Higher Extracellular Volume Research Articles

Regional distribution of diffuse fibrosis in the basal and mid-ventricular AHA segments in patients with type 2 diabetes

Abstract Introduction Cardiovascular magnetic resonance (CMR) research including from our research group, has documented that patients (pts.) with type 2 diabetes (DM2) even without symptoms exhibit subtle to moderately increased myocardial extracellular volume (ECV). ECV is an imaging biomarker of diffuse fibrosis. Also, our prior research has revealed a prevalence of approx. 10% for non-ischemic late gadolinium enhancement (LGE). Intriguingly, these LGE lesions manifested in a distinct pattern, situated in the basal lateral or infero-lateral positions. We postulate that these lesions may represent the end-stage of severe diffuse fibrosis, potentially influenced by factors such as increased shear wall stress. Purpose To investigate if pts. with DM2 with known high global ECV had higher regional ECV in the basal and lateral or infero-lateral AHA segments compared to other segments. Method A case-control study of 20 healthy controls, 20 pts. with DM2 with low ECV (ECV<28%), 20 pts. with DM2 with high ECV (ECV>29%), and 20 pts. with DM2 with non-ischemic LGE (LGE+). Pts. were identified from a cross-sectional cohort of pts. with DM2. All subjects underwent physical examination and extensive CMR with T1 mapping before and after gadolinium contrast, and myocardial perfusion at rest and during adenosine stress. The regional ECV values for the basal and the mid-ventricular short axis slide were analysed using the AHA segments model: segments 1 to 12. Results All groups (grp.) had comparable age and sex distribution. In the DM2 grp. there was a difference between the no. of pts. with DM2 duration >10 years (low ECV 11(55%), high ECV 12(60%), LGE+ 16(80%), however statistically significant. Global ECV were: Controls (mean±sd) 26.7±1.6%, Low ECV 26.3±1.4%, High ECV 32.0±2.9%, LGE+ 29.5±2.6%, p<0.001. Control subjects had regional ECV between 24.4±2% to 27.3±2% (p<0.001), highest values in the septum. The DM2 grp. with low ECV had regional ECV values of 24.5±3% to 29.2±4%, highest values in the basal inferior and septal parts (segments 2-4). The high ECV grp. had regional ECV values between 28.3±4% and 35.3±6 % with very high values in the basal and the mid-ventricular septum, inferior, and inferolateral part (segments 2-5 and 8-11). The DM2 group LGE+ had values between 26.6±3% and 34.5±7%, highest values in the basal slice in the septum, inferior, and infero-lateral parts (segments 2-5). We found no significant difference in the regional myocardial perfusion reserve index. Conclusion This evidence indicates that diffuse fibrosis in DM2 cardiomyopathy tends to concentrate in the septum and inferolateral regions. However, among pts. with non-ischemic LGE lesions, we observed normal ECV in the anterior segments, in contrast to the high ECV group where all segments exceeded normal levels, albeit with notable regional variations. Subsequent investigations should prioritize uncovering the underlying reasons for this specific regional distribution of diffuse fibrosis.AHA segments 1-12 mapsAHA segments 1-12 maps

Relationships between 18-month kinetics and functional capacity and left ventricular remodeling and cardiac fibrosis in dilated cardiomyopathy

