Segmental Late Gadolinium Enhancement Research Articles

LMNA–RELATED DILATED CARDIOMYOPATHY PRESENTING WITH REGIONAL WALL AKINESIS AND TRANSMURAL LATE GADOLINIUM ENHANCEMENT

Abstract A 26–year–old girl was admitted at hospital in December 2022 for a syncopal episode. She referred fatigue and dyspnea in the last 2 months. EKG was markedly abnormal showing peripheral low voltages, poor R wave progression in prechordial leads, negative T waves V4–V6, DII, DIII and aVF, fragmented QRS (Fig.1). Echo showed moderately dilated left ventricle (LV) with apical akinesia and apical aneurysm (no thrombi) and hypo–akinesia and hyperechoic appearance of the middle segments of the infero–posterior and lateral wall (Fig.2a). EF was 38%. There was no family history for sudden cardiac death and cardiomyopathy. Creatine kinase and neurological examination were normal. The diagnostic work–up included: myocardial scintigraphy which showed fixed tracer uptake deficit at apical and posterolateral levels (Fig.2b); cardiac magnetic resonance (CMR): apical aneurysm with extended late gadolinium enhancement (LGE) due to fibrosis, focally transmural, on the left ventricle’s midapical and infero–lateral thinned–hypokinetic myocardial walls (Fig.3a, 3b); Coronary angiography showed no stenosis. Due to myocardial aneurysm in absence of CAD, Chagas disease was excluded. We performed LV endomyocardial biopsy which showed cardiomyopathic changes and replacement fibrosis. Due to fibrosis extension, complex ventricular extrasystoles detected on monitoring and syncope, ICD was implanted. Finally genetic testing showed c.1621C>Tp.Arg541Cys LMNA pathogenetic mutation leading to the diagnosis of LMNA–related LV cardiomyopathy, with extensive fibrosis in multiple areas of left ventricle including the apical segments at a very young age. Patients with LMNA mutation-related heart disease are characterized by conduction abnormalities, ventricular tachyarrhythmias (VA) and high risk of sudden cardiac death with mildly impaired systolic function, often without chamber dilation. About 88% LMNA– cardiomyopathy have typical myocardial fibrosis, predominantly in the mid-myocardium of the basal septum. However, our patient and previous reported cases with the same p.R541 LMNA mutation presents with a specific phenotype including regional LV akinesis, segmental transmural LGE, significant LV dilatation and systolic dysfunction and VA without conduction abnormality. Of note, EKG shows normal A–V conduction but low voltage and negative T waves in precordial and inferior leads. These features are not typical for LMNA–disease and underline the phenotypic variability of cardiomyopathies.

Prognostic impact of the extent, location, and pattern of late gadolinium enhancement in dilated cardiomyopathy

Abstract Background Several studies have shown that the presence and extent of late gadolinium enhancement (LGE) defined by cardiac magnetic resonance imaging (CMR) are strong prognosticators of death in patients with dilated cardiomyopathy (DCM). The interest of LGE location and pattern to improve risk stratification is not well established. Purpose To assess the incremental prognostic value of LGE extent, location and pattern for predicting all-cause death over traditional risk factors in DCM patients. Methods Between 2008 and 2021, we conducted a bi-centre longitudinal study including all consecutive DCM patients referred for CMR. DCM was confirmed excluding patients with ischemic heart disease, history of acute myocarditis, hypertrophic cardiomyopathy, and infiltrative disease. The outcome was all-cause death using the electronic French National Registry of Death. The prognostic value of LGE parameters was assessed using Cox analyses after adjustment for traditional prognostic factors: LGE presence, extent (number of segments), pattern (midwall or subepicardial), location and multiple areas. The incremental prognostic value of these LGE parameters was assessed using C-statistic increment, the continuous net reclassification improvement (NRI), the integrative discrimination index (IDI) and the global Chi-2. Results In 2,752 DCM patients (52±8 years, 56% male), 408 (15%) died after a median (IQR) follow-up of 9.2 (6.8-11.5) years. A total of 737 (27%) patients had LGE, including 664 (90%) LGE mid-wall and 73 (10%) LGE sub-epicardial. In the whole cohort (n=2,752), the LGE presence and extent were strong predictors of death (HR: 2.42 [95% CI: 1.67-3.51] and HR: 1.78 [95% CI: 1.64-1.93]; both p<0.001). In the subgroup of patients with LGE (n=737), the LGE multiple area was an independent predictor of death (HR: 5.12 with 95% CI: 3.53-7.41; p<0.001). The LGE pattern wasn't associated with death (subepicardial: HR: 0.88; 95% CI: 0.56-1.39, p=0.58). The location in both septal and free-wall was strongly associated with death compared to septal LGE only (HR: 10.1; 95% CI: 7.53-13.6; p<0.001), itself more at risk of death than free-wall LGE only (HR: 3.12; 95% CI: 2.03-4.78; p<0.001). In the 537 patients with LGE single area, LGE in septal segments was a strong prognostic marker (HR: 17.0; 95% CI: 5.88-49.4; p<0.001) compared to other locations (inferior: HR: 10.3; 95% CI: 3.45-30.5; p<0.001; lateral: HR: 6.13; 95% CI: 1.95-19.2; p<0.01; reference=anterior). A model combining the LGE extent, location and multiple area showed the best improvement in model discrimination and reclassification above traditional risk factors (C-statistic improvement: 0.19; NRI=11.8%; IDI=2.2%, all p<0.001). Conclusion In a large cohort of DCM patients, the LGE extent, location, and multiple area were independent prognosticators of death. A model combining these LGE findings had an incremental prognostic value over traditional prognostic factors to predict all-cause death.Incremental prognostic value of LGEHazard ratios regarding LGE segments

