Presence Of Late Gadolinium Enhancement Research Articles

Abstract 4135080: Relation of focal and diffuse myocardial fibrosis to left bundle branch block in patients with dilated cardiomyopathy and structurally normal heart

The role of fibrosis in etiology of left bundle branch block (LBBB) in still not defined. The aim of this study was to assess the relation of focal and diffuse LV fibrosis to LBBB in patients with dilated cardiomyopathy (DCM) and in patients with structurally normal heart. Materials and methods: 60 DCM with LBBB (DCM-LBBB group, 46.7% male, mean age 57[50;63] years), 50 non-LBBB DCM (78% male, mean age 43[32.3;54] years), 15 patients (53.3% male, mean age 39[28;50] years) with LBBB and no signs of structural heart disease and 10 healthy volunteers (HV) were included in the study. Endomyocardial biopsy (EMB) was performed in 15(24,6%) LBBB-DCM and 16(32%) non-LBBB DCM patients and allowed the quantification of collagen volume fraction (CVF, Fig.1A-D). All patients and HV underwent cardiovascular magnetic resonance (CMR) with late gadolinium enhancement (LGE) analysis. Obtained LGE LV images were post-proceed for core scar (CS) and gray zone (GZ) calculation and 3D reconstruction. Diffuse LV interstitial fibrosis was estimated on all LGE-CMR images with the novel introduced marker - diffuse intensity ratio (DIR). Results: DIR was validated on EMB samples: the percentage of CVF (8.2[4.6;10.8]%) correlated with the DIR value (0.71 ± 0.13) in the same segment (r=0.66, p<0.001, Fig.1E-F). The value of CVF (Fig1A-D) and LGE presence in the septum in both DCM groups (Fig2) was comparable (8.2[4.6; 10.3] versus 7.6[6.1;15.3]%, p=0.82 and 19 (31.7%) versus 17 (34%) patients in non-LBBB DCM group respectively, p=0.8) Moreover, the presence of LGE and midwall fibrosis in septum was not related to the QRS duration (p=0.93 and 0.59). In non-LBBB DCM patients the percentage of CS was significantly higher (4.0[1.55; 11.68]% versus 1.4[0.05;8.5]% in LBBB-DCM patients, p=0.047), whereas percentage of GZ and total fibrosis in both DCM groups was comparable (Fig.3A,B). DIR value was higher in patients with idiopathic LBBB than in HV (0.54±0.09 versus 0.34±0.1, p<0.001) while the percentage of GZ and CS was extremely low and did not differ from its amount in HV (Fig.3C,D). Conclusion: Neither focal (including midwall striae) nor interstitial fibrosis is associated with LBBB in patients with DCM. Diffuse inflammation in LBBB-DCM patients may contribute to the progression of systolic dysfunction but is not the reason for LBBB. The increased value of interstitial fibrosis in patients with LBBB may reflect latent diffuse process in myocardium inexorably leading to DCM development.

Abstract 4137534: Troponin Can Predict Late Gadolinium Enhancement on Cardiac MRI in COVID-19 Vaccine-Associated Myocarditis

Background/Aim: We previously reported that late gadolinium enhancement (LGE) on cardiac MRI (CMR) was as high as 82% in pediatric patients with COVID-19 vaccine-associated myocarditis (C-VAM) despite mild clinical symptoms and normal left ventricular function. As LGE can be a harbinger for future adverse events including arrhythmias, heart failure or sudden cardiac death, we sought to identify predictors for LGE in C-VAM, specifically assessing troponin as a screening marker for C-VAM patients at risk for myocardial scarring who could then be referred for a confirmatory CMR with LGE. Methods: In this longitudinal multicenter retrospective observational study across 38 U.S. member institutions of the M yocarditis A fter C OVID V accination (MACiV) study network, 333 patients with C-VAM based on CDC criteria were included from April 2021 to November 2022. Data collected included demographics, laboratory values, clinical and cardiac imaging characteristics and outcomes. Using logistic regression, troponin levels at presentation were assessed as a log transformed continuous variable and categorized into tertiles. Results: The C-VAM patients were predominantly white (67%) adolescent males (91%, 15.7± 2.8 years). There were 216/333 (65%) patients who had both a reported troponin value and had a CMR. On univariate analysis, elevated troponin increased the probability of having LGE (OR=1.29, 95% CI: 1.06, 1.58, p=0.012). Even after controlling for age, race, sex, number of vaccine doses and left ventricular ejection fraction (OR=1.32, 95% CI: 1.06, 1.65, p=0.013). Patients >15 years compared to those ≤15 years of age were 2.94 (95% CI: 1.28, 6.75, p=0.011) times more likely to have LGE at presentation. Patients with troponin levels in the highest tertile compared to lowest tertile were 2.66 times (95% CI: 1.04, 6.83, p=0.042) more likely to have LGE along with a greater involvement > 4 AHA myocardial segments with LGE (p=0.004) Conclusions: Higher troponin values are associated with presence of late gadolinium enhancement on cardiac MRI in patients with COVID-19 vaccine-associated myocarditis. Troponin levels at presentation may facilitate risk stratification and function as a screening tool to identify those C-VAM patients with the greatest likelihood of myocardial scarring, who may benefit from undergoing CMR for tissue characterization.

Abstract 4119554: Septal Thickness has a Variable Effect on Shock Incidence Rate by ICD Indication in Hypertrophic Cardiomyopathy.

