Extracellular Volume Values Research Articles

Extra cellular volume by computed tomography is useful for prediction of prognosis in cardiac sarcoidosis

Abstract Background Extracellular volume (ECV) fraction on magnetic resonance imaging (MRI) has been useful in evaluating the degree of myocardial fibrosis and has been reported to help diagnose and evaluate the prognosis of cardiomyopathy. However, there are also several contraindications in the cardiac MRI, and the performance of it takes time. Computed tomography (CT) helps screen for coronary artery disease, is more versatile than cardiac MRI, and is also useful in screening for coronary artery disease. Myocardial extracellular volume (ECV) analysis on CT has been recently eligible and has shown a good correlation with ECV on MRI. We hypothesized that ECV on CT, a new fibrosis indicator, would be useful in predicting prognosis in patients with cardiac sarcoidosis (CS). Purpose The purpose of this study is to evaluate the utility of ECV analysis on CT for predicting major adverse cardiac events (MACEs) in cases with cardiac sarcoidosis (CS). Methods As a single-center study, 48 patients (18 males, 67 ± 11 years old) diagnosed with CS based on the 2016 Japanese Circulation Society criteria and who underwent cardiac CT using 320-row detector CT or 256-row detector CT, and including late-phase images from December 2008 to January 2024 were analyzed retrospectively. We evaluated the ECV of left ventricular myocardium (LVM) using commercially available software (Figure A). The primary endpoint was MACEs, a composite of all-cause death, heart failure hospitalization, and fatal ventricular arrhythmia. Results Among all 48 patients, 14 combined events (10 fatal ventricular arrhythmias, three heart failure hospitalizations, and one all-cause death) were observed during a follow-up of 56 ± 57 months. ECV of LVM on CT was significantly higher in patients with MACEs than the others (37 ± 5.6% vs 33 ± 4.6%, P = 0.0087). The best cut-off value of ECV of LVM on CT for prediction of MACEs was 34.97%, and the sensitivity and specificity of LV-ECV to predict MACEs were 71% and 76% at the best cut-off, and the area under the curve was 0.73 based on the receiver operating characteristics curve analysis (P = 0.009) (Figure B). The cases with ECV ≥ 34.97% (n = 18) had significantly higher MACEs than the cases with ECV < 34.97% based on the Kaplan-Meier analysis (P = 0.0031) (Figure C). In the multivariate Cox proportional hazard model, ECV on LVM (Hazard ratio 1.11, 95% confidence interval 1.00-1.21, p=0.0493) and history of VT ablation (Hazard ratio 27.7, 95% confidence interval 4.27-180, p=0.0011) were the significant predictors of MACEs. Conclusion Adverse events mainly caused by fatal ventricular arrhythmia are relatively common in CS. Evaluation of ECV by CT may be useful for the prediction of MACEs in cases with CS.

Computed tomography-derived myocardial extracellular volume as a prognosis predictor in patients with severe aortic stenosis