Abstract Introduction Myocardial fibrosis is a primary pathogenetic process in dilated cardiomyopathy (DCM) that is responsible for progressive cardiac remodeling and functional capacity impairment. We sought to verify whether there were differences between 18-month kinetics of functional capacity and left ventricular remodeling in DCM patients with different types and advancement of fibrosis who were up-titrated with guideline directed pharmacotherapy (GDMT). Methods Between May 2019 and September 2020, 99 DCM patients (88 male, mean age 45.2 ± 11.8 years, mean EF 29.7 ± 10%) underwent cardiac magnetic resonance with assessment of replacement fibrosis via late gadolinium enhancement (LGE) and interstitial fibrosis via extracellular volume (ECV). Each patient had serial (baseline, 6-, 12-, 18 month) functional assessment: NYHA class and 6- minute walking test (6-MWT) and follow-up echocardiography, including measurement of left ventricular end-diastolic volume (LVEDvol) and ejection fraction (EF). Patients were divided into LGE-negative and LGE-positive groups, whereas based on median ECV – they were divided into those with ECV below and above median values. Results Overall, LGE was identified in 44 (44%) of patients, whereas median ECV was 27.7%. NYHA class was significantly worse in patients with LGE (1.5±0.5 vs. 1.9±0.6) and with higher ECV (1.93±0.6 vs. 1.6±0.5) in comparison to those without LGE and lower ECV. However, NYHA class improved during observational period in all groups. There were no differences in 6-MWT distance in LGE positive and negative groups at all time points. Baseline 6-MWT distance in LGE positive group was 494.2±88.2 vs. 453.9±98.8 meters in LGE negative group. Baseline 6-MWT distance in upper median ECV group was (408.8±103.5 vs. 492.4±92.9 meter) was significantly lower ECV group (p=0.03). During 18 months 6-MWT distance increased only in LGE negative group but in both ECV groups (Figure 1 A-D). There were no differences in EF between patients with and without LGE and also with higher and lower ECV. Baseline EF in LGE positive group was 27.4±11.2% and 31.7±10.6% in LGE negative. Baseline indexed LVEDvol in LGE positive group was 107.7±40.7 vs. 91.8±37.8 ml/m2 (p=0.09) in LGE negative group. EF increased significantly in both groups, whereas indexed LVEDvol decreased only in LGE negative group (Figure 2 A-D). Conclusions Regardless of the presence of replacement and to some extent of interstitial fibrosis, functional and cardiac morphological improvement was observed during 18 months observation in DCM patients on GDMT. The greatest improvement occurred during the first 3 (occasionally 6) months which was associated with the greatest escalation of GDMT. Further dose escalation was not associated with a significant improvement in both functional and morphological parameters.

Associate variables of coronary computed tomographic angiography-derived extracellular volume fraction and cardiac magnetic resonance-derived late-gadolinium enhancement

Abstract Background Coronary computed tomographic angiography (CCTA) with late-iodine enhancement enables the segmental quantification of extracellular volume (ECV) fraction which represents myocardial fibrosis. However, its association with cardiac magnetic resonance (CMR)-derived late gadolinium enhancement (LGE) has not been fully elucidated. Purpose We aimed to assess the concordance and discordance between CCTA-derived ECV and CMR-derived LGE and to investigate associated variables of each index. Methods This retrospective analysis included a total of 123 segments from 41 patients (anterior, inferior and lateral segments per patient) with known or suspected coronary artery disease (CAD) who underwent both clinically indicated CCTA and CMR. Patients with cardiomyopathy such as amyloidosis were excluded. Myocardial fibrosis was evaluated by CCTA-derived segmental ECV and by CMR-LGE with ischemic pattern on a per-segment basis (AHA 16 segments). Clinical and echocardiographic variables associated with CCTA-derived segmental ECV and CMR-LGE were studied by univariable linear and logistic regression analyses, respectively. Results Among the 123 segments, 21 segments showed ischemic CMR-LGE pattern. CCTA-ECV was significantly higher in segments with versus without CMR-LGE (42 [39, 47] % versus 34 [29, 39] %, P<0.01). Receiver-operating characteristic curve analysis showed that the best cut-off of CCTA-ECV to predict CMR-LGE was 38.9% (area under the curve 0.82 [95% confidence interval 0.74, 0.90], positive predictive value: 40.0%, negative predictive value: 96.2%). Univariable analyses revealed that male sex, prior history of revascularization, usage of statin, aspirin, angiotensin-converting enzyme inhibitor and beta-blockade, higher C-reactive protein, NT-pro BNP, lower left ventricular ejection fraction, greater left ventricular chamber size, shorter deceleration time, and larger segmental and global longitudinal strain were associated with both higher CCTA-ECV and the presence of CMR-LGE. Lower lipid profiles, higher high-sense troponin I, and greater left atrial volume index were associated with higher CCTA-ECV, while not with the presence of CMR-LGE. The frequency of CMR-LGE were significantly different according to CCTA-ECV tertiles. (P<0.05) Statin use and higher NT-proBNP were determinants of the highest ECV tertile without LGE. Conclusion We found a strong interrelationship between variables associated with ECV and the presence of LGE, although high ECV may not necessarily indicate the presence of LGE in patients with known or suspected CAD. Clinical factors associated with discordance, such as high-ECV without CMR-LGE, should be taken into account in the assessment of ECV and LGE. Further studies are needed to elucidate clinical significance of the concordance and discordance between ECV and LGE.

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.

Microvascular obstruction in cardiac amyloidosis.