Introduction: Hypertrophic cardiomyopathy (HCM) is the most common cardiomyopathy. People with HCM are at risk of cardiac arrest. ACC/AHA guideline-supported indications for ICD placement include cardiac arrest or VT, family history of sudden cardiac death in a close relative ≤50, massive septal hypertrophy (MSH - septal thickness ≥30mm), apical pouch, and non-sustained ventricular tachycardia (NSVT). Methods: People attending any Mayo Clinic site on > 1 occasion who underwent ICD placement for HCM who had documented cardiac magnetic resonance (CMR) results were included in the study from time of ICD placement to last device interrogation. Outcome was incidence rate of first appropriate shock. Multivariable cox regression was used to examine the association between septal thickness and shock rate, controlling for current age, sex and secondary vs primary prevention device. An interaction term for association between septal thickness and each ICD indication in turn was incorporated into regression, and stratum specific estimates produced using linear computation. Results: 326 people were included in the study, of whom 50 experienced at least one appropriate ICD shock over 1,487.95 person years (incidence rate 3.36 per 100 person years, NNT 29.76 per year). MSH was strongly associated with shock rate (HR 2.29 [1.19 to 4.40], p=0.013). In people without MSH, there was a 50% reduction in shocks where a subjective measure (syncope or family history of sudden cardiac death) was present (table 1). In this cohort, NSVT resulted in a threefold increase in incidence of shock (HR 3.15 [1.446 to 6.47], p=0.003). In the presence of MSH, there was a four-fold increase in shock rate in people who underwent ICD insertion for family history of sudden cardiac death or for syncope (table 2). There was no difference in shock rates in people with NSVT prior to ICD placement based on septal thickness (HR 0.76 [0.21 to 2.74], p=0.679). There was strong evidence of interaction between NSVT and MSH on shock rates (LR χ2 =6.94, p=0.008), such that presence of both risk factors did not increase shock rate. Concurrent presence of late gadolinium enhancement (LGE) >15% on CMR and MSH was associated with a significant increase in shock rate (3.58 [1.43 to 8.98], p=0.006). Conclusion: MSH is a helpful indicator of who will benefit from ICD placement among people with a pre-existing indication for a device, particularly among those with a more subjective indication for a device.

Propensity score-matched analysis in isolated left ventricular dilation and non-ischaemic dilated cardiomyopathy

Abstract Background The presence and extent of late gadolinium enhancement (LGE) assessed by cardiac magnetic resonance imaging (CMR) are strong prognosticators of death in patients with non-ischaemic dilated cardiomyopathy (DCM), defined by the current guidelines as left ventricular (LV) dilation and left ventricular ejection fraction (LVEF)<50%. Although the current guidelines defined the concept of "isolated LV dilation" as LV dilation with preserved LVEF≥50%, the prognostic value of the LGE granularity including its extent, location and pattern is not established in this population. Purpose To assess the prognostic value of the concept of "LGE granularity" including its extent, location, and pattern for predicting all-cause death above traditional prognosticators in patients with LV dilation and reduced LVEF (i.e. DCM) or preserved LVEF (i.e. isolated LV dilation), separately. Methods Between 2008 and 2021, all consecutive patients with DCM and isolated LV dilation without ICD or history of sustained ventricular arrhythmia referred for CMR were included in two centres. All patients with history of coronary artery disease or myocarditis were excluded. The primary outcome was all-cause death using the French National Registry of Death. A 1:1 propensity score matching was performed to balance baseline characteristics in patients with DCM vs. those with isolated LV dilation. Cox regressions were performed to determine the prognostic value of each LGE findings. Results Of 2,752 patients analysed (age 52±8 years, 56% male), 408 (15%) patients died after a median (interquartile range) follow-up of 9 (7-12) years. A total of 737 (27%) patients had LGE. Patients with DCM had a higher rate of death than patients with isolated LV dilation (16% versus 13%, p=0.02). In the propensity-score matched population (N=1,084 in DCM subgroup and N=1,084 in isolated LV dilation), the LGE presence was associated with death (HR=2.98, 95%CI: 1.97-4.50, p<0.001). In isolated LV dilation patients with LGE (N=265), the LGE extent (HR=1.41, 95%CI:1.09-1.83, p=0.009), the presence of LGE in multiple areas (HR=3.86, 95%CI: 1.73-8.61, p<0.001) and the septal location (HR=2.97, 95%CI:1.37-6.46, p=0.006) were strong prognosticators of death after adjustment for traditional prognosticators. Similarly, in DCM patients with LGE (N=268), the LGE extent (HR=1.42, 95% CI:1.07-1.89, p=0.014), the presence of LGE in multiple areas (HR=8.41, 95%CI: 3.32-21.3, p<0.001) and the septal location (HR=6.65, 95% CI: 3.02-14.6, p<0.001) were strongly associated with death after adjustment. Conclusion In a large cohort of DCM and isolated LV dilation patients, the concept of "LGE granularity" was independently associated with all-cause death after adjustment for all traditional prognosticators in both DCM and isolated LV dilation. These results suggest the existence of a continuum between isolated LV dilation and DCM, and that CMR assessment could improve the risk stratification in this population.

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.

Left atrial strain predicts adverse events in hypertrophic cardiomyopathy: preliminary results from a CMR study

