Cardiac resynchronization therapy (CRT) guidelines are based on clinical trials with limited female representation and inconsistent left bundle branch block (LBBB) definitions. Conventional QRS duration (QRSd) criteria show variable diagnostic accuracy between sexes, partly due to differences in heart size and remodelling. We evaluated the influence of sex, heart size, LBBB, and conduction delay on QRSd and assessed the diagnostic performance of conventional and indexed QRSd criteria using a population-based modelling approach. Simulated QRSd were derived from electrophysiological simulations conducted in 2627 UK Biobank healthy participants and 359 patients with ischaemic heart disease, by modelling LBBB and normal activation combined with/without conduction delay. QRSd criteria under-selected LBBB females and over-selected non-LBBB patients. Indexing by LVEDV and LV mass reduced sex disparities but increased the over-selection in non-LBBB patients. Height-indexed QRSd effectively resolved sex differences and maintained low non-LBBB selection rates, demonstrating superior performance and potential for more equitable CRT selection. These results uncover a key mechanistic driver of sex differences in LBBB detection that may contribute to CRT outcomes and underscore the importance of incorporating sex-specific considerations into updated CRT guidelines to ensure equitable and effective treatment.

Large-cohort imaging and diagnostic studies often assess cardiac function but overlook underlying biological mechanisms. Cardiac digital twins (CDTs) are personalized physics-constrained and physiology-constrained in silico representations, uncovering multi-scale insights tied to these mechanisms. In this study, we constructed 3,461 CDTs from the UK Biobank and another 359 from an ischemic heart disease (IHD) cohort, using cardiac magnetic resonance images and electrocardiograms. We show here that sex-specific differences in QRS duration were fully explained by myocardial anatomy while their myocardial conduction velocity (CV) remains similar across sexes but changes with age and obesity, indicating myocardial tissue remodeling. Longer QTc intervals in obese females were attributed to larger delayed rectifier potassium conductance G KrKs . These findings were validated in the IHD cohort. Moreover, CV and G KrKs were associated with cardiac function, lifestyle and mental health phenotypes, and CV was also linked with adverse clinical outcomes. Our study demonstrates how CDT development at scale reveals biological insights across populations.

Direct-to-patient platforms can overcome geographic and capacity barriers to rare-disease research, supporting inclusive and scalable recruitment. The Heart Hive was developed to enable nationwide, genomics-integrated cardiomyopathy research and rapid patient–study matching through a digital, patient-centred platform. Adults self-reporting a diagnosis, or inherited risk, of cardiomyopathy enrolled online, completed electronic consent, and provided baseline and longitudinal data for study matching. Participants in the pilot Cardiomyopathy Study were invited to return saliva kits by post for central cardiomyopathy-panel sequencing. Engagement and platform development were supported through formal patient and public involvement and partnership with Cardiomyopathy UK. Feasibility of digital recruitment, retention, and genomic validation was assessed. 338 participants met eligibility; 227 (67%) completed baseline surveys, 195 (86%) returned saliva kits, and 174 were sequenced (98 DCM, 76 HCM). Follow-up survey completion among sequenced participants was 83%. The cohort was 57% female, median age 57.5 years, and 98% White European; 78% had never previously participated in cardiovascular research. Genetic architecture was comparable to a clinic-recruited cohort (DCM 34.7% vs 30.6%; HCM 44.7% vs 38.2%), and actionable variants were identified in 17% of DCM and 29% of HCM participants opting for personal results. Self-reported recruitment accurately identifies cardiomyopathy cohorts equivalent in genetic composition to clinic-ascertained populations. The Heart Hive demonstrates a decentralised, re-contactable, and registry-ready digital model for nationwide precision-cardiology research.