Cardiac amyloidosis (CA) is characterized by deposition of amyloid fibrils within the extracellular space, causing disarray of the myocardial structure and capillary architecture. This study aims to characterize the prevalence of microvascular obstruction (MVO) in patients with CA and to assess the association between MVO and prognosis. The study population comprised 800 patients, of which 400 had light-chain CA (AL-CA) and 400 had transthyretin CA (ATTR-CA). MVO was present in 221 (27.6%) patients, and more common in ATTR-CA than AL-CA (124 [56.1%] vs. 97 [43.9%], p = 0.033). Patients with MVO had a more severe cardiac phenotype evidenced by higher N-terminal pro-brain natriuretic peptide (3516 ng/L [1944-6247] vs. 2508 ng/L [1203-5752], p < 0.001), worse global longitudinal strain (-10.5% [-12.6; -7.9] vs. -12.0% [-16.0; -8.9], p < 0.001), and higher extracellular volume (56% [51-61] vs. 50% [45-57], p < 0.001). Patients with AL-CA and MVO had a higher serum troponin (86 ng/L [47-148] vs. 59 ng/L [44-78], p < 0.001), and higher T2 (53 ms [50-56] vs. 50 ms [48-52], p < 0.001), but lower extracellular volume (55% [50-60] vs. 58% [53-61], p = 0.008) and lower indexed myocyte cell volume (48.6 g/m2 [41.1-59.8] vs. 55.7 g/m2 [47.5-68.4], p < 0.001) than patients with ATTR-CA and MVO. MVO was associated with an increased risk of mortality in the overall population (hazard ratio [HR] 1.28, 95% confidence interval [CI] 1.03-1.59, p = 0.025), and the subgroup with AL-CA (HR 1.59, 95% CI 1.17-2.17, p = 0.003) but not ATTR-CA (HR 1.04, 95% CI 0.77-1.40, p = 0.814). Microvascular obstruction is common in CA and is related to markers of amyloid infiltration. MVO is associated with an increased risk of mortality in AL-CA, but not in ATTR-CA. This reflects the intrinsic differences in disease biology between these two forms of CA, with MVO likely related to multiple myocardial processes, amyloid infiltration, oedema and myocyte death.

Multiparametric MRI Scoring System of the Pancreas for the Diagnosis of Chronic Pancreatitis.

Ductal features alone may not offer high diagnostic sensitivity or most accurate disease severity of chronic pancreatitis (CP). Diagnose CP based on multiparametric MRI and MRCP features. Prospective. Between February 2019 and May 2021, 46 control (23 males, 49.3 ± 14.1 years), 45 suspected (20 males, 48.7 ± 12.5 years), and 46 definite (20 males, 53.7 ± 14.6 years) CP patients were enrolled at seven hospitals enrolled in the MINIMAP study. CP classification was based on imaging findings and clinical presentation. 1.5 T. T1-weighted (T1W) spoiled gradient echo, T1 map with variable flip angle, dual-echo Dixon, secretin-enhanced MRCP before and after secretin infusion. Dual-echo fat fraction (FF), T1 relaxation time, extracellular volume (ECV), T1 signal intensity ratio of the pancreas to the spleen (T1 score), arterial-to-venous enhancement ratio (AVR), pancreatic tail diameter (PTD), pancreas volume, late gadolinium enhancement, pancreatic ductal elasticity (PDE), and duodenal filling grade of secretin-enhanced MRCP were measured. Logistic regression analysis generated CP-MRI and secretin-enhanced CP-SMRI scores. Receiver operating characteristics analysis was used to differentiate definite CP from control. Interobserver agreement was assessed using Lin's concordance correlation coefficient. Compared to control, definite CP cohort showed significantly higher dual-echo FF (7% vs. 11%), lower AVR (1.35 vs. 0.85), smaller PTD (2.5 cm vs. 1.95 cm), higher ECV (28% vs. 38%), and higher incidence of PDE loss (6.5% vs. 50%). With the cut-off of >2.5 CP-MRI score (dual-echo FF, AVR, and PTD) and CP-SMRI score (dual-echo FF, AVR, PTD, and PDE) had cross-validated area under the curves of 0.84 (sensitivity 87%, specificity 68%) and 0.86 (sensitivity 89%, specificity 67%), respectively. Interobserver agreement for both CP-MRI and CP-SMRI scores was 0.74. The CP-MRI and CP-SMRI scores yielded acceptable performance and interobserver agreement for the diagnosis of CP. 1 TECHNICAL EFFICACY: Stage 2.