Abstract Background Hypertrophic cardiomyopathy (HCM) is associated with an increased risk of major adverse cardiovascular events (MACE), however, current risk stratification methods are imperfect. Left atrial global longitudinal strain (LA GLS) is an increasingly acknowledged predictive parameter, yet its potential role in HCM is not well defined. Purpose This study aims to investigate the prognostic role of cardiac magnetic resonance (CMR)-derived LA GLS for the occurrence of MACE in patients with HCM. Methods A retrospective, single-centre, CMR study of HCM patients was conducted. Clinical data was collected from electronic medical record and CMR images were analysed by two blinded investigators. LA GLS was derived from CMR two-chamber cine images by a semiautomatic method, and was categorized according to its median value. The endpoint was a composite of MACE, including all-cause death, sudden cardiac death (SCD), sustained and non-sustained ventricular tachycardias (VT), appropriate implantable cardiac defibrillator (ICD) shocks, heart failure (HF) hospitalization, and new-onset atrial fibrillation (AF). Cox regression analysis was performed. The preliminary results of the study are now reported. Results A total of 54 HCM patients were included, mean age was 58.5 years ± 15.9 and 38.9% were female. Average maximal wall thickness (MWT) was 18.0 mm ± 3.9, 37% had left ventricular outflow obstruction (LVOTO) and 45.1% had positive late gadolinium enhancement (LGE). After a mean follow-up of 6.9 ± 3.0 years, 26 patients (48.1%) experienced the composite endpoint. Figure 1 shows the clinical and CMR differences according to the occurrence of MACE. LA GLS was significantly lower in patients with MACE compared to those without (26.5 ± 19% vs 36.7 ± 13%, p=0.026), with a moderate predictive value (AUC = 0.68, Figure 2A). Multivariate Cox regression analysis revealed that a decrease in LA GLS (HR 1.09 per each 1% decrease, 95% CI 1.03-1.15, p=0.002), the presence of LGE (HR 6.9, 95% CI 1.7-28, p=0.007), the presence of LVOTO (HR 3.4, 95% CI 1.12-10.2, p=0.031) and an increase in MWT (HR 1.23 per each 1mm increase, 95% CI 1.05-1.45, p=0.011) were independently associated with MACE. Among low-risk HCM patients (absence of LGE or LVOTO, or MWT below our median value), LA GLS had an additional prognostic role, and those with an LA GLS above the median value (LA GLS>29.7%) presented a remarkably favourable prognosis (Figure 2B-D). Conclusions CMR-derived LA GLS is a predictor of outcomes in HCM beyond established imaging prognostic factors. Particularly, LA GLS appears to be useful in risk-stratifying low-risk HCM patients: those with normal LA GLS show an excellent prognosis. If confirmed in larger studies, LA GLS could be used to individualise HCM management.Figure 2

Routine application of cardiac magnetic resonance imaging in patients with suspected myocarditis from immune checkpoint inhibitor therapy

Abstract Background Cardiovascular adverse events including myocarditis associated with immune checkpoint inhibitor (ICI) therapy remain a challenge in clinical practice. Diagnostic assessment of ICI-related myocarditis (ICI-M) is challenging due to a variable phenotype, confounding effects and limited sensitivity of diagnostic tools. Cardiac magnetic resonance imaging (CMR) is used to diagnose non-ICI myocarditis, but evidence on diagnostic sensitivity is low, particularly in patients with a discrete phenotype. Here, we aim to assess the impact of CMR in patients with suspected ICI-related myocarditis and relate to final diagnosis including endomyocardial biopsy findings. Methods All consecutive patients receiving CMR for suspected ICI-M between September 2019 and January 2024 were included and retrospectively analysed. CMR parameters were correlated with clinical, laboratory and echocardiographic parameters and stratified for presence or absence of myocarditis as per final diagnosis. Results A total of 55 patients who received CMR for suspected ICI-related myocarditis were analysed, including 25 patients with confirmed ICI-M as per final diagnosis and 30 patients with cardiotoxicity other than myocarditis or no cardiotoxicity (ICI-O). The mean age (ICI-M versus ICI-O) was 65.7±13.6 versus (vs.) 67.3±9.9 (p=0.61) years, 32.0% vs. 26.7% (p=0.67) were female, and 40.0% vs. 26.7% (p=0.29) had pre-existing coronary heart disease. Cardiac biomarkers and echocardiographic data did not differ between the groups. In CMR analysis, presence of late gadolinium enhancement (LGE) was associated with ICI-M (56.0% vs. 26.7%, p=0.027). Myocardial oedema was generally rare and not associated with ICI-M. Endomyocardial biopsy (EMB) was used in 6 out of 55 patients (10.9%) with suspected ICI-M. In 4 of these 6 patients (66.7%) EMB confirmed ICI-M diagnosis. Of note, only 2/4 patients with EMB-confirmed myocarditis showed abnormal CMR findings. Conclusion The diagnostic assessment of ICI-M is challenged by low sensitivity of common diagnostic measures, often requiring a multimodal approach. Presence of LGE in CMR was associated with ICI-M, but sensitivity and specificity are low. Our data emphasize the high value of EMB in patients with clinically suspected ICI-M despite inconspicuous CMR. Prospective data to improve diagnostic criteria are needed.

Incremental prognostic value of late gadolinium enhancement granularity in patients with hypertrophic cardiomyopathy

Abstract Background The prognostic stratification of hypertrophic cardiomyopathy (HCM) using cardiac magnetic resonance (CMR) is based on the extent of late gadolinium enhancement (LGE). To enhance risk stratification for sudden cardiac death (SCD), the ESC has recently added LGE extent in the guidelines, at ≥15% of LV mass. However, SCD has become an uncommon event in this population, and mortality is now mostly related to other phenotypes, such as atrial fibrillation, stroke, and heart failure. While previous studies have showed the prognostic value of LGE to predict all-cause mortality, the prognostic impact of additional LGE features is not well established. Therefore, we aimed to assess the incremental prognostic value of the granularity of LGE including extent, location, and pattern in patients with HCM to predict all-cause death. Methods Between 2008 and 2021, all patients referred for HCM assessment using CMR, without history of coronary artery disease (CAD) or clinical history of myocarditis were prospectively recruited in two French centers. The outcome was all-cause death using the French National Registry of Death. The concept of "LGE granularity" was defined as a comprehensive model combining all the following LGE features with extent (by segment), location (septal or others), and pattern (midwall and/or subepicardial). Using nested Cox proportional hazard models, the additional predictive value of LGE features was assessed by the C-statistic increment, the continuous net reclassification improvement (NRI), the integrative discrimination index (IDI) and the global Chi-2. Results Among the 2,672 included patients (52±7 years, 56% males), 862 (32%) had LGE. After a median (IQR) follow-up of 9 (7–11) years, 447 (17%) patients died. Survival curves show an increased risk for LGE presence (log-rank p<0.001, Figure 1A). After adjustment for traditional prognosticators in the overall population (N=2,672), the presence of LGE was strongly associated with all-cause death (adjusted hazard ratio (HR) 3.96, 95% CI: 3.26-4.80, p<0.001). In the subgroup of patients with LGE (n=862), survival curves showed that all parameters defining the LGE granularity were associated with a higher risk of all-cause death (all p<0.001, Figure 1B). A nested Cox model adjusted on traditional prognosticators showed that the LGE extent, location and pattern were all independently associated with all-cause death (all p<0.001, Figure 2). The model of "LGE granularity" combining all independently significative LGE features showed the best improvement in model discrimination and reclassification above traditional prognosticators (C-statistic improvement: 0.90; NRI=41.9%; IDI=13.2%, Chi-2 global=450, all p<0.001; LR-test p<0.001, Figure 2). Conclusion In a large cohort of HCM patients, the "LGE granularity" model combining the extent, location, and pattern of LGE had an incremental prognostic value over and above traditional prognosticators to predict all-cause death.Prognostic value of LGE granularityIncremental prognostic value LGE granula