Abstract Background Patients with severe aortic stenosis (AS) face a higher risk of mortality, but prognosis is still heterogeneous and tools for prioritizing intervention are needed. Myocardial extracellular volume (ECV), measured non-invasively in pre-TAVR computed tomography (CT), is a marker of fibrosis that may reflect the degree of irreversible damage. The aim of this study was to assess the prognostic value of CT- derived ECV (ECVCT) in patients with severe AS referred for TAVR-planning CT. Methods Consecutive patients with severe symptomatic AS undergoing TAVR-planning CT between April and December 2022 at single centre were prospectively included. CT was performed on a 192-slice dual-source 3rdgeneration scanner. ECVCT was acquired during TAVR-planning using an additional post-contrast low-radiation-dose prospective acquisition. ECVCT was calculated as the ratio of change in CT attenuation (Hounsfield units [HU]) of the septal myocardium and the left ventricle (LV) blood pool before and after contrast administration, according to the equation: ECVCT = (1 – hematocrit) x (DHUmyo/DHUblood) – Figure 1A. The primary endpoint was all-cause mortality. The secondary endpoint was a composite endpoint including all-cause mortality and heart failure hospitalization. Results A total of 138 patients were included (mean age 81 ± 7 years; 46% male; mean transaortic gradient 51 ± 15 mmHg; mean aortic valvearea 0.75 ± 0.19 cm2; mean LV ejection fraction (EF) by 2D echocardiogram 57 ± 11%). No patient had a clinical diagnosis of cardiac amyloidosis. Mean ECVCT was 33.9 ± 8.0%. During a median follow-up period of 386 days (IQR 332 – 464), there were 18 deaths (13%), 13 before intervention and 5 after intervention; the secondary endpoint occurred in 26 patients (19%), 17 of which before intervention and 9 after. Patients who attained the primary endpoint were significantly older [81 ± 7 vs. 85 ± 7 years, P = 0.011], had lower left ventricular ejection fraction [51 ± 11 vs. 58 ± 11%, P = 0.015], higher NTproBNP levels [4739 (IQR 2003 – 9970) vs. 751 (IQR 314 – 2541), P <0.001] and higher ECV values (39.9 ± 7.4% vs. 33.0 ± 7.7%, P <0.001). After adjustment for age, LVEF and NTproBNP levels, ECVCT remained an independent predictor of all-cause mortality (adjusted HR 1.09 per 1% ECV increase, 95%CI 1.02 – 1.17, p=0.005 – Figure 1B) and also the secondary endpoint (adjusted HR 1.07 per 1% ECV increase, 95%CI 1.01 – 1.13, p=0.002). Conclusions In this prospective observational cohort study, interstitial fibrosis assessed by CT-derived ECV was associated with poor outcomes in patients with severe AS. ECVCT values may be useful to identify a subgroup of patients with higher risk who may benefit from earlier intervention.

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

Extracellular Volume and Fibrosis Volume of Left Ventricular Myocardium Assessed by Cardiac Magnetic Resonance in Vaccinated and Unvaccinated Patients with a History of SARS-CoV-2 Infection.

Cardiac magnetic resonance (CMR) enables the assessment of tissue characteristics of the myocardium. Changes in the extracellular volume (ECV) and fibrosis volume (FV) of the myocardium are sensitive and early pathogenetic markers and have prognostic significance. The aim of the study was to assess ECV and FV of left ventricular myocardium in T1 mapping sequence in patients with a history of SARS-CoV-2 infection, considering vaccination status against COVID-19. The study group consisted of 97 patients (52.54 ± 8.31years, 53% women and 47% men). The participants were divided into three subgroups: A) patients with a history of symptomatic SARS-CoV-2 infection, unvaccinated against COVID-19 (n = 39), B) patients with a history of symptomatic SARS-CoV-2 infection, with a full vaccination schedule against COVID-19 (n = 22), and C) persons without a history of SARS-CoV-2 infection constituting the control subgroup (C, n = 36). All patients underwent 1.5T cardiac magnetic resonance. In subgroup A compared to subgroups B and C, both the ECV whole myocardium and ECV segments 2, 5-6, 8, and 10-11 were statistically significantly higher. In addition, the ECV segment 16 was statistically significantly higher in subgroup A than in subgroup C. Also, the FV whole myocardium was statistically significantly higher in subgroup A in comparison to subgroups B and C. There were no significant differences in ECV and FV between subgroups B and C. In summary, unvaccinated against COVID-19 patients with a history of symptomatic SARS-CoV-2 infection have higher myocardial ECV and FV values in the T1 mapping sequence, compared to those without COVID-19 and those suffering from COVID-19, previously vaccinated with the full vaccination schedule.

Free-breathing 3D cardiac extracellular volume (ECV) mapping using a linear tangent space alignment (LTSA) model.

To develop a new method for free-breathing 3D extracellular volume (ECV) mapping of the whole heart at 3 T. A free-breathing 3D cardiac ECV mapping method was developed at 3 T. T1 mapping was performed before and after contrast agent injection using a free-breathing electrocardiogram-gated inversion recovery sequence with spoiled gradient echo readout. A linear tangent space alignment model-based method was used to reconstruct high-frame-rate dynamic images from (k,t)-space data sparsely sampled along a random stack-of-stars trajectory. Joint T1 and transmit B1 estimation were performed voxel-by-voxel for pre- and post-contrast T1 mapping. To account for the time-varying T1 after contrast agent injection, a linearly time-varying T1 model was introduced for post-contrast T1 mapping. ECV maps were generated by aligning pre- and post-contrast T1 maps through affine transformation. The feasibility of the proposed method was demonstrated using in vivo studies with six healthy volunteers at 3 T. We obtained 3D ECV maps at a spatial resolution of 1.9 × 1.9 × 4.5 mm3 and a FOV of 308 × 308 × 144 mm3, with a scan time of 10.1 ± 1.4 and 10.6 ± 1.6 min before and after contrast agent injection, respectively. The ECV maps and the pre- and post-contrast T1 maps obtained by the proposed method were in good agreement with the 2D MOLLI method both qualitatively and quantitatively. The proposed method allows for free-breathing 3D ECV mapping of the whole heart within a practically feasible imaging time. The estimated ECV values from the proposed method were comparable to those from the existing method.

