Late Gadolinium Enhancement Research Articles

Risk factor analysis of microvascular obstruction after percutaneous coronary intervention for ST-segment elevation myocardial infarction

ObjectiveThis study aimed to explore the risk factors of microvascular obstruction (MVO) after percutaneous coronary intervention (PCI) in patients with ST-segment elevation myocardial infarction (STEMI). Materials and MethodsA retrospective analysis was performed on 165 patients with STEMI who successfully underwent emergency PCI and completed cardiac magnetic resonance (CMR) within 1 week after PCI. Total ischemia time (symptom onset to wire, S2W), first medical contact to wire (FMC2W), and door to wire (D2W) were compared with the recommended critical time nodes for STEMI treatment. Left ventricular function was evaluated by CMR cine, and myocardial infarction characteristics and MVO were evaluated by late-gadolinium enhancement (LGE). Binary logistic regression analysis was used to evaluate the effect of delay in treatment of STEMI on the occurrence of MVO after PCI. ResultsIn this study, 89 (53.9%) patients with STEMI presented with MVO after emergency PCI. The FMC2W time and S2W time in the MVO (+) group were significantly longer than those in the MVO (−) group (P<0.05). Compared with the MVO (−) group, the MVO (+) group had larger myocardial infarction size (IS) and lower left ventricular ejection fraction (LVEF) (P<0.05). Patients with FMC2W time >120min and S2W time >300min had greater myocardial IS and MVO than the FMC2W ≤120min and S2W time ≤300min group, respectively. Logistic regression analysis showed that S2W time >300min (P=0.039, OR=2.756, 95% CI=1.053-7.213) was an independent predictor of MVO after PCI in patients with STEMI. ConclusionShortening the total time of myocardial ischemia and increasing the proportion of early reperfusion therapy can prevent or reduce MVO after PCI.

Atrial fibrillation substrate and impaired left atrial function: a cardiac MRI study.

Structural and fibrotic remodelling is a well-known contributor to the atrial fibrillation (AF) substrate. Epicardial adipose tissue (EAT) is increasingly recognized as a contributor through electrical remodelling in the atria. We aimed to assess the association of LA fibrosis and EAT with LA strain and function using cardiac magnetic resonance (CMR) imaging in patients with AF. LA fibrosis was assessed using late gadolinium enhancement CMR, LA EAT was assessed using the fat-water separation Dixon sequence, and feature tracking was applied to assess global longitudinal strain in its three components [reservoir (GLRS), conduit (GLCdS), and contractile (GLCtS)]. LA emptying fraction and LA volume were measured using the cine sequences. All CMR images were acquired in sinus rhythm. One hundred one AF patients underwent pre-ablation CMR (39% female, average age 62 years). LA fibrosis was negatively associated with the three components of global longitudinal strain (GLRS: R = -0.35, P < 0.001; GLCdS: R = -0.24, P = 0.015; GLCtS: R = -0.2, P = 0.046). Out of the different sections of the LA, fibrosis in the posterior and lateral walls was most negatively correlated with GLRS (R = -0.32, P = 0.001, and R = -0.33, P = 0.001, respectively). LA EAT was negatively correlated with GLCdS (R = -0.453, P < 0.001). LA fibrosis was negatively correlated with LA emptying fraction but LA EAT was not (R = -0.27, P = 0.007, and R = -0.22, P = 0.1, respectively). LA EAT and fibrosis were both positively correlated with LA volume (R = 0.38, P = 0.003, and R = 0.24, P = 0.016, respectively). LA fibrosis, a major component of the AF substrate, and EAT, an important contributor, are associated with a worsening LA function through strain analysis by CMR.

Magnetic Resonance Myocardial Imaging in Patients With Implantable Cardiac Devices: Challenges, Techniques, and Clinical Applications.

Cardiovascular magnetic resonance imaging (MRI) in patients with cardiac implants, such as pacemakers and defibrillators, has gained importance in recent years with the development of modern cardiac implantable electronic devices. The increasing clinical need to perform MRI examinations in patients with cardiac implants has driven the development of new advanced MRI sequences to mitigate image artifacts associated with cardiac implants. More specifically, advances in imaging techniques, such as wideband late gadolinium enhancement imaging, wideband T1 mapping, and wideband perfusion, have been designed to improve image quality and examinations in patients with cardiac implants, enabling a comprehensive and more reliable diagnosis, which was previously unattainable in these patients. This review article explores recent developments and applications of wideband techniques in the field of cardiovascular MRI, offering insights into their transformative potential. Clinical applications of wideband cardiovascular MRI are highlighted, particularly in assessing myocardial viability, guiding ventricular tachycardia ablation, and characterizing myocardial tissue.