Genetics, patterns of hypertrophy and fibrosis on myocardial mechanics in hypertrophic cardiomyopathy

Abstract Funding Acknowledgements Type of funding sources: None. Background Asymmetrical hypertrophy, myocyte disarray and fibrosis due to genetic cause are underlying pathology of hypertrophic cardiomyopathy (HCM). However, their contribution to myocardial functional mechanics are not extensively evaluated yet. Purpose In this study, we sought to investigate effects of genetic mutation, patterns of ventricular hypertrophy and fibrosis on myocardial mechanics in HCM. Methods In 133 patients with HCM, chamber geometry, segmental late gadolinium enhancement (LGE), extracellular volume fraction (ECV) by cardiac magnetic resonance imaging (CMR), echo-derived diastolic function analyses and genetic test were performed. Left ventricular (LV) segmental and global longitudinal strain (LS), circumferential strain (CS), and rotation were measured by feature tracking analysis of CMR. Results Patients with sarcomere gene mutation (SM) had lower LV-CS (global and all three slices) along with higher prevalence of midwall type LGE, LGE amount and ECV. Despite global LS was not lower in SM, anteroseptal-LS was significantly impaired accompanying with higher septal wall thickness. To compensate impaired anteroseptal LS, basal endocardial rotation was paradoxically increased in SM. Augmented basal segmental was significantly related to obstructive HCM. In apical HCM, although apical segmental LS was significantly lower, higher apical rotation and preserved apical CS along with lower prevalence of SM. The E/e’ was significantly related to LV mass index, LGE extent but not with SM. Conclusion Circumferential myocardial function was significantly reduced in SM independent of fibrosis extent, suggesting primary phenotype. However, longitudinal fiber function was more related to hypertrophy regardless of SM. LV diastolic function was more related to LV mass, extent and degree of fibrosis including non-thickened myocardium regardless of SM.

Predicting Left Ventricular Myocardial Fibrosis in Patients with Hypertrophic Cardiomyopathy by Speckle Tracking Automated Functional Imaging.

The study was performed to explore the predictive value of multiple strain parameters for myocardial fibrosis in patients with hypertrophic cardiomyopathy (HCM) by using speckle tracking automated functional imaging (AFI). A total of 61 patients diagnosed with HCM were finally enrolled in this study. All patients completed transthoracic echocardiography and cardiac magnetic resonance late gadolinium enhancement (LGE) within 1 month. Twenty age- and sex-matched healthy participants were included as the control group. Multiple parameters, including segmental longitudinal strain (LS), global longitudinal strain (GLS), post-systolic index and peak strain dispersion, were automatically analyzed by AFI. A total of 1458 myocardial segments were analyzed according to the left ventricular 18-segment model. Among the 1098 segments from HCM patients, segments with LGE had a lower absolute value of segmental LS than those without LGE (p < 0.05). The cutoff values of segmental LS for predicting positive LGE in the basal, intermediate and apical regions were -12.5%, -11.5% and -14.5%, respectively. GLS could predict significant myocardial fibrosis (≥2 positive LGE segments) at a cutoff value of -16.5% with a sensitivity of 80.9% and specificity of 76.5%. As an independent predictor of significant myocardial fibrosis, GLS was substantially associated with the severity of myocardial fibrosis and 5 years sudden cardiac death risk score in HCM patients. Speckle tracking AFI could efficiently identify left ventricular myocardial fibrosis in patients with HCM by multiple parameters. GLS predicted significant myocardial fibrosis at a cutoff value of -16.5%, which may indicate the adverse clinical outcomes in HCM patients.

Left Ventricular Fibrosis Assessment by Native T1, ECV, and LGE in Pulmonary Hypertension Patients.

Cardiac magnetic resonance imaging (MRI) is emerging as an alternative to right heart catheterization for the evaluation of pulmonary hypertension (PH) patients. The aim of this study was to compare cardiac MRI-derived left ventricle fibrosis indices between pre-capillary PH (PrePH) and isolated post-capillary PH (IpcPH) patients and assess their associations with measures of ventricle function. Global and segmental late gadolinium enhancement (LGE), longitudinal relaxation time (native T1) maps, and extracellular volume fraction (ECV) were compared among healthy controls (N = 25; 37% female; 52 ± 13 years), PH patients (N = 48; 60% female; 60 ± 14 years), and PH subgroups (PrePH: N = 29; 65% female; 55 ± 12 years, IpcPH: N = 19; 53% female; 66 ± 13 years). Cardiac cine measured ejection fraction, end diastolic, and end systolic volumes and were assessed for correlations with fibrosis. LGE mural location was qualitatively assessed on a segmental basis for all subjects. PrePH patients had elevated (apical-, mid-antero-, and mid-infero) septal left ventricle native T1 values (1080 ± 74 ms, 1077 ± 39 ms, and 1082 ± 47 ms) compared to IpcPH patients (1028 ± 53 ms, 1046 ± 36 ms, 1051 ± 44 ms) (p < 0.05). PrePH had a higher amount of insertional point LGE (69%) and LGE patterns characteristic of non-vascular fibrosis (77%) compared to IpcPH (37% and 46%, respectively) (p < 0.05; p < 0.05). Assessment of global LGE, native T1, and ECV burdens did not show a statistically significant difference between PrePH (1.9 ± 2.7%, 1056.2 ± 36.3 ms, 31.2 ± 3.7%) and IpcPH (2.7 ± 2.7%, 1042.4 ± 28.1 ms, 30.7 ± 4.7%) (p = 0.102; p = 0.229 p = 0.756). Global native T1 and ECV were higher in patients (1050.9 ± 33.8 and 31.0 ± 4.1%) than controls (28.2 ± 3.7% and 1012.9 ± 29.4 ms) (p < 0.05). Cardiac MRI-based tissue characterization may augment understanding of cardiac involvement and become a tool to facilitate PH patient classification.