Enhanced detection of damaged myocardium and risk stratification in hypertrophic cardiomyopathy using integrated [68Ga]Ga-FAPI-04 PET/CMR imaging.

This study aims to explore the correlation between PET and CMR in integrated [68Ga]Ga-FAPI-04 PET/CMR multimodal imaging and its value in the diagnosis and risk assessment of hypertrophic cardiomyopathy (HCM). This study included 20 HCM patients and 11 age- and gender-matched controls. PET analysis evaluated left ventricular (LV) [68Ga]Ga-FAPI-04 uptake, including SUVmax, TBR, cardiac fibroblast activity (CFA) and volume (CFV), and total SUV of the 16 segments. CMR tissue characterization parameters included cardiac function, myocardial thickness, late gadolinium enhancement (LGE), relaxation time, extracellular volume (ECV), and peak strain parameters. The 5-year sudden cardiac death (SCD) risk score and the 2-year and 5-year atrial fibrillation (AF) risk scores were calculated for each patient. The study analyzed differences between HCM patients and controls, the correlation between [68Ga]Ga-FAPI-04 PET and concurrent CMR imaging results, and the predictive value of PET/CMR. The FAPI uptake, myocardial mass, myocardial thickness, and T1/T2 mapping values were significantly higher in HCM patients compared to controls. Twenty HCM patients and their 320 myocardial segments were discussed. Increased [68Ga]Ga-FAPI-04 uptake in the left ventricular wall was observed in 95% (19/20) of the patients, covering 48.8% (156/320) of the segments. On concurrent CMR, 80% (16/20) of the patients showed LGE, including 95 (29.7%) segments. The FAPI(+)LGE(+) segments exhibited the highest myocardial PET uptake, greatest thickness, longest T1/T2 native values, largest ECV value and the greatest loss of myocardial strain capacity (P < 0.05). There was a significant correlation between FAPI uptake and CMR parameters (P < 0.05). Higher [68Ga]Ga-FAPI-04 uptake showed a positive correlation with SCD and AF risk scores (P < 0.05). The number of LGE(+) segments, mapping parameters, and ECV values in CMR also had prognostic significance. Combining PET with CMR aided in further risk stratification of HCM. [68Ga]Ga-FAPI-04 PET/CMR multimodal imaging has potential value in the detection of damaged myocardial lesions and risk assessment of HCM patients. [68Ga]Ga-FAPI-04 PET can detect more affected myocardium compared to CMR, and segments with abnormalities in both PET and CMR show more severe myocardial damage.

Myocardial Fibrosis in Young and Veteran Athletes: Evidence from a Systematic Review of the Current Literature.

Background: Exercise is associated with several cardiac adaptations that can enhance one's cardiac output and allow one to sustain a higher level of oxygen demand for prolonged periods. However, adverse cardiac remodelling, such as myocardial fibrosis, has been identified in athletes engaging in long-term endurance exercise. Cardiac magnetic resonance (CMR) imaging is considered the noninvasive gold standard for its detection and quantification. This review seeks to highlight factors that contribute to the development of myocardial fibrosis in athletes and provide insights into the assessment and interpretation of myocardial fibrosis in athletes. Methods: A literature search was performed using the PubMed/Medline database and Google Scholar for publications that assessed myocardial fibrosis in athletes using CMR. Results: A total of 21 studies involving 1642 endurance athletes were included in the analysis, and myocardial fibrosis was found in 378 of 1595 athletes. A higher prevalence was seen in athletes with cardiac remodelling compared to control subjects (23.7 vs. 3.3%, p < 0.001). Similarly, we found that young endurance athletes had a significantly higher prevalence than veteran athletes (27.7 vs. 19.9%, p < 0.001), while male and female athletes were similar (19.7 vs. 16.4%, p = 0.207). Major myocardial fibrosis (nonischaemic and ischaemic patterns) was predominately observed in veteran athletes, particularly in males and infrequently in young athletes. The right ventricular insertion point was the most common fibrosis location, occurring in the majority of female (96%) and young athletes (84%). Myocardial native T1 values were significantly lower in athletes at 1.5 T (p < 0.001) and 3 T (p = 0.004), although they had similar extracellular volume values to those of control groups. Conclusions: The development of myocardial fibrosis in athletes appears to be a multifactorial process, with genetics, hormones, the exercise dose, and an adverse cardiovascular risk profile playing key roles. Major myocardial fibrosis is not a benign finding and warrants a comprehensive evaluation and follow-up regarding potential cardiac disease.

