Elevated Extracellular Volume Research Articles

Unveiling myocardial microstructure shifts: exploring the impact of diabetes in stable CAD patients through CMR T1 mapping

BackgroundThis study investigates myocardial structural changes in stable coronary artery disease (CAD) patients with type 2 diabetes (T2D) using cardiac magnetic resonance (CMR) strain and T1 mapping.MethodsA total of 155 stable CAD patients underwent CMR examination, including left ventricular (LV) morphology and function assessment, late gadolinium enhancement (LGE), and feature tracking (CMR-FT) for LV global longitudinal, circumferential, and radial strain. T1 mapping with extracellular volume (ECV) evaluation was also performed.ResultsAmong the enrolled patients, 67 had T2D. Diabetic patients exhibited impaired LV strain and higher ECV compared to non-diabetics. Multivariate analysis identified T2D as an independent predictor of increased ECV and decreased strain.ConclusionsCMR-based strain and T1 mapping highlighted impaired myocardial contractility, elevated ECV, and potential interstitial fibrosis in diabetic patients with stable CAD. This suggests a significant impact of diabetes on myocardial health beyond CAD, emphasizing the importance of a comprehensive assessment in these individuals.Trial registrationhttp://www.controlled-trials.com/ISRCTN09454308

Assessment of myocardial microvascular dysfunction in patients with different stages of diabetes mellitus: An adenosine stress perfusion cardiac magnetic resonance study

PurposeTo examine myocardial perfusion and T1 mapping indicesin individuals with type 2 diabetes mellitus (T2DM) at various stages of glycemic control and whether uncontrolled glycemic levels would worsen myocardial microvascular function. MethodCardiac magnetic resonance examinations were performed on 114 T2DM patients without obstructive coronary artery disease and 55 matched controls. Participants were further divided into four subgroups: Q1 (control); Q2 (prediabetes); Q3 (controlled T2DM) and Q4 (uncontrolled T2DM). The correlation between HbA1c levels and myocardial perfusion parameters was evaluated. ResultsMPRI was decreased in the Q4 group than in the Q3 group, with borderline significance (P = 0.065). Compared with the Q1 group, stress T1 reactivity (ΔT1) was significantly reduced in the Q3 and Q4 group (P = 0.004 and < 0.001, respectively), but elevated in the Q2 group (P = 0.018). Extracellular volume (ECV) was considerably higher in the Q2 group and gradually rose in the Q3 and Q4 groups as compared to the Q1 group (P = 0.011, 0.001, and 0.007, respectively). HbA1c correlated negatively with MPRI and stress ΔT1, but positively with ECV (β = -1.993, P < 0.001; β = -0.180, P < 0.001; and β = 0.127, P < 0.001, respectively). ConclusionsStress ΔT1 reduced in T2DM patients but rose in prediabetes patients. Diabetes-induced elevated ECV begins early in the prediabetic stage and persists throughout the disorder. Myocardial perfusion and T1 mapping at stress can be used to detect early signs of microvascular dysfunction and subclinical risk factors in T2DM patients.

Clinical characteristics of patients with high extracellular volume fraction evaluated by cardiac computed tomography for coronary artery evaluation.

This study aims to evaluate the distribution of extracellular volume fraction detected via computed tomography, clinical characteristics of high extracellular volume fraction detected via computed tomography, and the rate of incidental detection of cardiac amyloidosis in patients undergoing cardiac computed tomography for coronary artery evaluation. This study included 874 consecutive patients (mean age, 74.4 ± 7.1 years; men, 65%), comprising men aged ≥60 years and women aged ≥70 years, who had undergone cardiac computed tomography between January 2020 and September 2022. The mean extracellular volume fraction detected via computed tomography was 29.7 ± 5.2%, and 108 patients (12.4%) had an extracellular volume fraction detected via computed tomography of ≥35%. Older age (75.9 ± 8.2 years vs. 74.2 ± 6.9 years; P = 0.042), male sex (75.9% vs. 63.0%; P = 0.007), impaired left ventricular ejection fraction, increased high-sensitivity cardiac troponin T and B-type natriuretic peptide levels, and increased left ventricular thickness showed significant associations with an extracellular volume fraction detected via computed tomography of ≥35%. Cardiac amyloidosis was diagnosed incidentally in 15 patients based on an increase in extracellular volume fraction detected via computed tomography. The prevalence of cardiac amyloidosis was 1.7% (15/874) and 14.3% (15/105) in the entire study population and in patients with an extracellular volume fraction detected via computed tomography of ≥35%, respectively. An increase in the extracellular volume fraction detected via computed tomography was suggestive of cardiac amyloidosis. Elevated extracellular volume fraction detected via computed tomography, associated with elevated cardiac biomarker levels and myocardial structural changes, may lead to the incidental diagnosis of cardiac amyloidosis.

Subclinical myocardial involvement in a cohort of patients with antisynthetase syndrome.