1099 ERGOREFLEX SENSITIVITY IS ASSOCIATED WITH CARDIAC INVOLVEMENT IN BECKER MUSCULAR DYSTROPHY

Abstract Background and aims Becker muscular dystrophy (BMD) is a X-linked recessive inherited skeletal myopathy due to dystrophin deficiency ensuing in a variable phenotype characterized by slowly progressing muscle weakness and, often, the development of dilated cardiomyopathy. The relationship between muscle and cardiac involvement in BMD is yet to be clarified. We aimed to assess the association between ergoreflex sensitivity, a marker of skeletal muscle work regulating ventilatory and autonomic responses to exercise, and cardio-muscular involvement in BMD. Methods Fifteen male BMD patients (median age 37 years [25-42]) underwent a comprehensive evaluation including ECG, biohumoral assessment (high sensitivity troponin T/I [hs-TnT/I], natriuretic peptides, soluble suppression of tumorigenesis 2 [sST2], catecholamines, creatine phosphokinase [CPK], myoglobin), cardiac magnetic resonance (CMR), and ergoreflex determination. Muscular phenotype was distinguished into “classic” (proximal weakness affecting the shoulders and pelvis with waddling gait) or “mild”. Cardiac involvement was defined based on the presence of late gadolinium enhancement (LGE) at CMR. Ergoreflex sensitivity was calculated as the percentage of the ventilatory response to a handgrip exercise maintained by circulatory occlusion through the inflation of a forearm tourniquet (clamp) during the third minute of recovery compared with the third minute of recovery without clamp: [(Rec∕Ex) clamp − (Rec∕Ex) no clamp]∗100, where Ex is the mean ventilation during the last 30 s of exercise, Rec the mean ventilation during the last 30 s of the third minute of recovery. Results Ten patients (67%) had a “classic” muscular phenotype. Nine patients (60%) had LGE at CMR (median number of segments 9 [6-12]). The percentage of patients with cardiac involvement was not different between those with “classic” or mild muscular phenotype. Patients with cardiac involvement had higher ergoreflex sensitivity (24% [8-38] vs. 4% [0-24], p=0.036), hs-TnI (9.8 ng/L [5.9-14.5] vs. 2.1 ng/L [1.7-4.5], p=0.018), and hs-TnT (24 ng/L [20-35] vs. 11 ng/L [5-20], p=0.012), but did not show significant differences in terms of cardiac chamber size or systolic function compared to those without LGE. Ergoreflex sensitivity correlated with biomarkers of both cardiac (hs-TnI, rho=0.654, p=0.008; hs-TnT, rho=0.529, p=0.043; sST2, rho=0.654, p=0.009) and muscular damage (CPK, rho=0.645, p=0.009), as well as with the number of LGE segments (rho=0.583, p=0.022). No difference in ergoreflex sensitivity was detected in patients with “classic” versus mild muscular phenotype. Conclusions In BMD, there is no relationship between cardiac involvement and the muscular phenotype. Nonetheless, cardiac involvement in BMD is characterized by enhanced ergoreflex sensitivity, which is associated with biomarkers of both cardiac and muscular damage.

Abstract 14447: Multi-Center Evaluation of Stress Myocardial Blood Flow by Cardiac Magnetic Resonance in Known and Suspected Ischemic Heart Disease: Preliminary Findings From the AQUA-MBF Initiative

Introduction: Quantitative myocardial blood flow (MBF) analysis using stress cardiac magnetic resonance (CMR) has been shown to detect obstructive coronary artery disease (CAD) and coronary microvascular dysfunction (CMD) in several mostly small, single-center studies. The AQUA-MBF ( A ssessment of QUA ntitative MBF ) study is a multicenter initiative involving 16 centers. Hypothesis: The goal of this sub-study is to determine if MBF can differentiate CAD, CMD, and normal volunteers in this multicenter setting. Methods: We present data from 53 subjects (15 with CAD, 20 at risk for CMD and 18 controls) who underwent vasodilator stress CMR (Figure) using 1.5T and 3.0T MR scanners (General Electric). At risk for CMD was defined as having diabetes and 2 other risk factors in absence of ≥50% stenosis based on coronary CT. CAD was defined as the presence of stenosis ≥70% based on invasive coronary angiography. Stress perfusion images were acquired using the dual sequence technique. Stress MBF was measured in each of the 16 AHA segments using Fermi deconvolution (Circle Cvi42). In the CAD group, each segment was further classified as having late gadolinium enhancement (LGE), supplied by CAD, or a normal remote territory. The means of the 5 groups were compared using one-way analysis of variance. Results: The segmental stress MBF (ml/g/min) for the 5 groups are shown in figure. Compared to the normal group, segmental stress MBF in 4 disease groups were significantly lower (p&lt;0.001). Segmental MBF in those at risk for CMD was lower than normal segments and greater than CAD segments (p&lt;0.001). LGE and CAD segments had the lowest stress MBF but similar to each other (p=0.9). Conclusions: In this multicenter study, we show that quantification of MBF using the dual sequence stress perfusion CMR technique can differentiate diseased from healthy myocardium and also between obstructive CAD and those at risk for CMD.

Impact of late gadolinium enhancement extent, location, and pattern on ventricular tachycardia and major adverse cardiac events in patients with ischemic vs. non-ischemic cardiomyopathy.