Additional value of CMR parametric mapping in tissue characterization of common benign pediatric cardiac tumors.

Cardiac Magnetic Resonance (CMR) parametric mapping is underexplored in cardiac tumors. To evaluate the contribution of mapping sequences on the characterization of pediatric tumors. All pediatric patients referred for cardiac tumors at Bambino Gesù Children's Hospital from June 2017 to November 2023, who underwent CMR with mapping sequences, were included. The diagnosis of tumor type was performed according to signal characteristics on different sequences. Mass parametric mapping for each subtype and interobserver variability was assessed. Sixteen patients were enrolled. The mean age at CMR was 7 ± 5 years. "Traditional" mass-type assessment diagnosed hemangioma (Group A) in 3 patients (19%), fibroma (Group B) in 4 patients (25%), rhabdomyoma (Group C) in 6 patients (37%), and lipoma (Group D) in 3 patients (19%). The ANOVA analysis revealed significant differences in mass native T1 and mass extracellular volume (ECV) values among the four subgroups (p<0.001 for both comparisons). The mean native T1 and ECV values were respectively 1465 ± 158 msec and 54 ± 4% for Group A, 860 ± 118 msec and 93 ± 4% for Group B, 1007 ± 57 msec and 23 ± 5% for Group C, and 215 ± 13 msec and 0 ± 0% for Group D. Mass mapping analysis is feasible and reproducible in children. ECV values provide the most accurate differentiation. Mass ECV consistently resembles normal myocardium in rhabdomyoma, is extremely high (approaching 100%) in fibroma, equals to zero in lipoma, and matches blood pool ECV (1-Hct) in hemangioma.

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

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

Importance of T1-Mapping Sequence in Patients with Hypertrophic Cardiomyopathy without Foci of Non-Ischemic Myocardial Injury in Late Gadolinium Enhancement Sequence.

The aim of this study was to assess the importance of T1-mapping sequences in the diagnosis of hypertrophic cardiomyopathy (HCM) in patients without foci of non-ischemic myocardial injury in classic cardiac magnetic resonance (CMR) sequences. Two groups were compared: 28 patients with HCM, without any foci of myocardial injury in the late gadolinium enhancement (LGE) sequence (HCM group), and 28 patients without cardiomyopathy (CON group). Classic CMR sequences and T1-mapping sequences were performed. The following parameters were assessed: T1 time of the whole left ventricular myocardium, T1 time of myocardium in the basal, middle and apical layers of the left ventricle, and T1 time in individual segments of the left ventricular myocardium. Myocardial extracellular volume (ECV) was assessed similarly. ECV was significantly higher in the HCM group than in the CON group, for the whole left ventricular myocardium, for the basal and apical layers of the left ventricle, and for segments 1-3, 8, and 13-16 of the left ventricle. Regression analysis showed that a higher left-ventricular mass index (LVMI), a higher body mass index and older age are factors independently associated with a higher ECV of the whole myocardium but only in the group with LVMI ≥ 131.84 g/m2. In patients with HCM without foci of non-ischemic myocardial injury, higher ECV values of the left ventricular myocardium are observed.

Extracellular volume fraction derived from dual-energy CT: a potential predictor for acute pancreatitis after pancreatoduodenectomy.