There is an increasing interest in knowing whether patients with antisynthetase syndrome (ASSD) may have silent myocardial interstitial involvement. Mapping techniques in cardiac magnetic resonance (CMR) can detect subclinical myocardial involvement. The purpose of this study was to identify alterations in multiparametric CMR in ASSD patients without overt cardiac involvement. Patients diagnosed with ASSD underwent a CMR along with the standard clinical workup, investigation of specific and associated myositis antibodies, and high-resolution chest CT. The CMR protocol includes routine morphologic, functional, and late gadolinium enhancement sequences in standard cardiac planes, as well as native T1 and T2 mapping sequences and extracellular volume (ECV) calculation. Twenty-five patients were included in this study (56% women; median age 56.3 years). Three patients were considered in the acute phase at the time of inclusion. Eight patients (32%) showed pathological findings in CMR (6 stable disease, 2 acute phase). Elevated T1, T2 and ECV mapping values were found in 20% (5/25), 17% (4/25) and 24% (6/25) of the group, respectively. Two patients in the acute phase had increased values of both T2 and ECV. Subclinical myocardial involvement in ASSD is not rare (32%) although its clinical significance is uncertain. Myocardial oedema (T2) was the most frequent finding, followed by increased T1 and/or ECV values likely signalling interstitial fibrosis. Of note, patients in the acute phase showed elevated T2 values.

Liver T1 Mapping Derived From Cardiac Magnetic Resonance Imaging: A Potential Prognostic Marker in Idiopathic Dilated Cardiomyopathy.

Hepatic alterations are common aftereffects of heart failure (HF) and ventricular dysfunction. The prognostic value of liver injury markers derived from cardiac MRI studies in nonischemic dilated cardiomyopathy (DCM) patients is unclear. Evaluate the prognostic performance of liver injury markers derived from cardiac MRI studies in DCM patients. Prospective. Three hundred fifty-six consecutive DCM patients diagnosed according to ESC guidelines (age 48.7 ± 14.2 years, males 72.6%). Steady-state free precession, modified Look-Locker inversion recovery T1 mapping and phase sensitive inversion recovery late gadolinium enhancement (LGE) sequences at 3 T. Clinical characteristics, conventional MRI parameters (ventricular volumes, function, mass), native myocardial and liver T1, liver extracellular volume (ECV), and myocardial LGE presence were assessed. Patients were followed up for a median duration of 48.3 months (interquartile range 42.0-69.9 months). Primary endpoints included HF death, sudden cardiac death, heart transplantation, and HF readmission; secondary endpoints included HF death, sudden cardiac death, and heart transplantation. Models were developed to predict endpoints and the incremental value of including liver parameters assessed. Optimal cut-off value was determined using receiver operating characteristic curve and Youden method. Survival analysis was performed using Kaplan-Meier and Cox proportional hazard. Discriminative power of models was compared using net reclassification improvement and integrated discriminatory index. P value <0.05 was considered statistically significant. 47.2% patients reached primary endpoints; 25.8% patients reached secondary endpoints. Patients with elevated liver ECV (cut-off 34.4%) had significantly higher risk reaching primary and secondary endpoints. Cox regression showed liver ECV was an independent prognostic predictor, and showed independent prognostic value for primary endpoints and long-term HF readmission compared to conventional clinical and cardiac MRI parameters. Liver ECV is an independent prognostic predictor and may serve as an innovative approach for risk stratification for DCM. 1 TECHNICAL EFFICACY: Stage 2.

Prognostic value of left ventricular hypertrophy in patients with myocardial fibrosis by ECV mapping on cardiac MRI

Abstract Background Cardiovascular magnetic resonance (CMR) can noninvasively identify myocardial fibrosis using extracellular volume (ECV) mapping. In patients with elevated ECV, and without hypertrophic cardiomyopathy (HCM) or cardiac amyloidosis, the prognostic significant of mild-to-moderate left ventricular hypertrophy (LVH) has not been well established. Purpose To determine if the presence of mild to moderate LVH has an impact on major adverse cardiovascular outcomes (MACE) in patients with elevated ECV without HCM or cardiac amyloidosis. Methods This was a retrospective cohort study assessing a group of patients referred for CMR between July 2019 and January 2023 to Mount Sinai Morningside. Patients with ECV&amp;gt;30% and left ventricular wall thickness &amp;lt;1.6 cm (to exclude patients with the possible diagnosis of HCM or cardiac amyloidosis) were considered for inclusion. Those with an established diagnosis of HCM or cardiac amyloidosis were also excluded. The LVH group comprised of patients with mild-to-moderate LVH, defined as a maximum wall thickness of 1.2-1.5 cm. The control group included patients without LVH (wall thickness &amp;lt;1.2 cm). Patients were further stratified by ECV, using the median value for our sample, as "high ECV" (≥35%) or "low ECV" (&amp;lt;35%). The outcome of interest was time-to-first MACE (all-cause death, or incident acute coronary syndrome, acute heart failure, or arrhythmia). Time-to-first MACE within 1 year was compared among groups using unadjusted Kaplan-Meier curves. Additional Cox regression analyses were performed to adjust for significant univariate analysis, including hypertension, hyperlipidemia, diabetes mellitus, use of beta-blocker, use of diuretic, and category of glomerular filtration rate. The results are presented as hazard ratios and 95% confidence intervals. All analyses were performed in SAS Enterprise using α&amp;lt;0.05. Results Out of the cohort, we identified 186 patients that met our selection criteria. The mean age was 61.1 ± 15.5 years, and 58.1% of patients were female. The median follow-up was 175 days in the control group and 115 days in the LVH group. There were 61 MACE (32.8%) in our sample. After adjusting for covariates, mild-to-moderate LVH was associated with 2.2 times the risk of MACE (95%CI 1.3 to 3.8; p=0.0047) at 1 year, compared to patients without LVH. A higher ECV (≥35%) was not significantly associated with worse outcomes within each study arm (p=0.3450). Kaplan Meier survival curves for patients with and without LVH are shown in Figure 1 (p=0.0002). Conclusions In patients with evidence of elevated ECV without underlying cardiac amyloidosis or hypertrophic cardiomyopathy, mild-to-moderate LVH is associated with 2.2 times the risk of MACE compared to normal left ventricular wall thickness.Figure 1