Left ventricular late gadolinium enhancement (LGE) by cardiac magnetic resonance (CMR) has been associated with increased risk for life-threatening ventricular tachyarrhythmias. The differences in association between LGE characteristics and prognosis in patients with ischemic (ICM) vs. non-ischemic (NICM) cardiomyopathy is incompletely understood. A total of 168 consecutive patients who underwent CMR imaging with either ICM or NICM were included in our study. LGE extent, location and pattern were examined for association to the primary endpoint of ventricular tachycardia (VT) and secondary endpoint of major adverse cardiac events (MACE). Of 68 (41%) patients with ICM and 97 (59%) patients with NICM, median LGE mass was 15% (IQR 9-28) for the ICM group and 10% (IQR 6-15) for the NICM group. On multivariate analysis for both groups, LGE characteristics were prognostic while LVEF was not. In patients with ICM, septal and apical segment LGE, and involvement of multiple walls predicted both endpoints on multivariate analysis. LGE extent (≥median) and inferior wall LGE independently predicted the primary endpoint. In patients with NICM, anterior, inferior and apical segment LGE, and involvement of multiple walls predicted both endpoints on multivariate analysis. LGE extent (≥median, number of LGE segments, LGE stratified per 5% increase) and midwall LGE were independent predictors of the primary endpoint. Although LGE was an independent predictor of prognosis in both groups, LGE extent, location, and pattern characteristics were more powerful correlates to worse outcomes in patients with NICM than ICM.

Late gadolinium enhancement patterns in severe symptomatic high-gradient aortic stenosis

Abstract Background Left ventricular (LV) remodeling in patients with severe aortic valve stenosis (AS) is a complex process that goes beyond hypertrophic response and may involve reparative/replacement fibrosis. Currently, cardiac magnetic resonance (CMR) is the gold-standard imaging technique for detecting focal myocardial fibrosis through late gadolinium enhancement (LGE). However, myocardial fibrosis prevalence and distribution is quite variable among series. Our goal was to assess LGE prevalence and distribution pattern in severe symptomatic high-gradient AS. Methodology Single-center prospective cohort of 132 patients with severe symptomatic high-gradient AS (mean age 73±11 years; 48% male, mean valvular transaortic gradient 60±20 mmHg; mean aortic valve area 0.7±0.2 cm2/m2; mean LV ejection fraction by 2D echocardiogram 58±9%), all with normal flow (except one) undergoing surgical aortic valve replacement. Those with previous history of acute myocardial infarction, ischemic cardiomyopathy or other cardiomyopathy were excluded. All patients performed 1.5T CMR assessment with LV myocardium tissue characterization prior to surgery. Segmental LGE presence was assessed by two independent operators and classified according to the AHA 16 segment model, using 5-standard deviations from remote myocardium as the signal intensity cut-off for LGE identification and quantification. Results Overall, 96 patients (74%) had non-ischemic LGE (median LGE mass 3.2 g [IQR 0.2–8.3] g; median percentage of LGE myocardial mass 2.5% [IQR 0.1–6.1]%); 22 patients [17%] with exclusively junctional LGE); in one patient an incidental ischemic scar (subendocardial distribution) was identified. No cases of subepicardial distribution were found. Intramyocardial LGE was most frequently observed in basal and mid-anterior and inferior interventricular septum – see Figure 1. In these segments, LGE was most often junctional at right-ventricular insertion points (54%), followed by mid-wall LGE (32%) or both sites involvement (14%). Conclusion LGE is frequent in symptomatic high-gradient AS patients with preserved left ventricular ejection fraction, most often presenting as junctional enhancement in basal/mid-anterior and inferior interventricular septum. Future studies may address whether distinct LGE patterns may impact patient prognosis. Funding Acknowledgement Type of funding sources: None.

Myocardial scar detection in free-breathing Dixon-based fat- and water-separated 3D inversion recovery late-gadolinium enhancement whole heart MRI

The aim of this study was to investigate the diagnostic accuracy and reader confidence for late-gadolinium enhancement (LGE) detection of a novel free-breathing, image-based navigated 3D whole-heart LGE sequence with fat–water separation, compared to a free-breathing motion-corrected 2D LGE sequence in patients with ischemic and non-ischemic cardiomyopathy. Cardiac MRI patients including the respective sequences were retrospectively included. Two independent, blinded readers rated image quality, depiction of segmental LGE and documented acquisition time, SNR, CNR and amount of LGE. Results were compared using the Friedman or the Kruskal–Wallis test. For LGE rating, a jackknife free-response receiver operating characteristic analysis was performed with a figure of merit (FOM) calculation. Forty-two patients were included, thirty-two were examined with a 1.5 T-scanner and ten patients with a 3 T-scanner. The mean acquisition time of the 2D sequence was significantly shorter compared to the 3D sequence (07:12 min vs. 09:24 min; p < 0.001). The 3D scan time was significantly shorter when performed at 3 T compared to 1.5 T (07:47 min vs. 09:50 min; p < 0.001). There were no differences regarding SNR, CNR or amount of LGE. 3D imaging had a significantly higher FOM (0.89 vs. 0.78; p < 0.001). Overall image quality ratings were similar, but 3D sequence ratings were higher for fine anatomical structures. Free-breathing motion-corrected 3D LGE with high isotropic resolution results in enhanced LGE-detection with higher confidence and better delineation of fine structures. The acquisition time for 3D imaging was longer, but may be reduced by performing on a 3 T-scanner.

Diagnostic performance of cardiac magnetic resonance segmental myocardial strain for detecting microvascular obstruction and late gadolinium enhancement in patients presenting after a ST-elevation myocardial infarction.