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.

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&amp;lt;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&amp;lt;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&amp;lt;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&amp;lt;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&amp;lt;0.001; LR-test p&amp;lt;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

Subclinical myocardial fibrosis is almost ubiquitous in the hearts of older British persons: 'MyoFit46' cardiovascular sub-study of the NSHD

Abstract Background Unprecedented numbers are now surviving to older age, but little is known about the burden or pattern of myocardial fibrosis in the asymptomatic elderly population. Previous 1.5 Tesla (T) cardiovascular magnetic resonance (CMR) studies found a prevalence of unexpected infarct-pattern late gadolinium enhancement (LGE) of 17-20% above 75 years but less is known about non-infarct pattern scar in this group. We investigated the prevalence, patterns, and clinical predictors of left ventricular (LV) scar in a large asymptomatic older age cohort. Methods CMR with a single 3T magnet was performed on participants all born in the same week in March 1946, as part of the longest running continued surveillance birth cohort: the National Survey of Health and Development. LV short-axis stack LGE imaging was performed using a free-breathing motion-corrected balanced steady-state free precession sequence with phase-sensitive inversion-recovery. Two blinded observers independently recorded the prevalence, extent, and pattern of LGE per participant. Logistic regression was used to study the association between clinicodemographic parameters and LGE. Results 460 participants were prospectively recruited of which 406 completed CMR with LGE imaging (77.8 ± 0.1 years, 44% male). 341 (84%) demonstrated LGE affecting a mean of 2.1±1.2 myocardial segments per participant (Figure 1). The commonest pattern of LGE was inferior right ventricular insertion point (RVIP), observed in 66.9%. Other patterns included (Figure 2): Linear mid-wall (19.6%) of which 38% were located in the inferior/lateral walls; subepicardial (12.1%); subendocardial infarct-pattern (8.8%); patchy/diffuse (1.6%); embolic LGE (0.6%). Sub-analysis was performed comparing those without significant unexpected fibrosis (LGE–) vs those with focal fibrosis (LGE+, excluding RVIP and those participants with a known history of prior myocardial infarction). LGE+ participants were more likely to be female (71.7% vs 49.1%, p&amp;lt;0.001) or diabetic (11.3% vs 5.1%, p=0.05), had a higher body surface area (BSA, 1.9 vs 1.8 m2, p&amp;lt;0.001), weight (80.1 vs 72.8 kg, p&amp;lt;0.001), LV indexed end systolic volume (24.2 vs 20.4 ml/m2, p=0.001) and LV indexed mass (59.2 vs 55.4 g/m2, p&amp;lt;0.001), and a lower LV ejection fraction (67.9 vs 71.8%, p&amp;lt;0.001) In multivariable logistic regression: BSA, LV indexed mass, LV ejection fraction and diabetic status were independently associated with LGE+ status (odds ratios [95% confidence intervals]: 9.4 [0.7–3.8]; 1.0 [0.01–0.05]; 0.9 [-0.08--0.02]; and 2.5 [0.03–1.7] respectively, p&amp;lt;0.05). Conclusion Advanced PSIR MOCO LGE imaging at 3T reveals that the majority (84%) of asymptomatic British persons above the age of 75 harbour unexpected ‘subclinical’ focal fibrosis, with a substantial proportion of these scars consistent with probable historical myocarditis events. Further work will now explore the life-course determinants of this scar burden in the older age human heart.

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&amp;lt;0.001). The Cox &amp; 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&amp;lt;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

Prognostic impact of the concept of late gadolinium enhancement granularity in non-ischaemic dilated cardiomyopathy

