischemic myocardial segments. This finding suggests integrity and stability of myocardial tissue in the presence of stress-induced ischemia.

Association of myocardial iron deficiency based on T2* CMR with the risk of mild left ventricular dysfunction in HIV-1-infected patients.

This study sought to noninvasively determine myocardial iron levels in HIV-1-infected patients using CMR and explore the association between T2* values and mild left ventricular systolic dysfunction (LVSD). This prospective study was conducted from June 2019 to July 2021. HIV-1-infected adults and healthy controls were consecutively enrolled for CMR exam. CMR exam included the assessment of myocardium iron content (T2*), cardiac function (cine), inflammation (T2), and fibrosis (through extracellular volume fraction [ECV] and late gadolinium enhancement [LGE]) measurements. Mild LVSD is defined as a left ventricular ejection fraction (LVEF) between 40% and 49%. Of 47 HIV-1-infected patients enrolled, 12 were diagnosed with mild LVSD (HIV-1+/LEVF+) and 35 were diagnosed with preserved LV function (HIV-1+/LEVF-). Compared with healthy controls, HIV-1-infected patients displayed higher T2*, T1, T2, ECV values and lower global circumferential strain (GCS) and global radial strain (GRS) (all P < 0.05). However, between patients with and without mild LVSD, only the T2* values and ECV (all P <0.05) were different. The association between increased T2* values (>26 ms) and mild LVSD remained significant after adjusting for the established univariate predictors (ECV >32.9%, T1 values >1336 ms) of mild LVSD (odds ratio [OR], 10.153; 95% confidence interval [CI] 1.565-65.878, P = 0.015). Myocardial T2* values were elevated in HIV-1-infected patients, supporting the notion that ID was associated with mild LVSD. Our findings highlight the potential for ID in HIV-1-infected patients as an auxiliary biomarker to monitor the course of LVSD.

Myocardial Tissue-Level Characteristics of Adults With Metabolically Healthy Obesity

BackgroundIt remains unclear whether adults with metabolically healthy obesity (MHO) have altered myocardial tissue-level characteristics. ObjectivesThis study aims to assess the subclinical myocardial tissue-level characteristics of adults with MHO. MethodsThe EARLY-MYO-OBESITY (EARLY Assessment of MYOcardial Tissue Characteristics in OBESITY; NCT05277779) registry was a prospective, 3-center, cardiac imaging study of obese nondiabetic individuals without cardiac symptoms who underwent cardiac magnetic resonance. Myocardial tissue-level characteristics, including extracellular volume fraction (ECV) and native T2 values, were measured as indicators of myocardial fibrosis and edema. Global longitudinal peak systolic strain and early diastolic longitudinal strain rate were assessed by tissue tracking analysis to detect subclinical systolic and diastolic dysfunction. ResultsA total of 120 participants were included: MHO (n = 32; mean age, 38 years; 41% men), metabolically healthy controls without obesity (n = 32; mean age: 37 years; 41% men), and metabolically unhealthy obesity (MUHO) (n = 56; mean age: 37 years; 55% men). The MHO group had higher ECV and native T2 values than healthy controls (both P < 0.001); furthermore, the ECV was higher in the MUHO group than in the MHO group (P = 0.002). The prevalence of myocardial fibrosis was 44% (14 of 32) in the MHO group and 71% (40 of 56) in the MUHO group. Although there was no intergroup difference in left ventricular ejection fraction, the MHO group had reduced global longitudinal peak systolic and early diastolic longitudinal strain rates, indicating subclinical systolic and diastolic dysfunction. Multivariate regression analysis identified increased body mass index to be an independent risk factor for myocardial fibrosis (OR: 6.28 [95% CI: 3.17-12.47]; P < 0.001). ConclusionsThis study provides the first evidence of subclinical myocardial tissue-level remodeling in adults with obesity, regardless of metabolic health. Early identification of cardiac impairment may facilitate preventive strategies against heart failure in the MHO population. (EARLY Assessment of MYOcardial Tissue Characteristics in OBESITY [EARLY-MYO-OBESITY]; NCT05277779)

T1 mapping and extracellular volume fraction measurement to evaluate the poor-prognosis factors in patients with cervical squamous cell carcinoma.

To evaluate the clinical feasibility of T1 mapping and extracellular volume fraction (ECV) measurement in assessing prognostic factors in patients with cervical squamous cell carcinoma (CSCC). A total of 117 CSCC patients and 59 healthy volunteers underwent T1 mapping and diffusion-weighted imaging (DWI) on a 3 T system. Native T1 , contrast-enhanced T1 , ECV, and apparent diffusion coefficient (ADC) were calculated and compared based on surgico-pathologically verified deep stromal infiltration, parametrial invasion (PMI), lymphovascular space invasion (LVSI), lymph node metastasis, stage, histologic grade, and the Ki-67 labeling index (LI). Native T1 , contrast-enhanced T1 , ECV, and ADC values were significantly different between CSCC and the normal cervix (all p< 0.05). No significant differences were observed in any parameters of CSCC when the tumors were grouped by stromal infiltration or lymph node status, respectively (all p> 0.05). In subgroups of the tumor stage and PMI, native T1 was significantly higher for advanced-stage (p= 0.032) and PMI-positive CSCC (p= 0.001). In subgroups of the grade and Ki-67 LI, contrast-enhanced T1 was significantly higher for high-grade (p= 0.012) and Ki-67 LI ≥ 50% tumors (p= 0.027). ECV was significantly higher in LVSI-positive CSCC than in LVSI-negative CSCC (p< 0.001). ADC values showed a significant difference for the grade (p< 0.001) but none for the other subgroups. Both T1 mapping and DWI could stratify the CSCC histologic grade. In addition, T1 mapping and ECV measurement might provide more quantitative metrics for noninvasively predicting poor prognostic factors and aiding in preoperative risk assessment in CSCC patients.