Introduction Obesity is a common comorbidity and a risk factor for developing heart failure (HF). However, more data is required to understand the association between obesity and prognosis in specific patient subgroups. We sought to evaluate the effect of obesity on clinical phenotype and cardiovascular mortality in patients with non-ischaemic dilated cardiomyopathy (DCM). Methods This was a prospective observational cohort study of patients with DCM referred for a cardiovascular magnetic resonance (CMR) scan. Body mass index (BMI) was ascertained at enrolment. Patients were classified as normal weight (BMI <25), pre-obese (BMI 25–30) or obese (BMI >30). Patients underwent long-term clinical follow up. The primary endpoint was cardiovascular (CV) death. Cause of death was adjudicated by a panel of experienced cardiologists using death certificates and autopsy reports. Adjudicators were blinded to obesity status. Cumulative incidence curves were fitted using Kaplan-Meier method and compared using log-rank test. The association between obesity status and the primary endpoint was examined using univariable and multivariable Cox proportional hazard modelling. Results Of 727 patients with DCM (472 [65.2%] male, mean age 54.6 [±14.2] years and median LVEF 40% [29–49]), 239 (32.9%) were normal weight, 288 (39.6%) were pre-obese and 200 (27.5%) were obese. Obese and pre-obese patients had higher NYHA class than normal weight patients (p=0.003) and a higher proportion were treated with beta blockers, mineralocorticoid receptor antagonists and loop diuretics (p=0.01, p=0.001 and p=0.001 respectively). Absolute LV end-diastolic volume, LV end-systolic volume, RV end-diastolic volume and RV end-systolic volume were lowest in normal weight patients and highest in obese patients. However, there was no difference in LVEF (p=0.64) or RVEF (p=0.39) between weight classes. There was also no difference in the prevalence of myocardial replacement fibrosis between weight groups (p=0.99). After a median follow up of 7.7 years, 71 (9.8%) patients died from CV causes. Obesity was associated with a higher cumulative incidence of CV death compared to pre-obesity and normal weight (log rank p=0.02, figure 1). After adjusting for established prognostic markers including age, sex, LVEF, NYHA class, myocardial fibrosis presence, LAVi and RVEF, obesity remained independently associated CV death compared to normal weight (HR 2.00, 95% confidence interval [CI] 1.06–3.79), whereas pre-obesity was not associated with excess risk compared to normal weight (HR, 1.07, 95% CI 0.58–2.41) (combined p value = 0.03). Conclusions Obesity is associated with increased CV mortality in patients with DCM, despite having no demonstrable effect on phenotypic characteristics associated with prognosis, such as LVEF or myocardial fibrosis prevalence. Recent advances in pharmacological weight loss therapies may offer novel targeted therapeutic avenues to improve cardiovascular outcomes for obese patients with DCM. Conflict of Interest Nil

Introduction A subset of patients with dilated cardiomyopathy (DCM) undergo substantial left ventricular reverse remodelling with guideline-directed therapies to the point of normalisation of cardiac size and LVEF. However, it is unclear whether such patients have residual subclinical phenotypic abnormalities compared to healthy volunteers. Materials and Methods The REMIT-DCM study (Reverse remodelling and remission markers in the serial evaluation of DCM) was a prospective single-centre observational cohort study including patients with recent-onset DCM and age-/sex-matched healthy volunteers (HVOLs). Patients with DCM underwent CMR at baseline, 3-months and 12-months. Clinical remission from DCM was defined at 12-months if indexed LV end-diastolic volume (LVEDVi) had normalised, LVEF had risen by ≥10% to LVEF ≥50%, NT-proBNP had fallen below 250ng/L and symptom had resolved (NYHA class I). Results Of 70 patients with DCM (mean age 52±15 years, 79% men, baseline mean LVEF 30%), 67 completed the study and 21 (31%) were in clinical remission at 12-months (DCM-remission). Compared to HVOLs, patients with DCM-remission had lower 12-month LVEF (58±5 vs 65±4%, p<0.001), impaired LV strain (GLS/GCS/GRS: all p<0.001) and higher LVEDVi (p=0.03) and LVESVi (p<0.001). No difference in RV volumes or RVEF were observed, although those with DCM-remission had lower RV GLS than HVOLs (p=0.03). Patients with DCM-remission had higher LV mass index than HVOLs due to 30% greater extracellular matrix mass and 6% greater cellular mass. Of the patients with DCM-remission, 50% had late gadolinium enhancement, predominantly involving the mid-wall and septum. Higher native T1 (p=0.02) and a trend towards higher ECV values (p=0.06) were observed in DCM-remission patients compared to HVOLs. No difference in T2 was observed between groups. Discussion Despite apparent reversal of gross morpho-functional abnormalities, the DCM-remission phenotype remains distinguishable from HVOLs using CMR, with subclinical contractile dysfunction of both ventricles and increased LVMi driven by increased extracellular mass and, to a lesser degree, increased cellular mass. Replacement fibrosis persists in remission and is a common finding despite its association with adverse outcomes. Parametric mapping indicates residual interstitial fibrosis but not myocardial inflammation. Conclusion Patients with DCM-remission have important residual structural, functional and myocardial abnormalities despite marked clinical improvement. These may predispose to future disease relapse. Acknowledgements We thank the Royal Brompton and Harefield Cardiovascular Research Centre nurses and support staff.