Improving the yield of genetic testing in dilated cardiomyopathy using late gadolinium enhancement

Abstract Background Genetic testing has become an important tool in the work-up of dilated cardiomyopathy (DCM), aiding in family screening and providing information about prognosis and arrhythmic risk. Nonetheless, a significant proportion of patients with DCM present negative genetic test results. The "Madrid Score" was created to evaluate the likelihood of positive genetic tests and increase their yield in DCM patients. Purpose To determine if late gadolinium enhancement (LGE) assessment can improve the Madrid Score accuracy and increase the yield of genetic tests for DCM. Methods A single-centre retrospective study of patients diagnosed with DCM who underwent cardiac magnetic resonance (CMR) and genetic test between January 2017 and October 2023. The CMR imaging included the assessment of LGE. Multivariate logistic regression was performed and the model’s change in performance was evaluated when adding LGE. Results A total of 90 patients with the diagnosis of DCM underwent CMR and genetic test during the study period. Patient’s mean age was 51.0±14.6 years, and 57.1% were male. The genetic test was positive (G+) in 42 (46.7%), and negative (G-) in 48 (53.3%) patients. A variant of uncertain significance was present in 31 (34.4%), and these were included in the G- group. Most of the known independent predictors of a G+ given by the Madrid Score were significant in our cohort: Family history of DCM (OR: 4.82; CI: 1.73-11.60; p < 0.001), absence of hypertension (OR: 0.19; CI: 0.06-0.58; p < 0.001), absence of left bundle branch block (OR: 0.22; CI: 0.05-0.98; p = 0.047), and low electrocardiogram voltage in peripheral leads (OR: 3.13; CI: 0.87-11.26; p = 0.081). When analyzing the effect of LGE in the regression model (R2 = 0.622, p < 0.001), we found that the number of LGE segments (OR: 2.54; CI: 1.10-5.90; p = 0.031), and the presence of LGE in the anterior wall (OR: 3.01; CI: 1.42-12.04; p = 0.041), were associated with a higher rate of positive genetic tests. When comparing both regression models, the incorporation of LGE increased the prediction power of the standard Madrid Score, correctly predicting 82.0% of the tests in our sample, with a probability of a G+ result ranging from 2% when all predictors were absent to 84% when ≥6 predictors, including LGE, were present. Conclusion Our study suggests that LGE assessment may enhance the Madrid Score performance and consequently improve genetic testing decisions in DCM, potentially leading to better use of the limited resources in our health care system.

T2 mapping as a marker of active myocardial injury in Anderson-Fabry disease patients

Abstract Background In Anderson-Fabry Disease (AFD) with cardiac involvement, left ventricular hypertrophy (LVH) is often associated with myocardial scarring by cardiovascular magnetic resonance (CMR) late gadolinium enhancement (LGE) imaging. Myocardial inflammation, detected as increased T2 weighted/T2 mapping (T2m) signal, has also been reported, although its role in disease progression is still unclear. Purpose To investigate the relationship between T2m and LGE/LVH progression in AFD patients. Methods 67 paired CMR scans (1.5T) from 30 AFD patients were included. Three groups were defined according to LGE: no LGE at either scan (LGE-/-); LGE at baseline, unchanged at follow-up (LGE+/-); LGE at follow-up, appeared or increased compared to baseline (LGE+/+). T2m was measured in the infero-lateral basal segment in all scans; in LGE+ scans only, LGE was also manually contoured (ROI_LGE), and the ROI_LGE copied and pasted on the matching T2m image (T2m_ROI_LGE). See Figure 1. Troponin I (TnI) was also dosed at each scan. A univariate repeated measures analysis of variance was used to compare the groups and Tukey-Kramer correction was applied. Results As expected, the presence of LGE was strongly associated with older age, higher global and regional T2m, left ventricular (LV) mass and TnI values. As a novelty, in the LGE+/+ scans (scar appearance/progression) T2m in the ROI_LGE was higher than in the LGE+/- scans (scar unchanged) (p value 0.02). None of the other parameters, such as LV mass, TnI and global T2m values, differ between the the LGE+/+ compared to the LGE +/- group. See Table 1. Conclusions In our AFD patients’ cohort, scar progression was associated with focal increase in T2m values, i.e. T2m may identify patients with active myocardial injury. The potential implication on management/disease progression monitoring needs to be tested in future research, with longer follow-up. The role of sex, with females known to have higher average T2m values, will also need to be explored in a wider patient’s cohort.