Prognosis prediction in cardiac amyloidosis by cardiac magnetic resonance imaging: a systematic review with meta-analysis.

Cardiac involvement is the foremost determinant of the clinical progression of amyloidosis. The diagnostic role of cardiac magnetic resonance (CMR) imaging in cardiac amyloidosis has been established, but the prognostic role of various right and left CMR tissue characterization and functional parameters, including global longitudinal strain (GLS), late gadolinium enhancement (LGE), and parametric mapping, is yet to be delineated. We searched EMBASE, PubMed, and MEDLINE for studies analysing the prognostic use of CMR imaging in patients with light chain amyloidosis or transthyretin amyloidosis cardiac amyloidosis. The primary endpoint was all-cause mortality. A random effects model was used to calculate a pooled odds ratio using inverse-variance weighting. Nineteen studies with 2199 patients [66% males, median age 59.7 years, interquartile range (IQR) 58-67] were included. Median follow-up was 24 months (IQR 20-32), during which 40.8% of patients died. Both tissue characterization left heart parameters such as elevated extracellular volume [hazard ratio (HR) 3.95, 95% confidence interval (CI) 3.01-5.17], extension of left ventricular (LV) LGE (HR 2.69, 95% CI 2.07-3.49) elevated native T1 (HR 2.19, 95% CI 1.12-4.28), and functional parameters such as reduced LV GLS (HR 1.91, 95% CI 1.52-2.41) and reduced LV ejection fraction (EF; HR 1.20, 95% CI 1.17-1.23) were associated with increased all-cause mortality. Unlike the presence of right ventricular (RV) LGE (HR 3.40, 95% CI 0.51-22.54), parameters such as RV GLS (HR 2.08, 95% CI 1.6-2.69), RVEF (HR 1.13, 95% CI 1.05-1.22), and tricuspid annular systolic excursion (TAPSE) (HR 1.11, 95% CI 1.02-1.21) were also associated with mortality. In this large meta-analysis of patients with cardiac amyloidosis, CMR parameters assessing RV and LV function and tissue characterization were associated with an increased risk of mortality.

Link between fibrosis-specific biomarkers and interstitial fibrosis in hypertrophic cardiomyopathy.

Cardiac fibrosis is a hallmark of hypertrophic cardiomyopathy (HCM) and has proven unfavorable clinical significance. Replacement fibrosis is better known, and has already been studied on a larger scale, whereas interstitial fibrosis is less explored. We aimed to analyze relationship between serum biomarkers and interstitial fibrosis, as assessed with cardiac magnetic resonance (CMR) in HCM. We performed 3T CMR scans in 50 HCM patients to assess interstitial fibrosis as expressed by extracellular volume (ECV). In all patients, we determined levels of serum cardiac-specific (troponin T [TnT], N-terminal prohormone of brain natriuretic peptide [NT-proBNP]) and fibrosis-specific (procollagen I C-terminal propeptide, procollagen III N-terminal propeptide, transforming growth factor β1, galectin 3) biomarkers. Patients were divided based on their median value of ECV. The final study population consisted of 49 patients. The median value of ECV in our cohort was 28.1%. Patients stratified according to median ECV differed in terms of several variables: body mass index, late gadolinium extent, NT-proBNP and galectin 3 levels (all P < 0.05). Cardiac biomarkers (TnT and NT-proBNP) and galectin 3 were significantly correlated with ECV (rS = 0.34; P = 0.02; rS = 0.39; P = 0.006; rS = 0.43; P = 0.002, respectively). Galectin 3 and body mass index were found to be independent predictors of ECV (odds ratio [OR], 2.29 [1.07-4.91]; P = 0.03; OR, 0.81 [0.68-0.97]; P = 0.02, respectively). Galectin 3 was an independent predictor of interstitial fibrosis in HCM patients expressed as elevated ECV values. The other fibrosis-specific biomarkers measured were not useful in detecting interstitial fibrosis in HCM. In addition, there was a positive correlation between classical cardiac biomarkers and interstitial fibrosis in HCM patients.