Background and Aims Microstructural disturbances underlie dysfunctional contraction and adverse left ventricular (LV) remodelling after ST-elevation myocardial infarction (STEMI). Biphasic diffusion tensor cardiovascular magnetic resonance (DT-CMR) quantifies dynamic reorientation of sheetlets (E2A) from diastole to systole during myocardial thickening, and markers of tissue integrity [mean diffusivity (MD) and fractional anisotropy (FA)]. This study investigated whether microstructural alterations identified by biphasic DT-CMR: (i) enable contrast-free detection of acute myocardial infarction (MI); (ii) associate with severity of myocardial injury and contractile dysfunction; and (iii) predict adverse LV remodelling. Methods Biphasic DT-CMR was acquired 4 days (n = 70) and 4 months (n = 66) after reperfused STEMI and in healthy volunteers (HVOLs) (n = 22). Adverse LV remodelling was defined as an increase in LV end-diastolic volume >= 20% at 4 months. MD and FA maps were compared with late gadolinium enhancement images. Results Widespread microstructural disturbances were detected post-STEMI. In the acute MI zone, diastolic E2A was raised and systolic E2A reduced, resulting in reduced E2A mobility (all P < .001 vs. adjacent and remote zones and HVOLs). Acute global E2A mobility was the only independent predictor of adverse LV remodelling (odds ratio .77; 95% confidence interval .63-.94; P = .010). MD and FA maps had excellent sensitivity and specificity (all > 90%) and interobserver agreement for detecting MI presence and location. Conclusions Biphasic DT-CMR identifies microstructural alterations in both diastole and systole after STEMI, enabling detection of MI presence and location as well as predicting adverse LV remodelling. DT-CMR has potential to provide a single contrast-free modality for MI detection and prognostication of patients after acute STEMI.

AIMS:This study aimed to compare the association between measures of left atrial (LA) structure and function, derived from cardiovascular magnetic resonance (CMR), with cardiovascular death or non-fatal heart failure events in patients with non-ischaemic dilated cardiomyopathy (DCM). METHODS AND RESULTS:CMR studies of 580 prospectively recruited patients with DCM in sinus rhythm [median age 54 (interquartile range 44-64) years, 61% men, median left ventricular ejection fraction 42% (30-51%)] were analysed for measures of LA structure [LA maximum volume index (LAVImax) and LA minimum volume index (LAVImin)] and function (LA emptying fraction, LA reservoir strain, LA conduit strain (LACS), and LA booster strain]. Over a median follow-up of 7.4 years, 103 patients (18%) met the primary endpoint. Apart from LACS, each measure of LA structure and function was associated with the primary endpoint after adjusting for other important prognostic variables. The addition of each LA metric to a baseline model containing the same important prognostic covariates improved model discrimination, with LAVImin providing the greatest improvement [C-statistic improvement: 0.702-0.738; χ2 test comparing likelihood ratio P < 0.0001; categorical net reclassification index: 0.210 (95% CI 0.023-0.392)]. Patients in the highest tercile of LAVImin had similar event rates to those with persistent atrial fibrillation. Measures of LA strain did not enhance model discrimination above LA volumetric measures. CONCLUSION:Measures of LA structure and function offer important prognostic information in patients with DCM and enhance the prediction of adverse outcomes. LA strain was not incremental to volumetric analysis for risk prediction.