BackgroundMicrovascular obstruction (MVO) and Late Gadolinium Enhancement (LGE) assessed in cardiac magnetic resonance (CMR) are associated with adverse outcome in patients with ST-elevation myocardial infarction (STEMI). Our aim was to analyze the diagnostic performance of segmental strain for the detection of MVO and LGE.MethodsPatients with anterior STEMI, who underwent additional CMR were enrolled in this sub-study of the CARE-AMI trial. Using CMR feature tracking (FT) segmental circumferential peak strain (SCS) was measured and the diagnostic performance of SCS to discriminate MVO and LGE was assessed in a derivation and validation cohort.ResultsForty-eight STEMI patients (62 ± 12 years old), 39 (81%) males, who underwent CMR (i.e., mean 3.0 ± 1.5 days) after primary percutaneous coronary intervention (PCI) were included. All patients presented with LGE and in 40 (83%) patients, MVO was additionally present. Segments in all patients were visually classified and 146 (19%) segments showed MVO (i.e., LGE+/MVO+), 308 (40%) segments showed LGE and no MVO (i.e., LGE+/MVO–), and 314 (41%) segments showed no LGE (i.e., LGE–). Diagnostic performance of SCS for detecting MVO segments (i.e., LGE+/MVO+ vs. LGE+/MVO–, and LGE–) showed an AUC = 0.764 and SCS cut-off value was –11.2%, resulting in a sensitivity of 78% and a specificity of 67% with a positive predictive value (PPV) of 30% and a negative predictive value (NPV) of 94% when tested in the validation group. For LGE segments (i.e., LGE+/MVO+ and LGE+/MVO– vs. LGE–) AUC = 0.848 and SCS with a cut-off value of –13.8% yielded to a sensitivity of 76%, specificity of 74%, PPV of 81%, and NPV of 70%.ConclusionSegmental strain in STEMI patients was associated with good diagnostic performance for detection of MVO+ segments and very good diagnostic performance of LGE+ segments. Segmental strain may be useful as a potential contrast-free surrogate marker to improve early risk stratification in patients after primary PCI.

The Combination of Feature Tracking and Late Gadolinium Enhancement for Identification Between Hypertrophic Cardiomyopathy and Hypertensive Heart Disease.

BackgroundThe differentiation between hypertrophic cardiomyopathy (HCM) and hypertensive heart disease (HHD) is challenging due to similar myocardial hypertrophic phenotype. The purpose of this study is to evaluate the feasibility of cardiovascular magnetic resonance feature tracking (CMR-FT) and late gadolinium enhancement (LGE) to distinguish between HCM and HHD and the potential relationship between myocardial strain and cardiac functional parameters.MethodsOne hundred and seventy subjects (57 HCM, 45 HHD, and 68 controls) underwent 3.0 T CMR, including steady-state free precession cines and LGE images. Global and segmental (basal, mid, and apical) analyses of myocardial radial, circumferential, longitudinal strain, and left ventricular (LV) torsion, as well as global and 16 segments of LGE were assessed. The multivariate analysis was used to predict the diagnostic ability by combining comprehensive myocardial strain parameters and LGE.ResultsGlobal radial strain (GRS), global circumferential strain (GCS), and LV torsion were significantly higher in the HCM group than in the HHD group (GRS, 21.18 ± 7.52 vs. 14.56 ± 7.46%; GCS, −13.34 ± 3.52 vs. −10.11 ± 4.13%; torsion, 1.79 ± 0.69 vs. 1.23 ± 0.65 deg/cm, all P < 0.001). A similar trend was also seen in the corresponding strain rate. As for segmental strain analysis, basal radial strain (BRS), basal circumferential strain (BCS), basal longitudinal strain (BLS), mid-radial strain (MRS), and mid-circumferential strain (MCS) were higher in the HCM group than in the HHD group (all P < 0.001). The receiver operating characteristic (ROC) results showed that the area under the curve (AUC) of LGE in the mid-interventricular septum (mIVS) was the highest among global and segmental LGE analyses. On the multivariate regression analysis, a combined model of LGE (mIVS) with GRS obtained the highest AUC value, which was 0.835 with 88.89% sensitivity and 70.18% specificity, respectively. In addition, for patients with HCM, GRS, GCS, and global longitudinal strain had correlations with LV ejection fraction (LVEF), maximum interventricular septum thickness (IVST max), and left ventricular mass index (LVMi). Torsion was mildly associated with LVEF.ConclusionCMR-FT-derived myocardial strain and torsion provided valuable methods for evaluation of HCM and HHD. In addition, the combination of GRS and LGE (mIVS) achieved the highest diagnostic value.

Predictive Value of Echocardiographic Strain for Myocardial Fibrosis and Adverse Outcomes in Autoimmune Diseases

BackgroundMyocardial fibrosis is an important pathophysiologic mechanism of cardiac involvement that leads to increased mortality in patients with autoimmune diseases (AIDs). The aim of this study was to evaluate the association between myocardial strain from speckle-tracking echocardiography (STE) and fibrosis on cardiovascular magnetic resonance (CMR) and to further explore their prognostic implications in patients with AIDs.MethodsWe prospectively included 102 AIDs patients with clinically suspected cardiac involvement and 102 age- and sex-matched healthy individuals. Patients underwent CMR for evaluation of myocardial fibrosis by late gadolinium enhancement (LGE) and T1 mapping. A semiquantitative evaluation based on the extent of LGE was used to calculate the total (tLGEs) and segmental (sLGEs) LGE score. Global longitudinal strain (GLS) was evaluated by STE in all subjects. All patients were regularly followed up every 6 months. The primary endpoint was the composite incidence of all-cause death and cardiovascular hospitalization.ResultsCompared to healthy controls, AIDs patients had impaired GLS (−17.9 ± 5.1% vs. −21.2 ± 2.5%, p < 0.001). LGE was detected in 70% of patients. Patients with LGE presented worse GLS (−17.1 ± 5.3% vs. −19.6 ± 4.1%, p = 0.018) than those without LGE. On multivariate logistic analysis, GLS ≥ −15% was an independent predictor of LGE presence (OR = 4.98, 95%CI 1.35–18.33, p = 0.016). Moreover, a marked and stepwise impairment of segmental longitudinal strain (−19.3 ± 6.6 vs. −14.9 ± 6.5 vs. −8.9 ± 6.3, p < 0.001) was observed as sLGEs increased. During a median follow-up time of 25 months, 6 patients died, and 14 patients were hospitalized for cardiovascular reasons. Both GLS ≥ −15% (HR 3.56, 95%CI 1.28–9.86, p = 0.015) and tLGEs ≥ 6 (HR 4.13, 95%CI 1.43–11.92, p = 0.009) were independently associated with the primary endpoint.ConclusionsIn AIDs patients, impaired myocardial strain on STE could reflect the presence and extent of myocardial fibrosis and provide incremental prognostic value in addition to LGE in the prediction of adverse outcomes.