Imaging characterization of myocardial function, fibrosis, and perfusion in a nonhuman primate model with heart failure-like features.

The availability of a human-like chronic heart failure (HF) animal model was critical for affiliating development of novel therapeutic drug treatments. With the close physiology relatedness to humans, the non-human primate (NHP) HF model would be valuable to better understand the pathophysiology and pharmacology of HF. The purpose of this work was to present preliminary cardiac image findings using echocardiography and cardiovascular magnetic resonance (CMR) in a HF-like cynomolgus macaque model. The NHP diet-induced model developed cardiac phenotypes that exhibited diastolic dysfunction with reduced left ventricular ejection fraction (LVEF) or preserved LVEF. Twenty cynomolgus monkeys with cardiac dysfunction were selected by echocardiography and subsequently separated into two groups, LVEF < 65% (termed as HFrEF, n = 10) and LVEF ≥ 65% with diastolic dysfunction (termed as HFpEF, n = 10). Another group of ten healthy monkeys was used as the healthy control. All monkeys underwent a CMR study to measure global longitudinal strain (GLS), myocardial extracellular volume (ECV), and late gadolinium enhancement (LGE). In healthy controls and HFpEF group, quantitative perfusion imaging scans at rest and under dobutamine stress were performed and myocardial perfusion reserve (MPR) was subsequently obtained. No LGE was observed in any monkey. Monkeys with HF-like features were significantly older, compared to the healthy control group. There were significant differences among the three groups in ECV (20.79 ± 3.65% in healthy controls; 27.06 ± 3.37% in HFpEF group, and 31.11 ± 4.50% in HFrEFgroup, p < 0.001), as well as for stress perfusion (2.40 ± 0.34 ml/min/g in healthy controls vs. 1.28 ± 0.24 ml/min/g in HFpEF group, p < 0.01) and corresponding MPR (1.83 ± 0.3 vs. 1.35 ± 0.29, p < 0.01). After adjusting for age, ECV (p = 0.01) and MPR (p = 0.048) still showed significant differences among the three groups. Our preliminary imaging findings demonstrated cardiac dysfunction, elevated ECV, and/or reduced MPR in this HF-like NHP model. This pilot study laid the foundation for further mechanistic research and the development of a drug testing platform for distinct HF pathophysiology.

Cardiac magnetic resonance imaging T1 mapping and late gadolinium enhancement entropy: Prognostic value in patients with systemic sclerosis

BackgroundSystemic sclerosis (SSc) affects the myocardium, thereby resulting in a poor prognosis. Late gadolinium enhancement (LGE) entropy, derived from routine cardiac magnetic resonance (CMR) LGE images, is an index that reflects the complexity of the left ventricular myocardium. The aim of this study was to investigate whether LGE entropy can serve as a prognostic factor in patients with SSc. MethodsTwenty-four patients with SSc, who underwent CMR-T1 mapping and LGE to identify myocardial damage, were enrolled, and LGE entropy was measured. Extracellular volume (ECV) values were calculated using the same CMR-LGE images. The endpoint was major adverse cardiac events (MACEs), comprising all-cause death, hospitalization due to heart failure, and the onset of sustained ventricular tachycardia and ventricular fibrillation. The ability to predict MACE was assessed using receiver operating characteristic (ROC) analysis, and the predictability of LGE entropy was analyzed using Kaplan–Meier analysis. ResultsThe ROC curve analysis demonstrated a cut-off value of 7.39 for MACE with LGE entropy and had a sensitivity and specificity of 80 % and 79 %, respectively. Patients with LGE entropy ≥7.39 had a significantly higher MACE rate than those with LGE entropy <7.39 (p = 0.010). Moreover, LGE entropy ≥7.39 was a poor prognostic factor in patients without elevated ECV values. ConclusionsLGE entropy can be used to predict MACE and allows for further risk stratification in addition to ECV determination.

Cardiac Magnetic Resonance Imaging of COVID-19-Associated Cardiac Sequelae: A Systematic Review.