To investigate the value of extracellular volume (ECV) fraction and fat fraction (FF) derived from dual- energy CT (DECT) for predicting postpancreatectomy acute pancreatitis (PPAP) after pancreatoduodenectomy (PD). This retrospective study included patients who underwent DECT and PD between April 2022 and September 2022. PPAP was determined according to the International Study Group for Pancreatic Surgery (ISGPS) definition. Iodine concentration (IC) and FF of the pancreatic parenchyma were measured on preoperative DECT. The ECV fraction was calculated from iodine map images of the equilibrium phase. The independent predictors for PPAP were assessed by univariate and multivariable logistic regression analysisand receiver operating characteristic (ROC) curve analysis. Sixty-nine patients were retrospectively enrolled (median age, 60 years; interquartile range, 55-70 years; 47 men). Of these, nine patients (13.0%) developed PPAP. These patients had lower portal venous phase IC, equilibrium phase IC, FF, and ECV fraction, and higher pancreatic parenchymal-to-portal venous phase IC ratio and pancreatic parenchymal-to-equilibrium phase IC ratio, compared with patients without PPAP. After multivariable analysis, ECV fraction was independently associated with PPAP (odd ratio [OR], 0.87; 95% confidence interval [CI]: 0.79, 0.96; p < 0.001), with an area under the curve (AUC) of 0.839 (sensitivity 100.0%, specificity 58.3%). A lower ECV fraction is independently associated with the occurrence of PPAP after PD. ECV fraction may serve as a potential predictor for PPAP after PD. DECT-derived ECV fraction of pancreatic parenchyma is a promising biomarker for surgeons to preoperatively identify patients with higher risk for postpancreatectomy acute pancreatitis after PD and offer selective perioperative management. PPAP is a complication of pancreatic surgery, early identification of higher-risk patients allows for risk mitigation. Lower DECT-derived ECV fraction was independently associated with the occurrence of PPAP after PD. DECT aids in preoperative PAPP risk stratification, allowing for appropriate treatment to minimize complications.

Extracellular volume-based scoring system for tracking tumor progression in pancreatic cancer patients receiving intraoperative radiotherapy

ObjectivesTo investigate the value of extracellular volume (ECV) derived from portal-venous phase (PVP) in predicting prognosis in locally advanced pancreatic cancer (LAPC) patients receiving intraoperative radiotherapy (IORT) with initial stable disease (SD) and to construct a risk-scoring system based on ECV and clinical-radiological features.Materials and methodsOne hundred and three patients with LAPC who received IORT demonstrating SD were enrolled and underwent multiphasic contrast-enhanced CT (CECT) before and after IORT. ECV maps were generated from unenhanced and PVP CT images. Clinical and CT imaging features were analyzed. The independent predictors of progression-free survival (PFS) determined by multivariate Cox regression model were used to construct the risk-scoring system. Time-dependent receiver operating characteristic (ROC) curve analysis and the Kaplan–Meier method were used to evaluate the predictive performance of the scoring system.ResultsMultivariable analysis revealed that ECV, rim-enhancement, peripancreatic fat infiltration, and carbohydrate antigen 19-9 (CA19-9) response were significant predictors of PFS (all p < 0.05). Time-dependent ROC of the risk-scoring system showed a satisfactory predictive performance for disease progression with area under the curve (AUC) all above 0.70. High-risk patients (risk score ≥ 2) progress significantly faster than low-risk patients (risk score < 2) (p < 0.001).ConclusionECV derived from PVP of conventional CECT was an independent predictor for progression in LAPC patients assessed as SD after IORT. The scoring system integrating ECV, radiological features, and CA19-9 response can be used as a practical tool for stratifying prognosis in these patients, assisting clinicians in developing an appropriate treatment approach.Critical relevance statementThe scoring system integrating ECV fraction, radiological features, and CA19-9 response can track tumor progression in patients with LAPC receiving IORT, aiding clinicians in choosing individual treatment strategies and improving their prognosis.Key PointsPredicting the progression of LAPC in patients receiving IORT is important.Our ECV-based scoring system can risk stratifying patients with initial SD.Appropriate prognostication can assist clinicians in developing appropriate treatment approaches.Graphical

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.

Myocardial extracellular volume derived from contrast-enhanced chest computed tomography in longitudinal evaluation of cardiac toxicity in patients treated with immune checkpoint inhibitors.