Hybrid CMR- and FDG-PET-Imaging Gives New Insights Into the Relationship of Myocardial Metabolic Activity and Fibrosis in Patients With Becker Muscular Dystrophy.

BackgroundCardiac involvement in patients with Becker muscular dystrophy (BMD) is an important predictor of mortality. The cardiac phenotype of BMD patients is characterized by slowly progressive myocardial fibrosis that starts in the left ventricular (LV) free wall segments and extends into the septal wall during the disease course.PurposeSince the reason for this characteristic cardiac phenotype is unknown and comprehensive approaches using e.g. hybrid imaging combining cardiovascular magnetic resonance (CMR) with 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET) are limited, the present study addressed this issue by a comprehensive non-invasive imaging approach.MethodsHybrid CMR- and FDG-PET-imaging was performed in N = 14 patients with BMD on a whole-body Biograph mMR system (Siemens, Erlangen, Germany). The CMR protocol comprised cine- and late-gadolinium-enhancement (LGE)-imaging. Metabolism was assessed with FDG-PET after oral glucose loading to effect myocardial carbohydrate uptake. PET was acquired for 65 min starting with tracer injection. Uptake values from 60 to 65 min p.i. were divided by the area under the blood activity curve and reported as percentages relative to the segment with maximal myocardial FDG uptake.ResultsA characteristic pattern of LGE in the LV lateral wall was observed in 13/14 patients whereas an additional septal LGE pattern was documented in 6/14 patients only. There was one patient without any LGE. Segmental FDG uptake was 88 ± 6% in the LV lateral wall vs. 77 ± 10% in the septal wall (p < 0.001). There was an inverse relationship between segmental FDG activity compared to segmental LGE extent (r = −0.33, p = 0.089). There were N = 6 LGE-positive patients with a segmental difference in FDG uptake of >15% in the LV lateral wall compared to the septal wall = ΔFDG-high group (lateral FDG = 91±3% vs. septal FDG = 69±8%; p < 0.001) while the remaining N = 7 LGE-positive patients showed a segmental difference in FDG uptake of ≤ 15% = ΔFDG-low group (lateral FDG = 85±7% vs. septal FDG = 83 ± 5%; p = 0.37). Patients in the ΔFDG-high group showed only a minor difference in the LGE extent between the LV lateral wall vs. septal wall (p = 0.09) whereas large differences were observed in the ΔFDG-low group (p < 0.004).ConclusionsSegmental FDG uptake—reflecting myocardial metabolic activity—is higher in the LV free wall of BMD patients—possibly due to a higher segmental work load. However, segmental metabolic activity seems to be dependent on and limited by the respective segmental extent of myocardial fibrosis as depicted by LGE-imaging.

Quantitative analysis of late iodine enhancement using dual-layer spectral detector computed tomography: comparison with magnetic resonance imaging.

To evaluate the segmental myocardial extracellular volume (ECV) fraction and to define a threshold ECV value that can be used to distinguish positive late gadolinium enhancement (LGE) segments from negative myocardial segments using dual-layer spectral detector computed tomography (SDCT), with magnetic resonance imaging (MRI) as a reference. Fifty-six subjects with cardiac disease or suspected cardiac disease, underwent both late iodine enhancement on CT (CT-LIE) scanning and late gadolinium enhancement on MRI (MRI-LGE) scanning. Each procedure occurred within a week of the other. Global and segmental ECVs of the left ventricle were measured by CT and MRI images. According to the location and pattern of delayed enhancement on MRI image, myocardial segments were classified into 3 groups: ischemic LGE segments (group 1), nonischemic LGE segments (group 2) and negative LGE segments (group 3). The correlation and agreement between CT-ECV and MRI-ECV were compared on a per-segment basis. Receiver operating characteristic (ROC) curve analysis was performed to establish a threshold for LIE detection. Among the 56 patients, 896 segments were analyzed, and of these, 73 segments were in group 1, 229 segments were in group 2, and 594 segments were in group 3. In segmental analysis, CT-ECV in group 3 (27.0%; 24.9-28.9%) was significantly lower than that in group 1 (33.2%; 30.7-36.3%) and group 2 (34.9%; 32.3-39.8%; all P<0.001). Good correlations were seen between CT-ECV and MRI-ECV for all groups (group 1: r=0.920; group 2: r=0.936; group 3: r=0.799; all P<0.001). Bland-Altman analysis between CT-ECV and MRI-ECV showed a small bias in all 3 groups (group 1: -2.1%, 95% limits of agreement -11.3-7.1%; group 2: -0.6%, 95% limits of agreement -13.1-11.9%; group 3: 1.0%, 95% limits of agreement -12.7-14.7%). CT-ECV could differentiate between LGE-positive and LGE-negative segments with 83.1% sensitivity and 93.3% specificity at a cutoff of 31%. ECV values derived from CT imaging showed good correlation and agreement with MR imaging findings, and CT-ECV provided high diagnostic accuracy for discriminating between LGE-positive and LGE-negative segments. Thus, cardiac CT imaging might be a suitable noninvasive imaging technique for myocardial ECV quantification.