Many COVID-19 survivors experience persistent COVID-19 related cardiac abnormalities weeks to months after recovery from acute SARS-CoV-2 infection. Non-invasive cardiac magnetic resonance (CMR) imaging is an important tool of choice for clinical diagnosis of cardiac dysfunctions. In this systematic review, we analyzed the CMR findings and biomarkers of COVID-19 related cardiac sequela after SARS-CoV-2 infection. Following the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA), we conducted a systematic review of studies that assessed COVID-19 related cardiac abnormalities using cardiovascular magnetic resonance imaging. A total of 21 cross-sectional, case-control, and cohort studies were included in the analyses. Ten studies reported CMR results 3 months after SARS-CoV-2 infection and 11 studies 3 months after SARS-CoV-2 infection. Abnormal T1, abnormal T2, elevated extracellular volume, late gadolinium enhancement and myocarditis was reported less frequently in the 3-month studies. Eight studies reported an association between biomarkers and CMR findings. Elevated troponin was associated with CMR pathology in 5/6 studies, C-reactive protein in 3/5 studies, N-terminal pro-brain natriuretic peptide in 1/2 studies, and lactate dehydrogenase and D-dimer in a single study. The rate of myocarditis via CMR was 18% (154/868) across all studies. Most SARS-CoV-2 associated CMR abnormalities resolved over time. There were CMR abnormalities associated with SARS-CoV-2 infection and most abnormalities resolved over time. A panel of cardiac injury and inflammatory biomarkers could be useful in identifying patients who are likely to present with abnormal CMR pathology after COVID-19. Multiple mechanisms are likely responsible for COVID-19 induced cardiac abnormalities.

Abstract 10573: Left Ventricular Structure, Function, and Clinical Outcomes in Methamphetamine-Associated Heart Failure

Introduction: Methamphetamine use and overdose deaths are increasing. People who use methamphetamine are at risk for methamphetamine-associated heart failure (meth-HF). Cardiac fibrosis has been reported in nonischemic cardiomyopathies, but the role of cardiac fibrosis and other factors underlying the pathophysiology and reversibility of meth-HF remain unknown. Methods: Participants with meth-HF were recruited into a prospective cohort at a safety net hospital in San Francisco. Data collection included medical history, clinical outcomes, longitudinal echocardiograms (TTEs), markers of inflammation and fibrosis, and cardiac magnetic resonance imaging (CMR). Outcomes included mortality, changes in LVEF, and hospital readmission. Results: Forty-six participants enrolled: median age 51 years, 83% male, 41% Black, 20% Asian, 33% unstably housed, 76% actively using methamphetamine. Baseline TTEs demonstrated LV dilation (median LVIDd 5.7cm, LVIDs 4.7cm) and severely reduced LV systolic function (LVEF&lt;30% in 62%). After median 9 months follow-up, 13% were deceased. Compared to survivors, baseline LV dimensions were larger (mean LVIDd 6.7 vs 5.5cm, p&lt;0.05; LVIDs 6.1 vs 4.5cm, p&lt;0.05) and LVEF was lower (mean 19% vs 29%, p&lt;0.05) among those who died. At baseline, smaller LV size, higher LVEF, and guideline-directed medical therapy (GDMT) were more common in those with LVEF improvement &gt;10% (Fig). CMRs were often abnormal with late gadolinium enhancement and elevated extracellular volume, but there was no clear association with LV recovery. Conclusions: Despite their young age, the meth-HF population has a high mortality rate and severely reduced LVEF with LV dilation. Smaller LV size, higher LVEF, and GDMT were more common in those with LVEF improvement. These findings suggest that early identification and treatment of heart failure in people who use methamphetamine, along with drug cessation, may be associated with reversibility and improved outcomes.

Abstract 12257: Prognostic Value of Liver T1 Mapping and Extracellular Volume in Dilated Cardiomyopathy

Introduction: Cardiac dysfunction closely correlates with liver congestion and effect on liver relaxation time. Liver relaxometry could provide potential prognostic improvement for dilated cardiomyopathy (DCM) patients. Hypothesis: Liver relaxometry might have prognostic significance for DCM patients. Methods: We prospectively enrolled 433 patients diagnosed with DCM. Cardiac and hepatic T1, T2, and extracellular volume (ECV) were measured on the mid-ventricular mappings. The primary endpoint was defined as heart failure death, sudden cardiac death, and heart transplantation. Results: DCM patients who reached primary endpoint showed significantly increased liver native T1 (770.5±103.2ms versus 813.8±137.0ms, p=0.014) and ECV values (30.9±6.8% versus 34.3±10.7%, p=0.009) and decreased liver T2 value (35.8±5.5 versus 34.1±6.2ms, p=0.038). Right ventricular ejection fraction correlated moderately but significantly with liver native T1 (r =-0.293) and ECV (r=-0.245) (both p&lt;0.001). During the follow-up period (median duration 3.9 years) 97 patients reached the primary endpoint. In the Kaplan-Meier survival analysis, DCM patients with elevated liver native T1 or ECV had higher risk of reaching the primary endpoint (cutoff value: 854.9ms, p=0.001 and cutoff value: 34.5%, p&lt;0.001, respectively). Cox analysis indicated that liver ECV was an independent prognostic factor (hazard ratio:1.042, p&lt;0.001) and showed incremental prognostic value to age, sex, NYHA class III-IV, and LVEF. Conclusions: Liver native T1 and ECV correlates with cardiac magnetic resonance parameters. Furthermore, Liver ECV provides incremental prognostic value in DCM patients.