Refining risk stratification in hypertrophic cardiomyopathy: the role of late gadolinium enhancement and syncope in predicting adverse outcomes

Abstract Background The presence of late gadolinium enhancement (LGE) on cardiac magnetic resonance imaging (MRI) is recognized as a significant marker of myocardial fibrosis and a predictor of adverse outcomes in hypertrophic cardiomyopathy (HCM). Nevertheless, the specific quantity of LGE that correlates with poor outcomes is still under debate. Therefore, this study sought to assess the combined impact of LGE presence and a history of syncopal events and its association with clinical prognosis. Methods Between May 2018 and June 2023, a total of 230 HCM patients was prospectively enrolled at our Medical University, a tertiary referral center. The primary endpoint was a composite of new-onset ventricular tachycardia (VT), appropriate ICD therapy, and all-cause mortality. Results Median age of enrolled patients was 56 (IQR 44-64) years and 40% (n=94) were female. Median interventricular septal thickness (IVS) was 21 (IQR 18–25) mm and 43 % (n=84) had significant left ventricular outflow tract obstruction (LVOTO). Over a median follow-up of 3.2 years, 30 patients (13%) met the composite endpoint. These patients had a significantly higher LGE quantity compared to the non-event group (1.1 % vs. % 9.0, P=0.012). An LGE threshold of 5.2% was identified as an optimal predictor of the composite endpoint, with an area under the curve of 0.72, which increased to 0.77 when including at least one syncopal event in medical history. LGE > 5.2% and/or syncope were independently associated with adverse outcomes after multivariable adjustment (Adj HR 7.26 [95%CI 2.54-20.72]). Furthermore, NTproBNP and hsTnT were associated with the presence of LGE or syncope (OR for a 1-unit increase in standardized log-transformed biomarker NTproBNP 3.35 [95%CI 1.42-10.85]; hsTnT 3.48 [95%CI 1.48-10.24], respectively). Interestingly, typically used variables for risk stratification, such as age, IVS or LVOT were not significantly associated with these cardiac biomarkers. Conclusion An extent of LGE > 5.2% and the history of at least one syncope are associated with unfavorable clinical outcomes in HCM patients. These findings call for detailed MRI appraisal and suggest adopting a holistic approach to accurately identify high-risk patients.

Regional cardiac denervation predicts sustained ventricular arrhythmias in non-ischemic cardiomyopathy patients without LGE on CMR imaging

Abstract Background In patients with non-ischemic cardiomyopathy (NICM) and no late gadolinium enhancement (LGE) on cardiac magnetic resonance (CMR), risk prediction for the occurrence of sustained ventricular arrhythmias (VA) is challenging. Global and regional sympathetic denervation has been associated with VA in patients with ischemic cardiomyopathy. Its prognostic relevance in NICM is unknown. Purpose To assess the risk prediction of sympathetic denervation for the occurrence of VA in NICM patients without LGE. Methods Consecutive patients from the ‘Leiden Nonischemic Cardiomyopathy Study’, who underwent programmed electrical stimulation, LGE-CMR and 123I- MIBG imaging between 2011-2018 were included. The presence of LGE and global and regional sympathetic denervation on 123I- MIBG was evaluated and patients were followed for occurrence of VA. Global denervation was assessed using the heart-to-mediastinum ratio. Regional denervation was evaluated by calculating the number of denervated segments (DS), the ratio of DS, the summed defect score and the weighted denervation size. Results Of 75 included patients (63 years [52-68], 79% male, LVEF 36% [27-44], 37% inducible for VA) 35 had no LGE. During 4.5±1.6 years follow-up, VA occurred in 8/35 (23%) patients without LGE and in 18/40 (45%) patients with LGE. Among patients without LGE, those with VA had greater regional sympathetic denervation (number of DS 8 [8-10] vs. 2 [1-5], P=0.004; ratio of DS 0.5 [0.5-0.7] vs. 0.2 [0.1-0.4], P=0.007; defect score 36 [31-41] vs. 18 [14-24], P=0.01; weighted denervation size 47 [39-53] vs. 22 [16-30], P=0.01). In univariable analysis the number of DS (HR 1.25, 95% CI 1.06–1.46, P=0.006) was associated with the occurrence of VA in patients without LGE. Denervation of ≥ 7 segments identified patients without LGE at risk for VA (AUC: 0.83, sensitivity: 88%; specificity: 89%). Among patients with LGE, innervation state was not associated with VA during follow-up. Conclusions In NICM patients without LGE the extent of regional denervation may contribute to risk stratification for VA.Graphical Abstract

Left atrioventricular coupling index is an independent associate of new-onset AF and stroke in hypertrophic cardiomyopathy: a CMR study

Abstract Background Left atrial (LA) dysfunction is an important marker of disease progression in hypertrophic cardiomyopathy (HCM). LA volumes and functional parameters are associated with new-onset atrial fibrillation (AF) and its complications including stroke. The association between left atrioventricular coupling (LACI), a parameter reflecting the contribution of the left ventricular and LA remodeling to LA dysfunction, with the occurrence of new-onset AF and stroke has not been evaluated. Aim To investigate the association between LACI and the occurrence of new-onset AF or stroke in patients with HCM. Methods In patients with an established diagnosis of HCM and cardiac magnetic resonance (CMR) data, LACI was calculated as the ratio between the LA and the LV end-diastolic volumes. New-onset AF or occurrence of stroke comprised the primary combined endpoint. Cumulative event-free survival rates for the occurrence of the primary endpoint were estimated with the population divided according to a LACI cut-off value of 40%. The association between clinical and CMR variables and the primary endpoint was assessed with univariable and multivariable Cox proportional hazard regression models. Results Of 114 patients with HCM, (mean age 54±16 years, 33 (29%) female, LV ejection fraction 67.0±8.4%), 71 patients (49%) had a LACI > 40% (left atrioventricular uncoupling). During a median follow-up of 4.1 (1.8-6.4) years, 19 (16.7%) patients experienced new-onset AF or stroke. Patients with preserved left atrioventricular coupling (LACI ≤ 40%) had a lower cumulative rate of events compared to those with left atrioventricular uncoupling (log-rank p=0.031, Fig. 1). LACI was independently associated with new-onset AF or stroke after adjusting by the presence of late gadolinium enhancement (LGE) sex and age (HR=23.27, p=0.016). Conclusions In patients with HCM, the presence of left atrioventricular uncoupling is independently associated with the occurrence of new-onset AF or stroke.