Obstructive and Nonobstructive Hypertrophic Cardiomyopathy: Differences in Global and Segmental Myocardial Strain by Cardiac Magnetic Resonance Feature Tracking.

To evaluate any significant differences in myocardial strain between hypertrophic obstructive cardiomyopathy (HOCM) and nonobstructive ones (HNCM), as assessed by cardiac magnetic resonance feature tracking (CMR-FT). A total of 17 patients (mean age: 54±14 y) with echocardiographic diagnosis of HOCM (left ventricular outflow tract obstruction peak gradient ≥30 mm Hg), 19 patients (mean age: 49±16 y) with HNCM (peak gradient <30 mm Hg), and 18 age-matched and gender-matched healthy controls (mean age: 42±14 y). All patients underwent cardiac MRI with SSFP-cine to assess left ventricular global and segmental strain analysis by CMR-FT. Late gadolinium enhancement (LGE) sequences were used for semiautomatic quantification of LGE volume, mass, and percentage. The magnitude of global radial, circumferential, and longitudinal strain as well as strain rate were significantly lower in all patients in comparison to controls (P<0.001), except for radial and circumferential strain between HOCM and controls (P=0.270; P=0.154). The latter strain parameters were significantly higher in HOCM than HNCM (radial strain: 31.67±7.55 vs. 21.26±7.10, P<0.001; circumferential strain: -17.94±2.78 vs. -13.46±3.42, P<0.001). Radial and circumferential strain and circumferential diastolic strain rate were higher in mid-anterior (P<0.001), mid-anteroseptal (P<0.001), and all apical segments (P<0.005) between the 2 groups of patients. Moreover, longitudinal strain was higher only in apical segments in HOCM (P<0.02). HOCM patients showed higher left ventricular apical, mid-anterior, and mid-anteroseptal strain parameters compared with HNCM. These differences were independent of corresponding segmental thickness and LGE amount.

Correlation of Myocardial Strain and Late Gadolinium Enhancement by Cardiac Magnetic Resonance After a First Anterior ST-Segment Elevation Myocardial Infarction.

Objectives: To investigate the correlation of cardiac magnetic resonance (CMR) feature-tracking with conventional CMR parameters in patients with a first anterior ST-segment elevation myocardial infarction (STEMI).Methods: This sub-analysis of OCTAMI (Optical Coherence Tomography Examination in Acute Myocardial Infarction) registry included 129 patients who finished a CMR examination 1 month after a first anterior STEMI. Cine images were applied to calculate both global and segmental left ventricular peak strain parameters. The patients were divided into two groups by left ventricular ejection fraction (LVEF) and compared with 42 healthy controls. Segmental late gadolinium enhancement (LGE) was graded according to LGE transmurality as follows: (1) >0 to ≤ 25%; (2) >25 to ≤ 50%; (3) >50 to ≤ 75%; (4) >75%. Left ventricle was divided into infarcted, adjacent, and remote regions to assess regional function.Results: Compared with controls, global radial (28.39 ± 5.08% vs. 38.54 ± 9.27%, p < 0.05), circumferential (−16.91 ± 2.11% vs. −20.77 ± 2.78%, p < 0.05), and longitudinal (−13.06 ± 2.15 vs. −15.52 ± 2.69, p < 0.05) strains were impaired in STEMI patients with normal LVEF (≥55%). Strain parameters were strongly associated with LGE (radial: r = 0.65; circumferential: r = 0.69; longitudinal: r = 0.61; all p < 0.05). A significant and stepwise impairment of global strains was observed in groups divided by LGE tertiles. Furthermore, segmental strain was different in various degrees of LGE transmurality especially for radial and circumferential strain. Strains of adjacent region were better than infarcted region in radial and circumferential directions and worse than remote region in all three directions.Conclusion: Global and regional strain could stratify different extent and transmurality of LGE, respectively. Although without LGE, adjacent region had impaired strains comparing with remote region.

Hybrid CMR- and FDG-PET-imaging gives new insights into the relationship of myocardial metabolic activity and fibrosis in patients with Becker muscular dystrophy

Abstract Background Cardiac involvement in patients with Becker muscular dystrophy (BMD) is an important predictor of mortality. The cardiac phenotype of BMD patients is characterized by slowly progressive myocardial fibrosis that starts in the left ventricular (LV) free wall segments and extends into the septal wall during the disease course. Purpose Since the reason for this characteristic cardiac phenotype is unknown and comprehensive approaches using e.g. hybrid imaging combining cardiovascular magnetic resonance (CMR) with 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET) are limited, the present study addressed this issue by a comprehensive non-invasive imaging approach. Methods Hybrid CMR- and FDG-PET-imaging was performed in N=14 patients with BMD on a whole-body Biograph mMR system. The CMR protocol comprised cine- and late-gadolinium-enhancement (LGE)-imaging. Metabolism was assessed with FDG-PET after oral glucose loading to effect myocardial carbohydrate uptake. PET was acquired for 65 minutes starting with tracer injection. Uptake values from 60 to 65 minutes p.i. were divided by the area under the blood activity curve and reported as percentages relative to the segment with maximal myocardial FDG uptake. Results In the total study group, mean left ventricular (LV) ejection fraction (EF) was 55±5% and there were 6/14 patients with a reduced LV-EF &amp;lt;55%. A characteristic pattern of LGE in LV lateral wall was observed in 13/14 patients whereas an additional septal LGE pattern was documented in 6/14 patients only. Segmental FDG uptake was 88±6% in the LV lateral wall vs. 77±10% in the septal wall (p&amp;lt;0.001). There was a rather inverse relationship between segmental FDG activity compared to segmental LGE extent (r=−0.33, p=0.089). There were N=6 patients (= ΔFDG-high) with a segmental difference in FDG uptake of &amp;gt;15% in the LV lateral wall compared to the septal wall (lateral FDG = 91±3% vs. septal FDG = 69±8%; p&amp;lt;0.001) while the remaining N=8 patients (= ΔFDG-low) showed a segmental difference in FDG uptake of ≤15% (lateral FDG = 85±7% vs. septal FDG = 83±5%; p=0.37). Patients in the ΔFDG-high group showed a similar LV lateral wall vs. septal wall LGE extent of 12±6% vs. 7±15%, respectively, while those patients in the ΔFDG-low group demonstrated a large difference in LV lateral wall vs. septal wall LGE extent of 33±24% vs. 4±6%, respectively. Conclusions Segmental FDG uptake – reflecting myocardial metabolic activity – is in principal higher in the LV free wall of BMD patients – possibly due to a higher segmental work load. However, segmental metabolic activity seems to be dependent on and limited by the respective segmental extent of myocardial fibrosis as depicted by LGE-imaging. Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): Deutsche Gesellschaft für Kardiologie (DGK)