The detrimental role of galectin-3 and endoplasmic reticulum stress in the cardiac consequences of myocardial ischemia in the context of obesity.

The association between cardiac fibrosis and galectin-3 was evaluated in patients with acute myocardial infarction (MI). The role of galectin-3 and its association with endoplasmic reticulum (ER) stress activation in the progression of cardiovascular fibrosis was also evaluated in obese-infarcted rats. The inhibitor of galectin-3 activity, modified citrus pectin (MCP; 100 mg/kg/day), and the inhibitor of the ER stress activation, 4-phenylbutyric acid (4-PBA; 500 mg/kg/day), were administered for 4 weeks after MI in obese rats. Overweight-obese patients who suffered a first MI showed higher circulating galectin-3 levels, higher extracellular volume, and LV infarcted size, as well as lower E/e'ratio and LVEF compared with normal-weight patients. A correlation was observed between galectin-3 levels and extracellular volume. Obese-infarcted animals presented cardiac hypertrophy and reduction in LVEF, and E/A ratio as compared with control animals. They also showed an increase in galectin-3 gene expression, as well as cardiac fibrosis and reduced autophagic flux. These alterations were associated with ER stress activation characterized by enhanced cardiac levels of binding immunoglobulin protein, which were correlated with those of galectin-3. Both MCP and 4-PBA not only reduced cardiac fibrosis, oxidative stress, galectin-3 levels, and ER stress activation, but also prevented cardiac functional alterations and ameliorated autophagic flux. These results show the relevant role of galectin-3 in the development of diffuse fibrosis associated with MI in the context of obesity in both the animal model and patients. Galectin-3 in tandem with ER stress activation could modulate different downstream mechanisms, including inflammation, oxidative stress, and autophagy.

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.

Systematic review of cardiovascular magnetic resonance imaging T1 and T2 mapping in patients with Takotsubo syndrome

BackgroundCurrent imaging advancements quantify the use of cardiovascular magnetic resonance (CMR) derived T1 and T2 tissue characterization as robust indicators for cardiomyopathies, but limited literature exists on its clinical application in Takotsubo syndrome (TTS). This systematic review evaluated the T1 and T2 parametric mapping to delineate the current diagnostic and prognostic CMR imaging outcomes in TTS. MethodsA comprehensive literature search until October 2023 was performed on ScienceDirect, PubMed, Web of Science, and Cochrane Library by two independent reviewers adhering to the PRISMA framework. The Newcastle-Ottawa Scale (NOS) was used to evaluate the methodological quality of studies. ResultsOut of 198 results, 8 studies were included in this qualitative synthesis, accounting for a total population of 399 subjects (TTS = 201, controls = 175, acute myocarditis = 14, and acute regional myocardial oedema without infarction = 9). Approximately 50.4 % were TTS patients aged between 61 and 73 years, whereof, females (n = 181, 90.0 %) and apical variants (n = 180, 89.6 %) were significantly higher, and emotional stressor (n = 42; 20.9 %) was more prevalent than physical (n = 27; 13.4 %). The NOS identified 62.5 % of studies as moderate and 37.5 % as high quality. Parametric tissue mapping revealed significantly prolonged T1 and T2 relaxation times at 1.5T and 3T respectively in TTS (1053–1164 msec, 1292–1438 msec; and 56–67 msec, 60–90 msec) with higher extracellular volume (ECV) fraction (29–36 %), compared to healthy subjects (944–1211 msec, 1189–1251 msec; and 46–54 msec, 32–68 msec; 23–29 %) and myocarditis (1058 msec, 60 msec). Other significant myocardial abnormalities included increased left ventricular (LV) end-systolic and diastolic volume and reduced global longitudinal strain. Overall, myocardial oedema, altered LV mass and strain, and worse LV systolic function, with higher native T1, T2, and ECV values were consistent. ConclusionsFuture research with substantially larger clinical trials is vital to explore the CMR imaging findings in diverse TTS patient cohorts and correlate the T1 and T2 mapping outcomes with demographic/clinical covariates. CMR is a valuable imaging tool for TTS diagnosis and prognostication. T1 and T2 parametric mapping facilitates the quantification of oedema, inflammation, and myocardial injury in Takotsubo.