Abstract Background The prognostic stratification of non-ischaemic dilated cardiomyopathy (DCM) to predict the risk of death is mainly driven by the left ventricular ejection fraction (LVEF). Indeed, LVEF&amp;lt;35% is currently the only indication for primary prevention with implantable cardioverter-defibrillator (ICD) in these patients. Beyond LVEF, several cardiac magnetic resonance imaging (MRI) studies have suggested the strong prgnostic impact of late gadolinium enhancement (LGE), and particularly its extent and location. Therefore, we assumed that a more granular approach combining detailed LGE findings including extent, location and pattern could improve risk stratification in this population. Purpose To assess the additional prognostic value of the concept of "Late Gadolinium Enhancement (LGE) Granularity" that includes extent, location, and pattern in non-ischaemic dilated cardiomyopathy (DCM) patients to predict all-cause death. Methods Between 2008-2021, all consecutive patients with DCM without ICD or history of sustained ventricular arrythmia referred for cardiac MRI were included in two French centres. In line with the current ESC and AHA guidelines, DCM was defined by the LV dilation and LVEF&amp;lt; 50% using cardiac MRI. All patients with history of coronary artery disease or clinical history of myocarditis were excluded. The primary outcome was all-cause death using the French National Registry of Death. Cox regressions were performed to determine the prognostic value of each LGE findings. The additional prognostic value of the LGE granularity was assessed by the C-statistic increment, the continuous net reclassification improvement (NRI), and the integrative discrimination index (IDI). Results Of 1,668 DCM patients (age 52±8 years, 54% males), 268 (16%) died after a median (interquartile range) follow-up of 9 (7-12) years. With a median LVEF value of 39% (30-46), 472 (28%) patients had non-ischemic LGE. Using survival curves, patients with LVEF&amp;gt;35% but the LGE septal location showed a higher risk of death compared to all patients with LVEF≤35% with or without LGE (except for the septal location, all p&amp;lt;0.001). In DCM patients with LGE (N=472), LGE extent (adjusted HR: 4.27, 95% CI: 2.22-8.22), septal location (HR: 5.74, 95% CI: 3.35-9.85) and multiple areas of LGE (HR: 4.38, 95% CI: 2.08-9.22; all p&amp;lt;0.001) were all independently associated with death after adjustment for prognosticators. The concept of "LGE granularity" combining all these LGE features showed the best improvement in model discrimination and reclassification over traditional prognosticators including LVEF (C-statistic improvement: 0.14; net reclassification improvement=64.3%; integrative discrimination index=29.0%; all p&amp;lt;0.05). Conclusion In a large cohort of DCM patients, the concept of "LGE granularity" combining LGE extent, location and the presence of multiple areas had an additional prognostic value above traditional prognosticators including LVEF to predict all-cause death.

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

Revisiting risk stratification in hypertrophic cardiomyopathy after the recent guidelines - LGE remains tough to beat

Abstract Background and Objectives Over the last decades, the recommendation for ICD implantation for the primary prevention of sudden cardiac death (SCD) in hypertrophic cardiomyopathy (HCM) has been evolving. Late gadolinium enhancement (LGE) has been incorporated in the guidelines as a risk factor to be considered for ICD implantation. The aims of this study were: 1) assess the evolution of accuracy and discriminative ability of the different guidelines (ESC 2014, ESC 2022, ESC 2023, ACC 2011 and ACC 2020) in predicting SCD; and 2) to understand whether LGE can further help in the risk stratification of SCD. Methods We conducted an international multicentric retrospective analysis of HCM patients undergoing cardiac magnetic resonance (CMR) for diagnostic confirmation and/or risk stratification. Eligibility criteria for ICD according to the ESC 2014 (HCM), ESC 2022 (Ventricular arrhythmias VAs), ESC 2023 (Cardiomyopathies), ACC 2011 and ACC 2020 (both HCM guidelines) was determined for each patient. Our primary endpoint was a composite of SCD, appropriate ICD discharge and sustained VT. Results We included a total of 530 patients (median age was 49 (IQR 35-61), 57% male). Over a median follow-up of 3.8 (IQR 1.6 – 7.0) years, 27 events occurred (13 SCDs, 8 appropriate ICD discharges and 6 sustained VAs). The diagnostic accuracy statistics of the European and the American societies guidelines have evolved similarly over time: sensitivity and PPV increased, NPV remained high and discriminative ability also increased (see Figure). However, the concordance in risk assessment is only moderate between the ESC 2022 and ACC 2020 (κ = 0.60 (95%CI: 0.54–0.67); p &amp;lt; 0.001) or the ESC 2023 and ACC 2020 guidelines (κ = 0.56 (95%CI: 0.49–0.62); p &amp;lt; 0.001). LGE was present in 80% of patients. Median LGE% was 3.2% (IQR 0.5 – 8.4%) and remained an independent predictor of arrhythmic events after adjustment to known confounders (aHR of 1.09 per 1% increase in LGE% [95% CI 1.05 – 1.12; p &amp;lt; 0.001]). The Youden test showed a best cut-off for LGE burden of 7.1%. Further risk stratification could be reached by employing LGE% as an arbiter. Irrespectively of the guideline publisher, in patients with any recommendation for ICD (classes IIa and IIb), the absence of LGE identified patients with no arrhythmic events during follow-up (see Figure). Conclusions Current guidelines have shown increased sensitivity, PPV and discriminative power when compared with older counterparts. LGE burden remains an independent risk factor for arrhythmic events and although extensive LGE burden has been included in the risk stratification for ICD implantation, further stratification can be accomplished for ICD recommendation, since this seems to be a predictor stronger than clinical parameters.