Myocardial extracellular volume is a non-invasive tissue marker of heart failure in patients with transposition of the great arteries and systemic right ventricle.

Focal myocardial fibrosis in the systemic right ventricle (RV) is related to ventricular dysfunction and adverse outcome in patients with d-transposition of the great arteries (dTGA) post atrial redirection and those with congenitally corrected TGA (ccTGA). The role of diffuse fibrotic lesions in these conditions remains poorly understood. Our study aimed to investigate diffuse myocardial fibrosis by measuring extracellular volume (ECV) with cardiovascular magnetic resonance (CMR) and to explore correlations between ECV and clinical as well as functional markers of heart failure in patients with TGA and systemic RV. We prospectively included dTGA and ccTGA patients aged ≥14 years and compared them to healthy controls. Standardized CMR included modified Look-Locker Inversion recovery T1 mapping to quantify diffuse myocardial fibrosis in the systemic RV and the subpulmonary left ventricle (LV). The centerline of RV and LV myocardium was marked with a line of interest tool to determine native and post-contrast T1 for quantification of ECV. In total, 13 patients (dTGA: n = 8, ccTGA: n = 5) with a median age of 30.3 years were enrolled. LV ECV was higher in patients than in controls [34% (30%-41%) vs. 26% (23%-27%), p < 0.001], with values increased above the upper limit of normal in 10/13 patients (77%). RV ECV tended to be higher in patients than in controls, albeit without statistical significance [29% (27%-32%) vs. 28% (26%-29%), p = 0.316]. Patients with elevated LV ECV had lower LV ejection fraction than those with normal ECV (52 ± 5% vs. 65 ± 4%, p = 0.007). Correlations with clinical parameters were not observed. LV ECV was significantly higher than RV ECV (p = 0.016) in the patient group. In this study, LV ECV was significantly increased in TGA patients compared to controls, and was associated with LV dysfunction. Our data suggest that ECV may serve as a non-invasive tissue marker of heart failure in TGA with systemic RV. Further research is necessary to evaluate the prognostic implications and the potential role of ECV in monitoring disease progression and guiding therapy, aiming to maintain LV function or train the LV for subaortic location in TGA patients from infancy to adulthood.

Early detection of myocardial fibrosis in cardiomyopathy in the absence of late enhancement: role of T1 mapping and extracellular volume analysis.

To analyze myocardial fibrosis in dilated cardiomyopathy (DCM) patients with no late gadolinium enhancement (LGE) on cardiac magnetic resonance (CMR) using T1 mapping and extracellular volume (ECV) and investigate the potential correlation with left ventricular (LV) dilation and dysfunction. The study included 41 DCM patients without LGE and 79 healthy controls. T1 and ECV were compared between the two groups using multivariable logistic regression analysis. The correlations between histological and functional parameters were evaluated using Pearson's correlation. Mean native myocardial T1 and ECV were significantly higher in the DCM group compared to controls (p ≤ 0.001, respectively). Multivariable logistic regression revealed that ECV (mean, minimum), LV ejection fraction (LVEF), and LV end-diastolic diameter (LVEDD) were independent discriminators for LGE-negative DCM; the area under the curve (AUC) of LVEF, LVEDD, ECV mean, and ECV minimum were 0.97, 0.96, 0.88, and 0.68, respectively. In the DCM group, LVEDD and LVEF were positively and negatively correlated with ECV, respectively. LVEDV index and LV end-systolic volume (LVESV) index were positively correlated with native-T1 and ECV, and the absolute value of LV global strain had a negative correlation with ECV. Early myocardial fibrosis in DCM could be detected by prolonged native T1 and elevated ECV despite the absence of LGE on CMR. Moreover, the change of histological characteristics of myocardium in DCM was correlated with LV dilation and dysfunction. • At an early stage, patients with DCM may have myocardial fibrosis despite the absence of LGE. • T1 mapping and ECV are efficient methods for early detection of potential myocardial fibrosis. • Increased native T1 and ECV are correlated with left ventricular dilation and dysfunction in LGE-negative DCM patients.

Myocardium Assessment by Relaxation along Fictitious Field, Extracellular Volume, Feature Tracking, and Myocardial Strain in Hypertensive Patients with Left Ventricular Hypertrophy.