Comparison of Four Mechanical Insufflation-Exsufflation Devices: Effect of Simulated Airway Collapse on Cough Peak Flow.

Mechanical insufflation-exsufflation (MI-E) devices are used to improve airway clearance in individuals with acute respiratory failure. Some MI-E devices measure cough peak flow (CPF) during MI-E to optimize pressure adjustments. The aim was to compare CPF and effective cough volume (ECV: volume expired/coughed > 3 L/s) measurements between 4 MI-E devices under simulated conditions of stable versus collapsed airway. Four MI-E devices were tested on the bench. Each device was connected via a standard circuit to a collapsible tube placed in an airtight chamber that was attached to a lung model with adjustable compliance and resistance. Pressure was measured upstream and downstream the collapsing tube; air flow was measured between the chamber and the lung model. Each device was tested in 2 conditions: collapse condition (0 cm H2O) and no-collapse condition (-70 cm H2O). For each condition, 6 combinations of inspiratory/expiratory pressures were applied. CPF was measured at the "mouth level" by the device built-in flow meter and at the "tracheal level" by a dedicated pneumotachograph. Comparisons were performed with non-parametric tests. CPF values measured at the tracheal level and ECV values differed between devices for each inspiratory/expiratory pressure in the collapse and no-collapse conditions (P < .001). CPF values were significantly lower at the tracheal level in the collapse as compared with the no-collapse condition (P < .001 for each device), whereas they were higher at the mouth level (P < .05) for 3 of the 4 devices. CPF values differed significantly across MI-E devices, highlighting limitation(s) of using only CPF values to determine cough effectiveness. In simulated of airway collapse, CPF increased at the mouth, whereas it decreased at the tracheal level.

High-resolution spatiotemporal changes in dominant frequency and structural organization during persistent atrial fibrillation.

Analyze changes in frequency activity and structural organization that occur over time with persistent atrial fibrillation (AF). Little is known about the frequency characteristics of the epicardium during transition from paroxysmal to persistent AF. Accurate identification of areas of high dominant frequency (DF) is often hampered by limited spatial resolution. Improvements in electrode arrays provide high spatiotemporal resolution, allowing for characterization of the changes that occur during this transition. AF was induced in adult Yorkshire swine by atrial tachypacing. DF mapping was performed using personalized mapping arrays. Histological analysis and late gadolinium enhanced magnetic resonance imaging were performed to determine structural differences in fibrosis. The left atrial epicardium was associated with a significant increase in DF in persistent AF (6.5 ± 0.2 vs. 7.4 ± 0.5 Hz, P = 0.03). The organization index (OI) significantly decreased during persistent AF in both the left atria (0.3 ± 0.03 vs. 0.2 ± 0.03, P = 0.01) and right atria (0.33 ± 0.04 vs. 0.23 ± 0.02, P = 0.02). MRI analysis demonstrated increased ECV values in persistent AF (0.19 vs 0.34, paroxysmal vs persistent, P = 0.05). Tissue sections from the atria showed increase in fibrosis in pigs with persistent AF compared to paroxysmal AF. Staining demonstrated decreased myocardial fiber alignment and loss of anisotropy in persistent AF tissue. Changes in tissue organization and fibrosis are observed in the porcine model of persistent AF. Alterations in frequency activity and organization index can be captured with high resolution using flexible electrode arrays.

Extracellular volume fraction determined by equilibrium contrast-enhanced computed tomography: correlation with histopathological findings in gastric cancer

PurposeTo assess the relationship between histopathological features of gastric cancer and the extracellular volume fraction (ECV) measured by preoperative equilibrium contrast-enhanced computed tomography (CECT).Materials and methodsThe study group consisted of 66 patients with surgically resected gastric adenocarcinoma who underwent preoperative multiphasic CECT. Tumor ECVs were calculated using region-of-interest measurements within the gastric cancer and aorta of each case on unenhanced and equilibrium-phase images. The relationship between the mean ECV values and clinicopathological parameters was examined by univariate analysis. Parameters showing a significant difference in the former test were further tested by linear regression and receiver operating characteristic (ROC) curve analyses.ResultsIn the univariate analysis, the values of venous invasion (p = 0.0487) and tumor infiltration (INF) pattern (p < 0.0001) were significantly correlated with the tumor ECV. INF was significantly correlated (β = 0.57, p < 0.0001) in the linear regression analysis. The tumor ECV showed better diagnostic accuracy for predicting INF (INFa/b vs INFc), and the area under the ROC curve value was 0.89.ConclusionTumor ECV determined by equilibrium CECT is significantly correlated with the pathological INF of gastric cancer.