Examining the impact of inducible ischemia on myocardial fibrosis and exercise capacity in hypertrophic cardiomyopathy

Myocardial ischemia in hypertrophic cardiomyopathy (HCM) is associated with poor outcomes. Vasodilator stress cardiac magnetic resonance (CMR) can detect and quantitate inducible ischemia in HCM patients. We hypothesized that myocardial ischemia assessed by CMR is associated with myocardial fibrosis and reduced exercise capacity in HCM. In 105 consecutive HCM patients, we performed quantitative assessment of left ventricular volume and mass, wall thickness, segmental wall thickening percent, segmental late Gadolinium enhancement (LGE), and extracellular volume fraction (ECV). Time-signal intensity curves of first pass perfusion sequences were generated for each segment at stress and rest. A myocardial perfusion reserve index (MPRI) (stress/rest slope) was calculated. Patients who underwent an echocardiographic (n = 73) and cardiopulmonary exercise test (n = 37) within 30 days were included. The mean age was 53.2 ± 15.4 years; 60% were male, and 82 patients had asymmetric hypertrophy. Segments with end diastolic thickness ≥ 1.2 cm had a higher burden of LGE (4.1% vs 0.5% per segment), reduced MPRI (2.6 ± 1.5 vs 3.1 ± 1.8) and reduced thickening percent (48.9 ± 41.7% vs. 105.3 ± 59.5%), (P < 0.0001 for all comparisons). Patients with ischemia (any segment with MPRI < 2) were more likely to have dynamic left ventricular outflow tract (LVOT) obstruction (63.3% vs 36.7%, P = 0.01), to be smokers (17% vs 6.9%, P = 0.04), and had a higher ECV (30% vs 28%, P = 0.04). The total LGE burden was similar between the two groups (P = 0.47). Increasing ischemia burden (number of segments with MPRI < 2) was associated with worsened ventilatory efficiency (VE/VCO2) (P < 0.001) but not peak oxygen consumption or anerobic threshold (P > 0.2). In a patient-level multivariable logistic regression model, only LVOT obstruction remained a significant predictor of ischemia burden (P = 0.03). Myocardial ischemia by CMR is associated with myocardial segmental dysfunction and interstitial fibrosis, as assessed by ECV, in HCM patients, even in segments free of LGE. Conversely, quantitative ischemia burden was not associated with replacement fibrosis as assessed by total LGE burden. Patients with ischemia had greater prevalence of dynamic LVOT obstruction; and in a subset of patients with cardiopulmonary exercise testing, ischemia burden was associated with worsened ventilatory efficiency.

Differentiating Nonischemic Dilated Cardiomyopathy With Incidental Infarction From Ischemic Cardiomyopathy by Geometric Indices Derived From Cardiovascular Magnetic Resonance.

The purpose of this study was to differentiate nonischemic dilated cardiomyopathy with incidental myocardial infarction (NICM with incidental MI) from ischemic cardiomyopathy (ICM) by integrating left ventricular (LV) geometric indices and ischemic late gadolinium enhancement (LGE), obtained from cardiac magnetic resonance (CMR) imaging. All subjects were studied on a 1.5 Tesla magnetic resonance imaging scanner. All patients had an LV ejection fraction (LVEF) <50% with LV dilation. LV end-diastolic volume (LVEDV), LVEDV index (LVEDVi), LVEF, the number and distribution of ischemic LGE segments, and ratios of volumetric and functional indices to ischemic LGE segments were determined. Logistic regression was used to detect the independent predictor of ICM. Receiver operating characteristic analysis differentiated NICM with incidental MI from ICM. Of a total of 63 patients enrolled, 45 patients had ICM, and 18 patients had NICM with incidental MI. Both groups had similar LVEF. Compared with ICM, NICM with incidental MI had more LV dilation, whereas ICM had more ischemic LGE segments. A higher number of ischamic LGE segments remained an independent predictor of ICM (odds ratio: 18.2, 95% confidence interval: 1.64-201.34, P=0.018). The optimal cut-off value for detecting NICM with incidental MI is the ratio of LVEDVi to the number of ischemic LGE segments over 25 mL/m2/segment (sensitivity 100%, specificity 91%, P<0.0001). Patients with NICM with incidental MI can be reliably distinguished from ICM using the ratio of LVEDVi divided by the number of ischemic LGE segments. This technique may improve diagnosis and help aid management of patients with cardiomyopathy and coexistent coronary artery disease.