The immune-related adverse effects after immune checkpoint inhibitors (ICIs) treatment have always been a hot topic. Although the incidence of myocarditis is not high among the related adverse effects, the mortality rate is extremely high once it occurs. In the past, the risk of cancer therapy-related cardiac dysfunction (CTRCD) after drug treatment was evaluated based on imaging examinations, but this evaluation still had certain limitations. Currently, the extracellular volume (ECV) score measurement calculated using cardiac magnetic resonance T1 mapping has become a reliable method for evaluating myocardial toxicity and computed tomography (CT) examination may become an alternative. This study aimed to longitudinally evaluate the cardiac toxicity of patients treated with ICIs using myocardial ECV derived from contrast-enhanced chest CT. A total of 500 patients with III-IV lung cancer and esophageal cancer treated with ICIs were evaluated. Participants underwent baseline examination and at least 1 follow-up examination after treatment. Contrast-enhanced chest CT-ECV, left ventricular ejection fraction (LVEF), and measurement of cardiac troponin T (cTnT) were conducted before the first treatment, 3-6 months after the first treatment, and about 12 months after the first treatment, respectively. The ECV value of the middle part of the left ventricular septum was evaluated on CT venography and plain scan, the LVEF value was evaluated by color Doppler ultrasound, and the quantity of cTnT was detected by chemiluminescence. Cancer therapy-related cardiac dysfunction was recorded. The mean baseline LVEF value was 68.51%±4.81% (N0=500), and those of LVEF1, LVEF2, and LVEF3 were 68.77%±4.30%, 68.16%±3.59%, and 66.23%±4.20%, respectively (N1=500, N2=467, and N3=361, respectively). There was no significant difference between LVEF1, LVEF2, and LVEF0 (P1=0.095, P2=0.062), whereas LVEF3 was significantly lower than LVEF0 (P<0.001). The average baseline cTnT0 value was 7.42±3.95 (N0=500). The values of cTnT1, cTnT2, and cTnT3 were 10.05±11.40, 12.24±13.59, and 14.54±14.49, respectively (N1=500, N2=467, N3=361). The values of cTnT1, cTnT2, and cTnT3 were significantly higher than cTnT0 (P1<0.001, P2<0.001, P3<0.001). The average ECV0 was 47.14%±7.48% (N0=500). ECV1, ECV2, and ECV3 were 50.85%±6.79%, 53.44%±6.96% and 52.64%±7.58% respectively (N1=500, N2=467 and N3=361). ECV1, ECV2, and ECV3 were significantly higher than ECV0 (P1<0.001, P2<0.001, P3<0.001). CTRCD occurred in 49 patients. There were significant differences between the CTRCD (+) group and the CTRCD (-) group in cTnT1, cTnT2, and cTnT3 (P1<0.001, P2<0.001, and P3<0.001, respectively) and in ECV1, ECV2, and ECV3 (P1=0.039, P2=0.041, and P3=0.013, respectively). CT-ECV began to increase at the early stage after the treatment of ICIs. CT-ECV is a potential biomarker for dynamically monitoring the cardiac toxicity of tumor patients after receiving ICIs. ECV may be used to speculate the CTRCD caused by the treatment of ICIs.

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.

Early detection of myocardial involvement by non-contrast T1ρ mapping of cardiac magnetic resonance in type 2 diabetes mellitus.

This study aims to determine the effectiveness of T1ρ in detecting myocardial fibrosis in type 2 diabetes mellitus (T2DM) patients by comparing with native T1 and extracellular volume (ECV) fraction. T2DM patients (n = 35) and healthy controls (n = 30) underwent cardiac magnetic resonance. ECV, T1ρ, native T1, and global longitudinal strain (GLS) values were assessed. Diagnostic performance was analyzed using receiver operating curves. The global ECV and T1ρ of T2DM group (ECV = 32.1 ± 3.2%, T1ρ = 51.6 ± 3.8 msec) were significantly higher than those of controls (ECV = 26.2 ± 1.6%, T1ρ = 46.8 ± 2.0 msec) (all P < 0.001), whether there was no significant difference in native T1 between T2DM and controls (P = 0.264). The GLS decreased significantly in T2DM patients compared with controls (-16.5 ± 2.4% vs. -18.3 ± 2.6%, P = 0.015). The T1ρ and native T1 were associated with ECV (Pearson's r = 0.50 and 0.25, respectively, both P < 0.001); the native T1, T1ρ, and ECV were associated with hemoglobin A1c (Pearson's r = 0.41, 0.52, and 0.61, respectively, all P < 0.05); and the ECV was associated with diabetes duration (Pearson's r = 0.41, P = 0.016). The AUC of ECV, T1ρ, GLS, and native T1 were 0.869, 0.810, 0.659, and 0.524, respectively. In T2DM patients, T1ρ may be a new non-contrast cardiac magnetic resonance technique for identifying myocardial diffuse fibrosis, and T1ρ may be more sensitive than native T1 in the detection of myocardial diffuse fibrosis.