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

Abstract 14282: Electrocardiography Rules out Myocardial Abnormalities on Cardiac Magnetic Resonance Imaging in Post-Hospitalized COVID-19 Patients: A Multicenter Observational Study

Introduction: The diagnostic performance of EKG in ruling out myocardial abnormalities following COVID-19 is unclear. Aim: To assess the ability of EKG to exclude cardiac abnormalities on cardiac magnetic resonance imaging (CMR) in post-hospitalised COVID-19 patients. Methods: Post-hospitalized patients (n=212) &amp; comorbidities matched controls (n=38) underwent CMR and 12-lead EKG. EKG assessments included depolarization &amp; repolarization abnormalities [ QTc , corrected QT dispersion ( QTc disp ), JT ( JTc ) &amp; T peak-end ( cTPe ) intervals]. CMR abnormalities were defined as reduced left ventricular ejection fraction (LVEF), high T1 &amp; T2 Z scores and high extracellular volume and pathological late gadolinium enhancement. Results: At 5.6 months post-discharge, patients had a higher burden of EKG abnormalities vs controls (72.2% vs 42.1%, p=0.001 ) (Figure A) . CMR abnormalities were comparable despite patients having lower LVEF. Abnormal EKG findings and prolonged repolarization were more common in patients with CMR abnormalities vs patients with normal CMR and controls ( Figure A &amp; B ). Area-under-the-receiver-operating curve (AUROC) of routine EKG abnormalities to discriminate abnormal CMR was 0.56 (95% CI 0.47-0.65), p=0.185. Inclusion of JTc &amp; QTc disp improved the AUROC to 0.64 (95% CI 0.55-0.74), p=0.002. Inclusion of JTc ≥340ms &amp; QTc disp ≥40ms improved the sensitivity from 81.6% to 99.9% with higher negative predictive value (84.7% to 99.9%) ( Figure A ). Conclusions: Post-hospitalized COVID-19 patients have more EKG abnormalities than comorbidities-matched controls. A normal EKG with normal repolarization is effective in ruling out significant CMR abnormalities.

Abstract 13751: Clinical Characteristics With High Extracellular Volume Fraction in Patients Who Performed Cardiac Computed Tomography Angiography for the Purpose of Evaluating Coronary Arteries

Background: Cardiac computed tomography angiography (CCTA) is useful for the evaluation of anatomical coronary artery lesions. Recently, extracellular volume fraction by computed tomography (ECV CT ) have become possible by imaging the delay phase after coronary CT angiography. ECV CT has been reported to be useful for detailed examination and prognosis prediction after therapeutic intervention of cardiomyopathy. Cardiac amyloidosis is known as a cardiomyopathy with noticeable increased ECV, and cardiac amyloidosis should be suspected in patients with high ECV. The aim of this study was to evaluate clinical characteristics of high ECV CT and incidental detection of cardiac amyloidosis in patients who underwent CCTA for the purpose of evaluation of coronary arteries. Methods and Results: We examined consecutive 875 patients (mean age; 74.3 ± 7.1 years, men; 64%) who underwent CCCA in men aged ≥ 60 years and women aged ≥ 70 years. ECV CT quantification was performed with pre-contrast and post-contrast delayed phase CT images with the subtraction-derived method. Mean ECV CT was 29.7 ± 5.2%, and a total of 109 patients (12.3%) had ECV CT ≥ 35%. The patients with ECV CT ≥ 35% were significantly older (75.8±8.1 years vs. 74.1±6.9 years; P=0.038) and male dominant 75.4% vs 63.1%; P=0.007). Increased of high-sensitivity cardiac troponin T and B-type natriuretic peptide levels, left ventricular diastolic diameter, left ventricular thickness, impaired left ventricular ejection fraction, and E/e’ were significantly associated with ECV CT ≥ 35%. The prevalence of cardiac amyloidosis was estimated to be at least 1.7% (15/875) in entire study patients and 14.2% (15/106) in patients with ECV CT ≥ 35%. In these cases, increased ECV CT was a clue of the diagnosis of cardiac amyloidosis. Conclusion: CCTA was useful not only for evaluation of coronary arteries but also for evaluation of myocardial properties by ECV CT . Elevated ECV CT was associated with elevated cardiac biomarkers and structural changes of myocardium. There is an incidental diagnosis of cardiac amyloidosis in approximately 1.7% of cases underwent CCTA for the purpose of coronary artery evaluation detected by increased ECV CT .

Differentiating the Prognostic Determinants of Myocardial Steatosis for Heart Failure With Preserved Ejection Fraction by Cardiac Magnetic Resonance Imaging.