Introduction Improvements in cardiac magnetic resonance (CMR) have enabled better phenotyping of the left atrium (LA). However, little is known of the incremental prognostic value of the novel LA measurements (phasic LA strain, LA ejection fraction [LAEF], and LA minimum volume [LAVImin]) compared to LA maximum volume [LAVImax] in dilated cardiomyopathy (DCM). Thus, we decided to evaluate the prognostic value of each LA measure in DCM. Materials and Methods CMR studies of 580 DCM patients, in sinus rhythm, prospectively enrolled into a biobank between 2009 and 2017 were used. The primary endpoint was a composite of cardiovascular (CV) mortality and non-fatal major heart failure (HF) events, which included HF hospitalisations, heart transplantation or Left Ventricular (LV) assist device implantation. Event rates were compared between patients in sinus rhythm and those with persistent atrial fibrillation (AF). Results Over a median follow-up duration of 7.4 years (IQR 4.7–9.3), 103 patients (18%) met the primary endpoint. On univariable Cox regression analysis, all LA metrics were significantly associated with the primary endpoint (all, p<0.05). All indices, apart from LA conduit strain, remained associated with the endpoint on multivariate analyses adjusted for age, sex, NYHA, LV ejection fraction and the presence of fibrosis (all, p<0.05). The addition of the LA metrics to a baseline model containing conventional risk predictors improved model discrimination, with LAVImin providing the greatest improvement (C-statistic 0.702 to 0.738), similar to that of LAVImax (C-Statistic: 0.702 to 0.732) and LAEF (C-Statistic: 0.702 to 0.734). LA strain variables did not improve baseline model discrimination over LA volumes. Patients in the highest tercile of LAVImin had similar event rates to those with persistent atrial fibrillation. Discussion In line with previous studies, LA structure and function was independently associated with CV death and HF events. LA volumes and LAEF provided better prognostication than LA strain. Amongst the volumes, LAVImin improved baseline model discrimination better than LAVImax, perhaps because it reflects both LA structure and function. This is important as LAVImin can easily be added to CMR reporting protocols. Conclusion LA metrics provide incremental prognostic information in DCM patients. LA strain did not provide any additional prognostic information over LA volumes. Acknowledgements We would like to thank the Royal Brompton and Harefield Cardiovascular Research Centre nurses and support staff.

AimsTo characterize the phenotype, clinical outcomes and rate of disease progression in patients with early-stage non-ischaemic cardiomyopathy (early-NICM).Methods and resultsWe conducted a prospective observational cohort study of patients with early-NICM assessed by late gadolinium enhancement cardiovascular magnetic resonance (CMR). Cases were classified into the following subgroups: isolated left ventricular dilatation (early-NICM H-/D+), non-dilated left ventricular cardiomyopathy (early-NICM H+/D-), or early dilated cardiomyopathy (early-NICM H+/D+). Clinical follow-up for major adverse cardiovascular events (MACE) included non-fatal life-threatening arrhythmia, unplanned cardiovascular hospitalization or cardiovascular death. A subset of patients (n = 119) underwent a second CMR to assess changes in cardiac structure and function. Of 254 patients with early-NICM (median age 46 years [interquartile range 36-58], 94 [37%] women, median left ventricular ejection fraction [LVEF] 55% [52-59]), myocardial fibrosis was present in 65 (26%). There was no difference in the prevalence of fibrosis between subgroups (p = 0.90), however fibrosis mass was lowest in early-NICM H-/D+, higher in early-NICM H+/D- and highest in early-NICM H+/D+ (p = 0.03). Over a median follow-up of 7.9 (5.5-10.0) years, 28 patients (11%) experienced MACE. Non-sustained ventricular tachycardia (hazard ratio [HR] 5.1, 95% confidence interval [CI] 2.36-11.00, p < 0.001), myocardial fibrosis (HR 3.77, 95% CI 1.73-8.20, p < 0.001) and diabetes mellitus (HR 5.12, 95% CI 1.73-15.18, p = 0.003) were associated with MACE in a multivariable model. Only 8% of patients progressed from early-NICM to dilated cardiomyopathy with LVEF <50% over a median of 16 (11-34) months.ConclusionEarly-NICM is not benign. Fibrosis develops early in the phenotypic course. In-depth characterization enhances risk stratification and might aid clinical management.