Extracellular volume fraction as a potential predictor to differentiate lung cancer from benign lung lesions with dual-layer detector spectral CT.

Extracellular volume (ECV) fraction has been used in cardiovascular diseases, pancreatic fibrosis, and hepatic fibrosis. The diagnostic value of ECV for focal lung lesions remains to be explored. The aim of this study was to evaluate the feasibility of ECV derived from a dual-layer detector computed tomography (DLCT) to differentiate lung cancer (LC) from benign lung lesions (BLLs). Retrospectively, 128 consecutive patients with pathologically confirmed LC (n=86) or BLLs (n=42) were included. Conventional computed tomography (CT) characteristics and spectral CT parameters were assessed. All patients' hematocrits were measured to correct contrast volume distributions in blood while calculating ECV. After performing logistic regression analysis, a conventional CT-based model (Model A), DLCT-based model (Model B), combined diagnostic models (Model C), and an ECV-based model (Model D) were developed. The diagnostic effectiveness of each model was examined using the receiver operating characteristic (ROC) curve and their corresponding 95% confidence intervals (CIs). The area under the curve (AUC) of each model was compared using the DeLong test. Certain conventional CT features (such as lesion size, lobulation, spiculation, pleural indentation, and enlarged lymph nodes) differed significantly between the LC and BLL groups (all P<0.05). Statistical differences were found in the following DLCT parameters (all P<0.05): effective atomic number (Zeff) (non-enhancement), electron density (ED) (non-enhancement), ECV, iodine concentration (IC), and normalized iodine concentration (NIC). Models A, B, C, and D had AUCs of 0.801 [95% confidence interval (CI): 0.721-0.866], 0.805 (95% CI: 0.726-0.870), 0.925 (95% CI: 0.865-0.964), and 0.754 (95% CI: 0.671-0.826), respectively. The AUC of Model D (ECV) showed no significant difference from that of Models A and B (DeLong test, P>0.05). The ECV derived from DLCT may be a potential new method to differentiate LC from BLLs, broadening the scope of ECV in clinical research.

Cardiac Magnetic Resonance Imaging in COVID-19 Vaccine-Associated Myocarditis Compared With Classical Myocarditis

BackgroundStudies comparing COVID-19 vaccine-associated and classical myocarditis (CM) are lacking. ObjectivesThe purpose of this study was to compare cardiac magnetic resonance (CMR) imaging findings and short-term clinical outcomes in patients with messenger RNA COVID-19 postvaccination myocarditis (PVM) and CM. MethodsThis was a retrospective study of patients with myocarditis: 31 with PVM and 46 with CM. Patients underwent a CMR protocol scan including T1 and T2 sequences. Late gadolinium enhancement (LGE) was expressed as percentage of left ventricular myocardial mass and the extracellular volume was calculated based on precontrast and postcontrast T1 images. Clinical outcomes included heart failure hospitalizations and mortality. ResultsStudy patients were predominantly male (81% in PVM vs 89% in CM, P = 0.330). Patients with PVM had lower T1 values compared with CM (1,064.2 ± 67.0 ms vs 1,081.6 ± 41.9 ms, P = 0.032), although T2 and extracellular volume values were similar in both groups. Left ventricular ejection fraction and LGE were similar in both groups. The most frequent location of LGE was the basal inferolateral wall. PVM more commonly demonstrated a mid-wall LGE pattern while CM demonstrated a subepicardial LGE pattern. Compared with CM, patients with PVM were more likely to have a pericardial effusion (42% vs 17%, P = 0.018) and pericardial LGE (38% vs 13%, P = 0.009). During short-term follow-up (median 300 days for PVM, 319 days for CM), there were no deaths or heart failure hospitalizations in either group. ConclusionsOur study shows similar CMR imaging findings and short-term outcomes in PVM and CM, although PVM was associated with milder myocardial abnormalities and more frequent pericardial involvement.

Is myocardial fibrosis appropriately assessed by 2D strain derived integrated backscatter?