Background Myocardial steatosis and fibrosis may play a role in the pathophysiology of heart failure with preserved ejection fraction. We therefore investigated the prognostic significance of epicardial fat (epicardial adipose tissue [EAT]) and myocardial diffuse fibrosis. Methods and Results Myocardial fibrosis, estimated as extracellular volume (ECV), and EAT were measured using cardiac magnetic resonance imaging in 163 subjects with heart failure with preserved ejection fraction. We also evaluated cardiac structure and diastolic and systolic function by echocardiography and cardiac magnetic resonance imaging. After 24 months' follow-up, 39 (24%) subjects had experienced cardiovascular events, including hospitalization for heart failure, acute coronary syndrome, and cardiovascular death. Median EAT and mean ECV were significantly higher in subjects with cardiovascular events thansurvivors (EAT, 35 [25-45] versus 31 [21-38], P=0.006 and ECV, 28.9±3.16% versus 27.2±3.56%, P=0.04). Subjects with high EAT (≥42 g) had increased risk of cardiovascular events (hazard ratio [HR], 2.528 [95% CI, 1.704-4.981]; P=0.032). High ECV (>29%) was also significantly associated with poorer outcomes (HR, 1.647 [95% CI, 1.263-2.548]; P=0.013). With respect to secondary end points, high EAT and high ECV were associated with increased risk of the incident acute coronary syndrome (HR, 1.982 [95% CI, 1.008-4.123]; P=0.049) and hospitalization for heart failure (HR, 1.789 [95% CI, 1.102-6.987]; P=0.033), respectively. Conclusions Our study suggested that increased epicardial fat and ECV detected by cardiac magnetic resonance imaging have an impact on cardiovascular prognosis, in particular acute coronary syndrome and hospitalization for heart failure, respectively.

Extracellular volume fraction derived from equilibrium contrast-enhanced CT as a diagnostic parameter in anterior mediastinal tumors

PurposeTo assess the usefulness of extracellular volume (ECV) fraction derived from equilibrium contrast-enhanced CT (CECT) for diagnosing anterior mediastinal tumors. MethodThis study included 161 histologically confirmed anterior mediastinal tumors (55 low-risk thymomas, 57 high-risk thymomas, 32 thymic carcinomas, and 17 malignant lymphomas) that were assessed by pretreatment CECT. ECV fraction was calculated using measurements obtained within the lesion and the aorta on unenhanced and equilibrium phase CECT. ECV fraction was compared among anterior mediastinal tumors using one-way ANOVA or t-test. Receiver-operating characteristic (ROC) curve analysis was performed to evaluate the ability of ECV fraction to differentiate thymic carcinomas/lymphomas from thymomas. ResultsECV fraction differed significantly among the anterior mediastinal tumors (p < 0.001). ECV fraction of thymic carcinomas was significantly higher than those of low-risk thymomas, high-risk thymomas, and lymphomas (p < 0.001, p < 0.001, and p = 0.006, respectively). ECV fraction of lymphomas was significantly higher than that of low-risk thymomas (p < 0.001). ECV fraction was significantly higher in thymic carcinomas/lymphomas than in thymomas (40.1 % vs. 27.7 %, p < 0.001). The optimal cutoff value to differentiate thymic carcinomas/lymphomas from thymomas was 38.5 % (AUC, 0.805; 95 %CI, 0.736–0.863). ConclusionsECV fraction derived from equilibrium CECT is helpful in diagnosing anterior mediastinal tumors. High ECV fraction is indicative of thymic carcinomas/lymphomas, particularly thymic carcinomas.

Endogenous Sex Hormone Levels and Myocardial Fibrosis in Men and Postmenopausal Women

BackgroundSex hormone (SH) imbalances have been linked to a higher risk of heart failure in both sexes. However, mechanisms that underlie this relationship remain unclear. We examined the association of baseline SH with interstitial and replacement myocardial fibrosis in the MESA (Multi-Ethnic Study of Atherosclerosis) using cardiac magnetic resonance (CMR) T1 mapping and late gadolinium enhancement (LGE). ObjectivesThe purpose of this study was to assess the link between baseline sex hormone levels and myocardial fibrosis in the MESA cohort using CMR. MethodsA total of 2,324 participants (men and postmenopausal women [PMW]) were included in the MESA with SH measured at baseline and had underwent CMR 10 years later. All analyses were stratified by sex and age. Regression models were constructed to assess the associations of baseline SH with extracellular volume (ECV)% and native T1 time and with LGE. Higher native T1 time and ECV% are interpreted as evidence of increasing interstitial myocardial fibrosis (IMF). Given the limited number of myocardial scars present in PMW, analysis of LGE was limited to men. ResultsAmong older men (age ≥65 years), a 1-SD increment higher free testosterone was significantly associated with 2.45% lower ECV% and 21.5% lower native T1 time, while a 1-SD increment higher bioavailable testosterone was associated with 12.5% lower native T1 time. A 1-SD increment greater sex hormone-binding globulin level was associated with 1% higher ECV%. Among PMW of 55 to 64 years, a 1-SD increment higher total testosterone was associated with 9.5% lower native T1 time. Higher levels of estradiol in older men were independently associated with higher odds of having a myocardial scar (OR: 4.10; 95% CI: 1.35-12.40; P = 0.01). ConclusionsAmong older men, SH imbalances at initial evaluation were independently associated with CMR defined IMF and replacement fibrosis, respectively; while increasing total testosterone in middle-aged PMW was associated with lesser marker of IMF.