Volume-pressure loop hemodynamic characterization of pulmonary hypertension

Abstract Background Pulmonary hypertension (PH) includes a wide spectrum of pathologies with different pathological bases and a variety of clinical scenarios in which right ventricular (RV)-pulmonary artery (PA) coupling has relevant prognostic implications. Currently, diagnosis and hemodynamic severity of PH is typically based on mean pulmonary arterial pressure (mPAP), pulmonary capillary wedge pressure (PCWP), and pulmonary vascular resistance (PVR). However, this conception does not take into consideration the evolution of these parameters throughout the cardiac cycle. We hypothesized that not only the magnitude but also the dynamics over time plays an important role in RV adaptation to pressure overload (i.e., constant fixed resistances throughout the cycle will have a different impact than a fluctuating resistances). Purpose To assess PA hemodynamic patterns throughout the cardiac cycle and their association with RV remodelling, by combining right heart catheterization (RHC) and cardiac magnetic resonance imaging (CMR) data. Methods 66 patients with PH (38 women, aged 63.59±14.70years, BMI 28.49±6.21 kg.m2) who underwent RHC in the supine position with a 7.5-FrSwan-Ganz catheter under fluoroscopic guidance (37 precapillary, 17 combined pre-postcapillary, 12 isolated postcapillary PH) and CMR with flow-encoded phase-contrast sequence were included. Pressure and flow tracings at the level of the main PA were integrated to obtain volume-pressure loops throughout the cardiac cycle. The resulting patterns based on morphology (Image 1) and slope (Pattern 1 mean slope 16,11% vs Pattern 2 mean slope 10,37%) were analysed and classified into 2 groups: Pattern 1 and Pattern 2. RV end-systolic (iRVESV) and end-diastolic volumes (iRVEDV), RV ejection fraction, RV mass and presence of late gadolinium enhancement (LGE) at the RV insertion points were compared between groups using parametric and non-parametric tests. Results Patients with Pattern 1 showed significantly higher mPAP (46.03±11.62 vs. 35.77±8.10 mmHg) and iPVR (746.22±584.54 vs 319.56±306.21 dynes.s.cm-5.m2) and lower PCWP (11.8±7.6 vs 17.7±7.2 mmHg). Precapillary PH patients more frequently presented a Pattern 1 (n=27; 77.1% vs 10; 32.3%). In addition, patients with Pattern 1 had higher RV volumes (iRVEDV= 105.45±34.62 ml/m2 vs 84.22±35.0 ml/m2, p=0,002; iRVESV 65.05±27.59 ml/m2 vs 44.63±25.09 ml/m2, p=0,001), poorer RV function (RVEF 39.81±11.33% vs 48.96±10.90%; p=0,001), larger RV mass (27.95±9.46 vs 23,44±7.46 g/m2, p=0,045) and smaller left atrial size (24.18±11.47 vs 34.06±19.15 cm2, p<0,001) than patients with Pattern 2. The quantification of LGE was also higher in Pattern 1 as compared with Pattern 2 (5.4±2.4% vs 3.0±2.3%, p<0.001). Conclusion Volume-pressure loops at the level of the main PA may differentiate patterns of PA hemodynamic fluctuations that have different impact on RV performance regardless the PH severity within the wide spectrum of PH.Volume-pressure loop patterns

Using deep learning to predict cardiovascular magnetic resonance findings from echocardiography videos

Abstract Background Echocardiography is the most common modality for assessing cardiac structure and function. While cardiac magnetic resonance (CMR) imaging is less accessible, CMR can provide unique tissue characterization including late gadolinium enhancement (LGE), T1 and T2 mapping, and extracellular volume (ECV) which are associated with tissue fibrosis, infiltration, and inflammation. While deep learning has been shown to uncover findings not recognized by clinicians, it is unknown whether CMR-based tissue characteristics can be derived from echocardiography videos using deep learning. Purpose To assess the performance of a deep learning model applied to echocardiography to detect CMR-based parameters. Methods In a retrospective single-center study, adult patients with CMRs and echocardiography studies within 30 days were included. A video-based convolutional neural network was trained on echocardiography videos to predict CMR-derived labels including WMA presence, LGE presence, and abnormal T1, T2 or ECV across echocardiography views. The model performance was evaluated in a held-out test dataset not used for training. Results The study population included 1,453 adult patients (mean age 56±18 years, 42% female) with 2,556 paired echocardiography studies occurring on average 2 days after CMR (interquartile range 2 days prior to 6 days after). The model had high predictive capability for presence of WMA (AUC 0.873 [95%CI 0.816-0.922]), however, the model was unable to reliably detect the presence of LGE (AUC 0.699 [0.613-0.780]), native T1 (AUC 0.614 [0.500-0.715]), T2 0.553 [0.420-0.692], or ECV 0.564 [0.455-0.691]). Conclusions Deep learning applied to echocardiography accurately identified CMR-based WMA, but was unable to predict tissue characteristics, suggesting that signal for these tissue characteristics may not be present within ultrasound videos.Central Figure -Study Pipeline-

The relationship between serum lumican levels and myocardial fibrosis in patients with hypertrophic cardiomyopathy