Myocardial scar in end-stage hypertrophic cardiomyopathy: correlation with systolic function and prognostic significance

Abstract Background Hypertrophic cardiomyopathy with systolic impairment, often referred to as end-stage HCM (ES-HCM), has a poor prognosis. Scar is a significant contributor but the patterns and prognostic significance are unknown. Aim To understand role of scar in ES-HCM and investigate potential predictors of outcome. Methods A retrospective 4 centre study of ES-HCM (LVEF≤55%) who had undergone CMR between 2006 and 2022 for unexplained LVH. Exclusion criteria were: scaring therapies (septal reduction), phenocopies (amyloidosis, storage) and dual pathologies (severe aortic valve disease, previous infarction). CMR followed standardized protocols. All images were core-lab analysed de-novo with scar quantified using the full width at half maximum technique for late gadolinium enhancement (LGE) quantification in grams (LGEm) and percentage of total LV mass (LGE%). Cox models used to identify risk factors for all-cause mortality. Results From 3810 HCM CMR scans, 128 were ES-HCM pts (3%), 25(20%) were excluded due to known infarction. 103 (male n=82, 81%; age 57yrs[IQR51–68]) formed the study cohort. Of the 54% genotyped, 62% carried a (likely)pathogenic sarcomere mutation: MYBPC3 (n=20), MYH7 (n=7), TNNT2 (n=4), TMP1 (n=2),ALPK3 (n=1). Heart morphology was: 38(37%) isolated basal septal hypertrophy, 30(29%) reverse septal curvature, 7(7%) mid-cavity LVH with apical aneurysm, 3(3%) apical HCM, 24%other. The median EF was 46%(IQR 39-50). In only one third (34%) the ventricle was dilated (LVEDd mean 97ml/m2 IQR 79-112). The RV was impaired in 19(18%). Median max wall thickness was 17mm(IQR15-20) and LVmass 74mg/Kg(IQR65-90). Scar was present in 94(93%) and was typically extensive: median LGE% 23%(IQR 13-33), LGEm 31g(IQR 16-45) – although 7% had no scar. The LGE pattern was diffuse in 38%, patchy in 35%, ring-like in 9%, and infarct-like in 7% (all without coronary narrowing at invasive/non-invasive coronary artery assessment). LGE and cardiac function were effectively independent with low or no correlation between scar and LVEF% or global longitudinal strain (r2=0.015,p=0.227 or r2= 0.048,p=0.028 for LGE% and LGEm against LVEF; r2=0.059,p=0.021 or r2=0.196,p&amp;lt;0.001 for LGE% and LGEm against GLS) with poor correlation also with indexed stroke volume. During a 5 year (IQR 3-7) follow-up (516patient-years), 30 deaths occurred: mean age at death was 62(52-74). Using multivariate Cox regression analysis EF and demographics such as age were not predictive, but LGE% (HR 1.046, 95%IC 1.007-1.086, p=0.019 and GLS (HR 1.172, 95%IC 1.004-1.368, p=0.044) were independent all-cause mortality predictors (C-index 0.708; table). Conclusion Myocardial scar is almost always present in ES-HCM and is typically extensive – but with some unexpected features: 7% of patients have no LGE, dual pathology(infarction) is not rare, and ringlike LGE (ALVClike) may occur. LGE correlates poorly with any measure of LV impairment but is a strong predictor of mortality, as is GLS.

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

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

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)&amp;lt;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&amp;lt;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&amp;lt;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&amp;lt;0.001) and the septal location (HR=6.65, 95% CI: 3.02-14.6, p&amp;lt;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.