Background Previous research has shown impaired global longitudinal strain (GLS) and slightly elevated extracellular volume fraction (ECV) in hypertensive patients with left ventricular hypertrophy (HTN LVH). Up to now, only little attention has been paid to interactions between macromolecules and free water in hypertrophied myocardium. Purpose To evaluate the feasibility of relaxation along a fictitious field with rank 2 (RAFF2) in HTN LVH patients. Study Type. Single institutional case control. Subjects 9 HTN LVH (age, 69 ± 10 years) and 11 control subjects (age, 54 ± 12 years). Field Strength/Sequence. Relaxation time mapping (T1, T1ρ, and TRAFF2 with 11.8 μT maximum radio frequency field amplitude) was performed at 1.5 T using a Siemens Aera (Erlangen, Germany) scanner equipped with an 18-channel body array coil. Assessment. ECV was calculated using pre- and postcontrast T1, and global strains parameters were assessed by Segment CMR (Medviso AB Co, Sweden). The parametric maps of T1ρ and TRAFF2 were computed using a monoexponential model, while the Bloch-McConnell equations were solved numerically to model effect of the chemical exchange during radio frequency pulses. Statistical Tests. Parametric maps were averaged over myocardium for each subject to be used in statistical analysis. Kolmogorov-Smirnov was used as the normality test followed by Student's t-test and Pearson's correlation to determine the difference between the HTN LVH patients and controls along with Hedges' g effect size and the association between variables, respectively. Results T RAFF2 decreased statistically (83 ± 2 ms vs 88 ± 6 ms, P < 0.031), and global longitudinal strain was impaired (GLS, −14 ± 3 vs − 18 ± 2, P < 0.002) in HTN LVH patients compared to the controls, respectively. Also, significant negative correlation was found between TRAFF2 and GLS (r = −0.53, P < 0.05). Data Conclusion. Our results suggest that TRAFF2 decrease in HTN LVH patients may be explained by gradual collagen accumulation which can be reflected in GLS changes. Most likely, it increases the water proton interactions and consequently decreases TRAFF2 before myocardial scarring.

Sex Differences in Type 2 Diabetes Mellitus-Related Left Ventricular Remodeling: A Cardiovascular Magnetic Resonance Study.

Background The purpose of this study was to evaluate the sex differences in myocardial structure, tissue characteristics, and myocardial function in type 2 diabetes mellitus (T2DM) patients. Methods A total of 62 T2DM patients and 40 controls were prospectively recruited for the study. All the participants were scanned using cardiovascular magnetic resonance (CMR) cine and underwent native and postcontrast T1 mapping to obtain left ventricular (LV) structure, function, and tissue characteristics. The differences between the control and T2DM patients were compared in males and females, respectively. Results For myocardial structure, T2DM was associated with a larger ratio of myocardial mass to end-diastolic volume (MVR, T2DM: 0.87 ± 0.20 vs. controls: 0.73 ± 0.14, p = 0.008) and thicker wall thickness (WT, T2DM: 6.5 ± 1.1 mm vs. controls: 5.6 ± 1.0 mm, p = 0.002) in females. For tissue characteristics, T2DM was associated with a similar T1 value, elevated extracellular volume fraction (ECV, T2DM: 27.8 ± 3.6% vs. controls: 25.1 ± 2.5%, p = 0.002), and increased extracellular matrix volume index (ECMVi, T2DM: 15.8 ± 3.8 ml/m2 vs. controls: 13.4 ± 2.7 ml/m2, p = 0.008) in males. For myocardial function, in male, compared with control, T2DM was associated with decreased peak longitudinal diastolic strain rate (PLDSR, T2DM: 0.97 ± 0.19 1/s vs. control: 1.13 ± 0.29 1/s, p = 0.030). Conclusions There might be sex differences in myocardial remodeling induced by T2DM, including LV structural concentric remodeling in female patients and extracellular matrix remodeling and subclinical diastolic dysfunction in male patients.

A Radiomic MRI based Nomogram for Prediction of Heart Failure with Preserved Ejection Fraction in Systemic Lupus Erythematosus Patients: Insights From a Three-Center Prospective Study.

Myocardial T1 and extracellular volume (ECV) fraction values have important roles in the prognostication of heart failure with preserved ejection fraction (HFpEF). However, the traditional mean quantification of intensity levels is not sufficient. To evaluate a T1 map-based radiomic nomogram as a long-term prognosticator for HFpEF in systemic lupus erythematosus (SLE) patients. Prospective. A total of 115 SLE patients and 50 age- and gender-matched controls. A 3.0T scanner; cine imaging, precontrast and post-contrast T1 mapping and T2 mapping sequences. A radiomic nomogram was developed based on precontrast T1 mapping. Three independent readers assessed and compared the ECV value and the value of the radiomic nomogram for predicting HFpEF in SLE patients. Cox proportional hazard models, Youden index for determining cut-off values for high HFpEF risk vs. low HFpEF risk classification, Kaplan-Meier analysis, intraclass correlation (ICC), and Uno C statistic test. During a median follow-up of 27 (interquartile range, 19-37) months, 31 SLE patients developed HFpEF. Patients with elevated ECV (≥31%) and a higher output (≥42.7) from the radiomic feature "S_33_sum average" of the precontrast T1 map had a significantly higher risk of developing HFpEF than those who had lower ECV (<31%) and an output <42.7. Patients with a higher "S_33_sum average" value on precontrast T1 map had a significantly increased risk for HFpEF (hazard ratio, 1.363, 95% CI, 1.130-1.645), after adjusting for covariates including ECV and LVEF. Finally, "S_33_sum average" from precontrast T1 mapping had modest but significantly incremental prognostic value over the mean ECV value (Uno C statistic comparing models, 0.860 vs. 0.835). The precontrast T1 map-based radiomic nomogram, as a measure of diffuse myocardial fibrosis was associated with HFpEF and provided modest prognostic value for predicting HFpEF in SLE patients. 1 TECHNICAL EFFICACY: Stage 2.