Abstract Background Hypertrophic cardiomyopathy (HCM) is the leading cause of sudden cardiac death in young individuals and an important cause of heart failure at any given age. Lumican, is an indicator of fibrosis and has been studied in various cardiac conditions. In this study, we aimed to evaluate the relation between serum Lumican levels and presence and extent of myocardial fibrosis in HCM. Methods The patients diagnosed with HCM between June 2022 and March 2023 were enrolled consecutively in this prospective study. Age and gender-matched healthy individuals formed control group. Additionally, HCM patients divided into two groups according to extent of late gadolinium enhancement (LGE). Results A total of 114 patients (62.3% male, 54.5±9.4 mean age) were enrolled in this prospective study. 64 patients formed HCM (+) and 50 patients formed HCM (-) group. The HCM (+) group is divided into two groups as LGE (+) and LGE (-) according to LGE involvement. Serum Lumican [p=0.018, β: 1.561, OR (95% CI): 1.080-2.257], NT-proBNP [p=0.043, β: 1.209, OR (95% CI): 1.079-2.527] and maximum wall thickness (MWT) [p=0.033, β: 1.322, OR (95% CI): 1.023-1.707] were revealed as independent risk factors associated with LGE by multivariate logistic regression analysis (Figure 1). ROC curve analysis was performed to identify the optimal cut-off value and calculate area under the curve (AUC) for Lumican, troponin (Tn) and NT-proBNP in order to predict the presence and extent of LGE in patients with HCM. A cut off value of 9.06 for Lumican was associated with 67.8% sensitivity and 65.5% specificity in prediction of LGE. A cut-off value of 932.4 for NT-proBNP was associated with 60% sensitivity, 60% specificity in prediction of LGE. Conclusion Myocardial fibrosis is one of the important mechanisms in HCM pathophysiology. Although LGE on cardiac magnetic resonance imaging(CMR) allows comprehensive evaluation of myocardial fibrosis, the support of diagnosis with a biomarker would be beneficial in clinical practice.Our study revealed that serum Lumican level is an independent predictor of severe LGE in HCM patients. Lumican can be used in addition to CMR for evaluating extence of myocardial fibrosis in HCM patients and may help clinicians in guiding follow-up and treatment.

Improving prognostic accuracy in ischemic cardiomyopathy: the CMR-LGE score

Abstract Background There is a need for accurate prognostic stratification tools in patients with ischemic cardiomyopathy (ICM). Several studies have shown the considerable impact of cardiac magnetic resonance (CMR) imaging findings notably late gadolinium enhancement (LGE) but an easy interpretable score to guide clinical practice is lacking. Purpose To determine the CMR parameters most predictive of mortality in a cohort of ICM patients with left ventricular ejection fraction (LVEF) less than 50%, and then to develop a readily interpretable score based on these parameters. Methods Between 2008 and 2022, all consecutive patients with a history of ICM with LVEF<50% and presence of ischemic LGE on viability CMR examination, were recruited by two independent centers. The primary outcome was all-cause death using French National Registry of Death. The first center (N=2,900) was designated as the derivation cohort for variable selection and score development, and the second center (N=691) was used as the validation cohort to evaluate the performance of the final score. Thirty-two variables (17 clinical and 15 CMR) were initially assessed. Automatic feature selection was performed using a machine-learning approach with a Random Survival Forest (RSF) algorithm. Using the selected variables, our proposed score, the CMR-LGE score, was derived from coefficients of the Cox regression. Performance evaluation on the validation cohort was conducted using Harrel’s C index compared with traditional prognostic factors associated with poor outcomes in ICM. Categories for the prognostic score were identified using a survival conditional inference tree analysis on the derivation cohort, aiming to maximize the log-rank score. Results Among the 3,591 patients included (mean age 65±12 years; 75% male; mean LVEF 44±6%), 549 (15.3%) died over a median follow-up of 9 (interquartile range: 7–12) years. Feature selection with RSF highlighted that the most important variables to predict death were LGE variables: the extent, the location (septal and anterior) and the transmurality of ischemic LGE as well as the extent of additional midwall LGE (Figure 1). Following these findings, we developed the CMR-LGE score by rounding the coefficient of a Cox regression (Figure 2A). Harrel’s C index of CMR-LGE score outperformed traditional prognostic factors, including LVEF (0.88 vs 0.69). Finally, based on our CMR-LGE score, we identified a low-risk population (CMR-LGE score below 6) and a high-risk population (CMR-LGE above 8), validated using survival curves in the validation cohort (Figure 2B). Conclusion Using RSF, we identified that the 5 most important CMR variables to predict mortality in ICM were all LGE features. Our CMR-LGE score showed excellent performance to stratify patient risk compared to traditional prognostic factors including LVEF.Variable selectionModel building and evaluation

Predictive value of cardiac 18F-fluorodeoxyglucose positron emission tomography for fatal ventricular arrhythmic events in patients with cardiac sarcoidosis

Abstract Background Patients with cardiac sarcoidosis (CS) face an elevated risk of fatal ventricular arrhythmic events (FVAE), including sudden cardiac death. Late gadolinium enhancement (LGE) from contrast-enhanced cardiac magnetic resonance is used for diagnosis of CS and estimation of FVAE risk. However, its application is limited in cases with cardiac devices, renal failure or contrast agent allergies. 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) emerges as a diagnostic tool for CS, even in cases where LGE is not feasible. Purpose This study aimed to investigate the potential utility of FDG-PET in predicting FVAE in patients with CS by hypothesizing that higher or lower percent FDG uptake could predict the FVAE risk. Methods Cardiac FDG-PET data from 121 patients with CS, acquired at our university hospital between March 2008 and November 2020, were analyzed. A polar-map model was used to calculate percent uptake relative to maximal cardiac FDG uptake in each of the American Heart Association (AHA) 17 segments (Figure A). Percent uptakes of the AHA 17 segments were compared between groups with and without future FVAE. LGE information was available in 82 patients and was used to assess the presence of LGE in regions where percent FDG uptake differed between the two groups. Results Among enrolled patients (mean age 59.5 ± 10.0 years, 67.8% women), 43 experienced FVAE following FDG-PET image acquisition. The group with future FVAE had a higher history of FVAE (7.7% vs. 37.2%) and beta-blocker administration (38.5% vs. 60.5%), larger left ventricular diastolic diameter (LVDd) (49.3 ± 7.3 mm vs. 57.4 ± 9.5 mm) and lower ejection fraction (LVEF) (56.6 ± 13.6% vs. 42.0 ± 15.2%) compared to the group without it (P < 0.05 all). Percent FDG uptake in the basal interventricular septum part (segment 3) (Figure A) was lower in patients with future FVAE compared to those without it (54.4 ± 13.8% vs. 41.8 ± 15.2%, P < 0.001 corrected for multiple comparisons). Kaplan-Meier analysis with a median split of percent FDG uptake in segment 3 showed that patients with lower uptake (<49%, N= 62) had lower FVAE-free survival compared to those with higher uptake (≥49%, N = 59) (P = 0.007) (Figure B). A Cox hazard model also demonstrated an association between percent FDG uptake in segment 3 and FVAE onset (hazard ratio 0.972 [95% CI 0.951, 0.995], P = 0.015) after adjusting for previous FVAE, beta-blocker administration, LVDd and LVEF. Similarly, analysis within the subgroup with LGE in the septum (N = 58) revealed a higher risk of FVAE in the group with lower percent FDG uptake compared to those with higher uptake (P = 0.020) (Figure C(a)). However, this association was not evident in patients without LGE in the septum (N = 24) (P = 0.821) (Figure C(b)). Conclusions Reduced percent FDG uptake with LGE in the basal intraventricular septum may serve as a valuable predictor of future FVAE occurrence in patients with CS.