Quantifying late gadolinium enhancement improved sudden cardiac death risk prediction in non-ischemic dilated cardiomyopathy

Abstract Background While previous studies have proved the late gadolinium enhancement (LGE) was associated with poor prognosis in non-ischemic dilated cardiomyopathy (DCM), the optimal method for LGE quantification and the ability of LGE extent in identifying sudden cardiac death (SCD) remain less clarified. Purpose This study sought to compare the reproducibility of LGE quantification methods and explore the asssociation between LGE extent and SCD endpoint in DCM patients. Methods In this prospective study, LGE was quantified by the 2-6 standard deviations (SD) above the remote myocardium and full-wide half-maximum (FWHM) methods. The primary endpoint was SCD and arrythmia endpoint included SCD and aborted SCD. Reproducibility of LGE quantification was measured by Bland-Altman analysis and intra-class correlation coefficients (ICC). Competing risk regression analysis, C-index and area under the curve (AUC) were performed to identify the prognostic value. Results Among the 770 patients, 336 (44%) patients had LGE. FWHM demonstrated the best reproducibility compared with other quantification methods (intraobserver variability: ICC = 0.94, mean bias: -0.43 ± 4.89%; interobserver variability: ICC = 0.90, mean bias: -2.65 ± 6.40%). After a median follow-up of 49 months, SCD occurred in 61 (8%) patients and arrythmia endpoint occurred in 87 (11%) patients. Among all quantification method, LGE extent measured by FWHM showed the highest predictive value of SCD (C index: 0.72) and arrythmia events (C index: 0.71) than other methods. In the competing risk analysis, LGE extent was independently association with SCD (Hazard ratio [HR] 1.05, 95% confidence interval [CI] 1.03 - 1.07, P &amp;lt; 0.001) and arrythmia endpoint (HR 1.05, 95% CI 1.03 - 1.06, P &amp;lt; 0.001). LGE extent &amp;gt;8% showed significantly higher risk of SCD and arrythmia endpoint than those with LGE extent ≤8% (P &amp;lt; 0.001). Incoporating LGE exent and 35% left ventricular ejection fraction (LVEF) significantly improved the SCD (C index: 0.74 vs 0.61, P &amp;lt; 0.001) and arrythmia endpoint (C index: 0.73 vs 0.59, P &amp;lt; 0.001) prediction compared with LVEF. Conclusions FWHM demonstrated best reproducibility and highest SCD prediction ability among LGE quantification methods. Adding LGE extent to LVEF significantly improved the predictive value of SCD and arrythmia endpoint.Figure 1

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.

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 &amp;lt; 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 &amp;lt; 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 (&amp;lt;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.

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

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

Characterization of myocardial ischemia-reperfusion injury in a pig model with novel CW T1r and RAFF2 MRI methods in 1.5T

Abstract Introduction Myocardial ischemia-reperfusion injury (IRI) occurs after myocardial infarction when reperfusion aggravates the initial damage in myocardium by vast infiltration of inflammatory cells and elevated oxidative stress in myocardium that may lead to cardiac remodeling, heart failure and even death [1]. Magnetic resonance imaging (MRI) can accurately determine the anatomy of the heart and to characterize myocardial tissue. Novel endogenous rotating frame MRI methods, including continuous wave (CW) T1r and relaxation along a fictitious field with rank 2 (RAFF2), have been shown to characterize MI and other CVD in mouse and human myocardium with high sensitivity and specificity [2,3]. CW T1r and RAFF2 contrasts are occurring during radio frequency (RF) pulse (in kHz range) making them to be sensitive to slow molecular motions [2]. Comparing to conventional endogenous T1 and T2 methods, these are occurring after the RF pulse (in Larmor frequency (MHz) range) and therefore, these are non-selectively sensitive to different correlation times [4]. Golden standard to image MI is to use contrast agent (CA) in late gadolinium enhancement (LGE) method [2,4]. Using CA has drawbacks and therefore, there is an urgent need for optimizing the endogenous MRI methods in clinical practice. Purpose To characterize myocardial IRI in a pig model and to determine the sensitivity of both novel and conventional cardiac MRI methods. Methods IRI operation was done in 7 pig (30-35 kg) by occluding the LAD with a balloon catheter for 50 minutes. Imaging was done with 1.5T (MAGNETOM Aera) at 3 days and 28 days after the operation. Pig hearts were imaged with conventional native T1, T2, LGE, and with novel CW T1r and RAFF2 methods in both time points. These were imaged before CA injection and LGE was done 25 minutes after CA injection. Relaxation time mappings were done in a pixel-by-pixel manner with monoexponentially fitting. Region-of-interest (ROI) analysis was done to determine the relaxation times in IRI and remote areas. LGE was used to confirm the IRI areas in the myocardium. Relative relaxation time difference (RRTD)-values were calculated with the function of (((Relaxation Time of IRI area) – (Relaxation Time of Remote Area))/ (Relaxation Time of Remote Area)) to determine the contrast difference between IRI and remote areas. Results Relaxation times were elevated in IRI areas compared to remote areas (Figure 1A). Novel rotating frame RRTD-values were significantly higher than RRTD-values in conventional methods. This means that novel methods have larger contrast difference between IRI and remote areas compared to conventional methods, which indicates that novel methods are sensitive to characterize IRI area (Figure 1B). The location of MI areas was similar in both novel rotating frame and conventional methods compared to LGE (Figure 2). Conclusion Novel rotating frame relaxation time methods are sensitive to characterize the IRI area in pig model.Relaxation times, RRTD-valuesRelaxation times maps and LGE