Association between proteomic biomarkers and myocardial fibrosis measured by MRI: the multi-ethnic study of atherosclerosis.

Cardiac magnetic resonance imaging (CMR) determines the extent of interstitial fibrosis, measured by increased extracellular volume (ECV), and replacement fibrosis with late gadolinium myocardial enhancement (LGE). Despite advances in detection, the pathophysiology of subclinical myocardial fibrosis is incompletely understood. Targeted proteomic discovery technologies enable quantification of low abundance circulating proteins to elucidate cardiac fibrosis mechanisms. Using a cross-sectional design, we selected 92 LGE+cases and 92 LGE- demographically matched controls from the Multi-Ethnic Study of Atherosclerosis. Similarly, we selected 156 cases from the highest ECV quartile and matched with 156 cases from the lowest quartile. The plasma serum proteome was analyzed using proximity extension assays to determine differential regulation of 92 proteins previously implicated with cardiovascular disease. Results were analyzed using volcano plots of statistical significance vs. magnitude of change and Bayesian additive regression tree (BART) models to determine importance. After adjusting for false discovery, higher ECV was significantly associated with 17 proteins. Using BART, Plasminogen activator inhibitor 1, Insulin-like growth factor-binding protein 1, and N-terminal pro-B-type natriuretic peptide were associated with higher ECV after accounting for other proteins and traditional cardiovascular risk factors. In contrast, no circulating proteins were associated with replacement fibrosis. Our results suggest unique circulating proteomic signatures associated with interstitial fibrosis emphasizing its systemic influences. With future validation, protein panels may identify patients who may develop interstitial fibrosis with progression to heart failure. This research was supported by contracts and grants from NHLBI, NCATS and the Inova Heart and Vascular Institute.

Differences in Myocardial Remodeling and Tissue Characteristics in Chronic Isolated Aortic and Mitral Regurgitation.

The left ventricular hemodynamic load differs between aortic regurgitation (AR) and primary mitral regurgitation (MR). We used cardiac magnetic resonance to compare left ventricular remodeling patterns, systemic forward stroke volume, and tissue characteristics between patients with isolated AR and isolated MR. We assessed remodeling parameters across the spectrum of regurgitant volume. Left ventricular volumes and mass were compared against normal values for age and sex. We calculated forward stroke volume (planimetered left ventricular stroke volume-regurgitant volume) and derived a cardiac magnetic resonance-based systemic cardiac index. We assessed symptom status according to remodeling patterns. We also evaluated the prevalence of myocardial scarring using late gadolinium enhancement imaging, and the extent of interstitial expansion via extracellular volume fraction. We studied 664 patients (240 AR, 424 primary MR), median age of 60.7 (49.5-69.9) years. AR led to more pronounced increases in ventricular volume and mass compared with MR across the spectrum of regurgitant volume (P<0.001). In ≥moderate regurgitation, AR patients had a higher prevalence of eccentric hypertrophy (58.3% versus 17.5% in MR; P<0.001), whereas MR patients had normal geometry (56.7%) followed by myocardial thinning with low mass/volume ratio (18.4%). The patterns of eccentric hypertrophy and myocardial thinning were more common in symptomatic AR and MR patients (P<0.001). Systemic cardiac index remained unchanged across the spectrum of AR, whereas it progressively declined with increasing MR volume. Patients with MR had a higher prevalence of myocardial scarring and higher extracellular volume with increasing regurgitant volume (P value for trend <0.001), whereas they were unchanged across the spectrum of AR (P=0.24 and 0.42, respectively). Cardiac magnetic resonance identified significant heterogeneity in remodeling patterns and tissue characteristics at matched degrees of AR and MR. Further research is needed to examine if these differences impact reverse remodeling and clinical outcomes after intervention.