Three-dimensional deformation imaging to detect myocardial scar

Abstract Introduction Myocardial scar or fibrosis has significant implications in patient management and prognosis. Currently, cardiovascular magnetic resonance (CMR) is the reference technique for detection and quantification of scar though other imaging modalities have been proven to be useful as well. Purpose This study aims to investigate the usefulness of 3D strain echocardiography to identify myocardial scar in patients with ischaemic and non-ischaemic myocardial fibrosis using late gadolinium enhancement (LGE) CMR as a reference. Methods 149 individuals with ischaemic (89), non-ischaemic scar (26) and no scar (34) on LGE CMR underwent 3D transthoracic echocardiography. The 3D data sets were processed with the 4D LV analysis tool by TOMTEC Imaging Systems GmbH, Germany. The longitudinal, circumferential, radial, and principal tangential strain were calculated. Using a 16 LV-segment model the areas of LGE were assessed on CMR images, and a correlation between 3D strain values and LGE was investigated. Results A multivariate binary logistic regression model was built with the conditional backward elimination method using LGE as the dependent variable. The predictors made a significant contribution to the model (Wald test: 49.985, p<0.001). The Cox & Snell R-square was 0.141, and Nagelkerke R-square was 0.232, suggesting that the final model explains 14.1% or 23.2% of LGE variability. By logistic regression analysis, less negative peak principal tangential strain (P-PTS), peak circumferential strain (P-SC), and end-systolic circumferential strain (ES-CS) increased the odds, whereas increased peak radial strain (P-RS) decreased the likelihood of LGE (Table 1). The LGE extent was calculated as the average LGE transmurality of all 16 segments and was used as the dependent variable in linear regression models. The LGE extent was significantly correlated with all strain indices (Table 2). By stepwise linear regression analysis, P-PTS (B=0.029, 95%CI:0.019-0.040, P<0.001) outperformed the remaining strain variables in terms of linear association with LGE extent. Association between strain indices and the presence or absence of myocardial fibrosis in each of the 16 segments was tested by point biserial correlation (Table 3). PTS and CS indices were associated with myocardial fibrosis in 10/16 segments; RS indices were associated with LGE in 9/16 segments, and LS was not related to the presence of LGE in 15/16 segments. Septal (basal-mid-apical) and mid/apical anterior and inferior segmental strain showed more consistent associations with corresponding myocardial fibrosis. Conclusion 3D strain echocardiography is a promising and easily accessible technique, that can be used to identify areas of myocardial scar as it correlates well with LGE in many LV segments. Echocardiography is a bedside and widely available technique, and it could be used in patients with contraindications or no access to CMR or myocardial perfusion scan.Table 3

Systemic inflammation is associated with myocardial fibrosis in patients with obstructive hypertrophic cardiomyopathy.

Chronic low-grade inflammation, often observed in hypertrophic cardiomyopathy (HCM), promotes adverse ventricular remodelling. This study aimed to investigate the relationship between inflammatory markers and myocardial fibrosis (MF) in patients with HCM. This study included 102 patients with complete baseline data who underwent septal myectomy. Myocardial samples were stained with Masson's trichrome and analysed to determine myocardial collagen content and MF levels. Plasma levels of inflammatory markers were measured using standard laboratory procedures. Univariate and multivariate logistic regression analyses were performed to explore the relationship between the inflammatory markers and MF. Among the 102 participants included in the analysis, the mean age was 48.9years, with 69 [67.6%] being men. The overall MF ranged from 2.5% to 40.7% (mean=15.2±8.1%, median=13.0%, IQR=9.9%-18.4%). Participants were divided into two groups based on a median MF of 13%. The high MF group had a larger left atrial diameter and left ventricular ejection fraction. Levels of interleukin (IL)-2, tumour necrosis factor (TNF)-α and interferon (IFN)-α were significantly higher in patients with high MF compared to those with low MF (2.3 vs. 4.0pg/mL, 3.1 vs. 3.9pg/mL, 4.2 vs.4.7pg/mL, respectively; all P<0.05). In multivariate models adjusted for age, sex and other clinical features, IL-2, IL-5 and TNF-α, were correlated with increased interstitial MF [odds ratio (OR): 1.54, 95% confidence interval (CI): 1.10-2.14; OR: 1.42, 95% CI: 1.02-1.98; OR: 1.33, 95% CI: 1.04-1.70]. After additional adjustment for imaging indicators, IL-2 and TNF-α remained significant (OR: 1.49, 95% CI: 1.06-2.09, P=0.021; OR:1.35, 95% CI: 1.01-1.80, P=0.044). The correlation analysis between inflammation and replacement fibrosis assessed by CMR in 97 patients revealed that 72 (74.2%) showed late gadolinium enhancement (LGE). No significant correlation was found between inflammatory markers and the presence or extent of LGE. Higher levels of IL-2 and TNF-α were associated with increased histopathological interstitial MF in patients with HCM. Given the gradual progression of MF in HCM, initiating anti-inflammatory treatment in the early stages may delay its progression.