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&amp;lt;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&amp;lt;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.

Impaired myocardial energetics in both sarcomere positive and negative HCM are linked to arrhythmic risk

Abstract Background Impaired myocardial energetics play a pivotal role in the complex pathophysiology of hypertrophic cardiomyopathy (HCM), and are thought to be mediated by energy-costly sarcomeric mutations and mitochondrial dysfunction (1). Two thirds of HCM patients, however, do not possess pathogenic sarcomeric mutations (2) and instead develop the condition due to a combination of increased polygenic susceptibility and comorbidities. Whether energetic impairment, a target of novel HCM treatments (e.g., myosin modulators such as Mavacamten), similarly affects sarcomere mutation positive (Sarc+) and negative (Sarc-) HCM remains unclear, as does the association between impaired energetics and markers of arrhythmic risk such as hypertrophy severity, cardiac function and non-sustained ventricular tachycardia (NSVT). This study aimed to investigate differences in resting myocardial energetics between Sarc+ and Sarc- HCM by measuring the phosphocreatine-to-adenosine triphosphate (PCr/ATP) ratio using phosphorus magnetic resonance spectroscopy (31P-MRS) and explore the association between impaired energetics and markers of arrhythmic risk in HCM. Methods We recruited one hundred (100) participants (80 non-obstructive HCM patients and 20 age- and sex-matched controls). Myocardial energetics were assessed using 31P-MRS to measure the PCr/ATP ratio. Cardiac magnetic resonance (CMR) imaging including cine, T1 (ShMOLLI), quantitative pixel-wise perfusion mapping (3) and late gadolinium enhancement (LGE) imaging was also performed. In addition, HCM patients underwent 7-day ECG monitoring to document NSVT episodes (3 beats ≥120 bpm). Results HCM patients had impaired myocardial energetics (PCr/ATP ratio) relative to controls (HCM 1.64±0.36 vs controls 1.97±0.32 p&amp;lt;0.001). PCr/ATP ratios did not differ between Sarc+ and Sarc- HCM even after adjustment for confounders including age, hypertrophy and fibrosis burden (Sarc+ 1.64 [1.50-1.78] vs Sarc- 1.64 [1.52-1.77], p=0.993). PCr/ATP ratio showed no correlation with maximum wall thickness (p=0.257), left ventricular ejection fraction (p=0.727) or myocardial perfusion reserve (p=0.851), but did inversely correlate with global longitudinal strain (r=-0.3, p=0.025). Reduced PCr/ATP was associated with presence of fibrosis (LGE+ 1.58±0.35 vs LGE- 1.79±0.37 p=0.025) and with NSVT, independent of age or fibrosis burden (NSVT+ 1.54 [1.40-1.67] vs NSVT- 1.73 [1.62-1.86], p=0.046). Conclusion Myocardial energetics are similarly impaired in Sarc+ and Sarc- HCM, and are independently associated with impaired contractility, greater fibrosis severity and heightened arrhythmic risk. Our findings provide novel mechanistic insights into the potentially favourable response of HCM patients to energy-sparing myosin modulator therapies irrespective of genotype and highlight the potential for cardiac energetics to serve as a marker of arrhythmic risk.