Combined simultaneous FDG-PET/MRI with T1 and T2 mapping as an imaging biomarker for the diagnosis and prognosis of suspected cardiac sarcoidosis

PurposeTo evaluate the diagnostic and prognostic significance of combined cardiac 18F-fluorodeoxyglucose (FDG) PET/MRI with T1/T2 mapping in the evaluation of suspected cardiac sarcoidosis.MethodsPatients with suspected cardiac sarcoidosis were prospectively enrolled for cardiac 18F-FDG PET/MRI, including late gadolinium enhancement (LGE) and T1/T2 mapping with calculation of extracellular volume (ECV). The final diagnosis of cardiac sarcoidosis was established using modified JMHW guidelines. Major adverse cardiac events (MACE) were assessed as a composite of cardiovascular death, ventricular tachyarrhythmia, bradyarrhythmia, cardiac transplantation or heart failure. Statistical analysis included Cox proportional hazard models.ResultsForty-two patients (53 ± 13 years, 67% male) were evaluated, 13 (31%) with a final diagnosis of cardiac sarcoidosis. Among patients with cardiac sarcoidosis, 100% of patients had at least one abnormality on PET/MRI: FDG uptake in 69%, LGE in 100%, elevated T1 and ECV in 100%, and elevated T2 in 46%. FDG uptake co-localized with LGE in 69% of patients with cardiac sarcoidosis compared to 24% of those without, p = 0.014. Diagnostic specificity for cardiac sarcoidosis was highest for FDG uptake (69%), elevated T2 (79%), and FDG uptake co-localizing with LGE (76%). Diagnostic sensitivity was highest for LGE, elevated T1 and ECV (100%). After median follow-up duration of 634 days, 13 patients experienced MACE. All patients who experienced MACE had LGE, elevated T1 and elevated ECV. FDG uptake (HR 14.7, p = 0.002), elevated T2 (HR 9.0, p = 0.002) and native T1 (HR 1.1 per 10 ms increase, p = 0.044) were significant predictors of MACE even after adjusting for left ventricular ejection fraction and immune suppression treatment. The presence of FDG uptake co-localizing with LGE had the highest diagnostic performance overall (AUC 0.73) and was the best predictor of MACE based on model goodness of fit (HR 14.9, p = 0.001).ConclusionsCombined cardiac FDG-PET/MRI with T1/T2 mapping provides complementary diagnostic information and predicts MACE in patients with suspected cardiac sarcoidosis.

Diffuse myocardial fibrosis by T1 mapping is associated with heart failure in pediatric primary dilated cardiomyopathy

BackgroundIn adult cardiomyopathy (CM), diffuse myocardial fibrosis is associated with adverse clinical outcome. However, its relevance in pediatric patients remains relatively unknown. The study aimed to evaluate myocardial extracellular volume (ECV) reflecting diffuse myocardial fibrosis with cardiovascular magnetic resonance (CMR) T1 mapping, and to analyze correlations with clinical and functional data in children and adolescents with different CM phenotypes. MethodsPatients with primary dilated (DCM), hypertrophic (HCM) or left ventricular non-compaction CM (LVNC) were prospectively enrolled and compared with healthy controls. Study participants underwent standardized CMR with modified Look-Locker Inversion recovery (MOLLI) T1 mapping. ResultsIn total, 33 patients (median age 12.0 years; DCM: n = 10, HCM: n = 13; LVNC: n = 10) and 7 controls (14.5 years) were included.DCM: ECV was higher than in controls (38.1 ± 7.5% vs. 27.2 ± 3.6%; p = 0.014). Patients with elevated ECV were younger than those with normal values (p = 0.044). ECV correlated with N-terminal pro brain natriuretic peptide (r = 0.66, p = 0.038), left ventricular ejection fraction (r = −0.63, p = 0.053), and stroke volume of left (r = −0.75, p = 0.013) and right ventricle (r = −0.67, p = 0.033). During a median follow-up of 25.3 months, 3 patients underwent heart transplantation (HTx), and 2 were listed for HTx. All 5 patients had elevated ECV.HCM/LVNC: ECV was within normal range in HCM (25.5 ± 4.5%) and LVNC (29.6 ± 4.2), and was not related with clinical and/or functional parameters. ConclusionsOur results indicate an increased burden of diffuse myocardial fibrosis in relation with younger age in pediatric DCM. ECV was associated with clinical and biventricular functional markers of heart failure in DCM.