Abstract Introduction Calibrated integrated backscatter (cIB) may be obtained from bidimensional (2D) strain echocardiography as a quantification measurement of myocardial ultrasound reflectivity. Increased collagen content of the myocardium modifies tissue reflectivity and cIB is suggested as a marker of left ventricular (LV) fibrosis. However, its diagnostic accuracy is not fully established. Aim To assess the correlation between cIB by 2D strain and LV myocardial fibrosis (MF), as evaluated by non-invasive imaging and histopathology. Methods Correlation study from a cohort of 157 patients with severe symptomatic aortic stenosis (AS) referred for surgical aortic valve replacement (AVR). Patients with complete preoperative transthoracic echocardiography, cardiac magnetic resonance (CMR) and endomyocardial biopsy (EMB) obtained from the anterior basal septum at the time of AVR were selected. Two groups of 30 patients were evaluated, with and without late gadolinium enhancement (LGE) at CMR. Integrated Backscatter was obtained at QRS peak in decibels (dB) from both parasternal long axis (PLAX) and apical-three-chamber (A3C) cine clips at Qanalysis. cIB was calculated by subtracting the pericardial intensity from the average of the anteroseptal and basal inferolateral wall values. Correlation analysis was performed for the whole group of patients with global and segmental (anterior basal septum) values of native T1 and extracellular volume (ECV), and EMB collagen volume fraction (CVF) from Masson´s Trichrome staining. IBS values were compared in both group of patients. Results 60 patients (74 [36-74] years, 45% male) with high gradient (mean gradient: 63±20mmHg), normal flow (45±10mL/m2), preserved ejection fraction (60±9%) AS were included. Basal septal cIB was –9.17±9.45dB and –17.45 (–31.2–10.95) dB from A3C and PLAX views, respectively. These indexes did not correlate with basal septum thickness or global LV mass. Absolute and cIB did not correlate neither with global and regional T1 and ECV values, nor with CVF at EMB. These were not significantly different in both groups of patients and there was no correlation between cIB values and mass of replacement MF in patients with LGE. Conclusion In these cohort of patients with classical severe AS, there was no correlation of cIB with imaging markers of both replacement and diffuse MF. cIB also didn´t correlate with CVF at histopathology. These findings suggest that reflectivity indexes are not suitable for myocardial tissue characterization in this setting.

Left ventricular fibrosis and CMR tissue characterization of papillary muscles in mitral valve prolapse patients.

Mitral valve prolapse (MVP) is associated with left ventricle (LV) fibrosis, including the papillary muscles (PM), which is in turn linked to malignant arrhythmias. This study aims to evaluate comprehensive tissue characterization of the PM by cardiovascular magnetic resonance (CMR) imaging and its association with LV fibrosis observed by intraoperative biopsies. MVP patients with indication for surgery due to severe mitral regurgitation (n = 19) underwent a preoperative CMR with characterization of the PM: dark-appearance on cine, T1 mapping, conventional bright blood (BB) and dark blood (DB) late gadolinium enhancement (LGE). CMR T1 mapping was performed on 21 healthy volunteers as controls. LV inferobasal myocardial biopsies were obtained in MVP patients and compared to CMR findings. MVP patients (54 ± 10 years old, 14 male) had a dark-appearance of the PM with higher native T1 and extracellular volume (ECV) values compared with healthy volunteers (1096 ± 78ms vs. 994 ± 54ms and 33.9 ± 5.6% vs. 25.9 ± 3.1%, respectively, p < 0.001). Seventeen MVP patients (89.5%) had fibrosis by biopsy. BB-LGE + in LV and PM was identified in 5 (26.3%) patients, while DB-LGE + was observed in LV in 9 (47.4%) and in PM in 15 (78.9%) patients. DB-LGE + in PM was the only technique that showed no difference with detection of LV fibrosis by biopsy. Posteromedial PM was more frequently affected than the anterolateral (73.7% vs. 36.8%, p = 0.039) and correlated with biopsy-proven LV fibrosis (Rho 0.529, p = 0.029). CMR imaging in MVP patients referred for surgery shows a dark-appearance of the PM with higher T1 and ECV values compared with healthy volunteers. The presence of a positive DB-LGE at the posteromedial PM by CMR may serve as a better predictor of biopsy-proven LV inferobasal fibrosis than conventional CMR techniques.