Comprehensive cardiac magnetic resonance T1, T2, and extracellular volume mapping to define Duchenne cardiomyopathy

BackgroundCardiomyopathy is the leading cause of death in Duchenne muscular dystrophy (DMD). Cardiac magnetic resonance (CMR) parametric mapping sequences offer insights into disease pathophysiology. We propose a novel approach by leveraging T2 mapping in conjunction with T1 and extracellular volume (ECV) mapping to perform a virtual myocardial biopsy. While previous work has attempted to describe myocardial changes in DMD, our inclusion of T2 mapping enables comprehensive categorization of myocardial tissue characteristics of fibrosis, edema, and fat to better understand the pathological composition of the myocardium with disease progression. MethodsDMD patients (n = 49; median: 12 years-old) underwent CMR, including T1, T2, and ECV. Categories were defined as normal, isolated high T1 (normal ECV, high T1, normal T2), fibrosis (high ECV, normal or high T1, normal T2), edema (normal or high ECV, normal or high T1, high T2), fat (normal ECV, low T1, high T2) or fibrofatty (high ECV, low T1, high T2). ResultsMedian left ventricular ejection fraction (LVEF) was 59% with 27% having LVEF < 55%. Those with normal LVEF and no late gadolinium enhancement (37%) were younger in age (10.5 ± 2.6 vs. 15.0 ± 4.3 years-old, p < 0.001). Native T1 was elevated in at least one slice in 82% of patients. Those with high T2 at any slice (27%) were older (p = 0.005) and had lower LVEF (p = 0.005) compared with subjects with normal T2 (73%). The most common myocardial characterization was fibrosis (43%) followed by isolated high T1 (24%). Of the 13 with high T2, ten were categorized as edema, two as fibrofatty, and one as fat. ConclusionCMR parametric mapping sequences offer insights into Duchenne cardiomyopathy pathophysiology, which should drive development of therapeutic interventions aimed at these targets. Myocardial fibrosis is common in DMD. Patients with elevated T2 were older and had lower LVEF. Though fat infiltration was present, the majority of subjects with elevated T2 met criteria for myocardial edema.

Use of Cardiac Magnetic Resonance Imaging to Distinguish Between Acute Myocarditis and Takotsubo Cardiomyopathy

Use of Cardiac Magnetic Resonance Imaging to Distinguish Between Acute Myocarditis and Takotsubo Cardiomyopathy

The cardiac computed tomography-derived extracellular volume fraction predicts patient outcomes and left ventricular mass reductions after transcatheter aortic valve implantation for aortic stenosis

BackgroundTranscatheter aortic valve implantation (TAVI) improved outcome of patients with severe aortic valve stenosis (AS). Myocardial fibrosis is associated with AS-related pathological left ventricular (LV) remodeling and predicts cardiovascular mortality after TAVI. The present study aimed to investigate the impact of preoperative extracellular volume (ECV) assessed by computed tomography (CT) on left ventricular mass (LVM) regression and clinical outcomes in severe AS patients after TAVI. MethodsWe examined 71 consecutive severe AS patients who underwent CT with ECV determination before TAVI. ECV was calculated as the ratio of the change in Hounsfield units in the myocardium and LV blood before and after contrast administration, multiplied by (1-hematocrit). Delayed scan was performed at 5 min after contrast injection. Echocardiography was performed before and 6 months after TAVI. The primary endpoint was heart failure (HF) hospitalization after TAVI. Patients were divided into two subgroups according to the median value of global ECV with 32 % (Low-ECV group: n = 35, and High-ECV group: n = 36). ResultsNo significant differences were observed in background characteristics between the 2 groups. However, the preoperative LV ejection fraction and LVM index were similar between the 2 groups, the Low-ECV group had greater LVM index reduction than the High-CV group after 6 months (p < 0.001). Kaplan-Meier curves demonstrated that the High-ECV group had significantly higher rate of HF hospitalization than the Low-ECV group (p = 0.016). In addition, multivariate analyses identified high global ECV as an independent predictor of HF hospitalization (HR 10.8, 95 % confidence interval 1.36 to 84.8, p = 0.024). ConclusionThe low preoperative ECV assessed by CT is associated with the greater LVM regression, and predict better outcome in AS patients after TAVI.