Background Myocardial fibrosis (MF) forms part of the arrhythmic substrate for ventricular arrhythmias (VAs). Objectives This study sought to determine whether total myocardial fibrosis (TF) and gray zone fibrosis (GZF), assessed using cardiovascular magnetic resonance, are better than left ventricular ejection fraction (LVEF) in predicting ventricular arrhythmias in patients with nonischemic cardiomyopathy (NICM). Methods Patients with NICM in a derivation cohort (n = 866) and a validation cohort (n = 848) underwent quantification of TF and GZF. The primary composite endpoint was sudden cardiac death or VAs (ventricular fibrillation or ventricular tachycardia). Results The primary endpoint was met by 52 of 866 (6.0%) patients in the derivation cohort (median follow-up: 7.5 years; Q1-Q3: 5.2-9.3 years). In competing-risks analyses, MF on visual assessment (MFVA) predicted the primary endpoint (HR: 5.83; 95% CI: 3.15-10.8). Quantified MF measures permitted categorization into 3 risk groups: a TF of >0 g and <= 10 g was associated with an intermediate risk (HR: 4.03; 95% CI: 1.99-8.16), and a TF of >10 g was associated with the highest risk (HR: 9.17; 95% CI: 4.64-18.1) compared to patients with no MFVA (lowest risk). Similar trends were observed in the validation cohort. Categorization into these 3 risk groups was achievable using TF or GZF in combination or in isolation. In contrast, LVEF of <35% was a poor predictor of the primary endpoint (validation cohort HR: 1.99; 95% CI: 0.99-4.01). Conclusions MFVA is a strong predictor of sudden cardiac death and VAs in NICM. TF and GZF mass added incremental value to MFVA. In contrast, LVEF was a poor discriminator of arrhythmic risk.

Abstract Background The TRED-HF trial (1) found that 44% of patients with recovered dilated cardiomyopathy (DCM) relapsed in the short term after withdrawal of medical therapy. The longer-term risk of relapse is uncertain. Purpose This follow-up aims to investigate the longer-term risk of relapse in patients with recovered DCM and any possible predictive factors. Methods TRED-HF trial participants were followed until May 2023. The primary outcome was DCM relapse defined as >10% reduction in left ventricular (LV) ejection fraction to <50%, doubling in N-terminal pro-B-type natriuretic peptide (NT-pro-BNP) to >400ng/L, or clinical recurrence of heart failure (HF). Therapy intensity for HF was calculated using QUAD scores. The incidence of relapse was calculated using Kaplan-Meier estimates. Predictors of relapse were investigated using Cox proportional hazard modelling. Results For all fifty-one patients, median follow-up from enrolment was 6 (IQR: 6-7) years. Overall, thirty-three patients (65%) relapsed with an estimated 5-year relapse rate of 61% (95% CI 45-73). Twenty patients relapsed during the randomised trial, nine of whom had a recurrent relapse during follow-up (Figure 1). Thirteen patients relapsed for the first time after completion of the trial; of those, one patient did not have therapy withdrawn during the trial, 8 had restarted low intensity HF therapy and 4 patients stayed on no therapy. Five patients stayed off HF therapy and did not relapse. The overall mean intensity of HF therapy was lower after the trial compared to enrolment (mean difference in QUAD score -6 [-8 to -4]; p<0.001). A mean reduction in medication intensity was also seen at the point of relapse during the trial and during follow-up (Figure 2). Of relapses during follow-up, seven had identifiable triggers (arrhythmia (n=4), pregnancy (n=1), hypertension (n=1), infection (n=1)). Patients taking more HF medications at baseline or with higher baseline NT-pro-BNP were more likely to relapse. Corrected atrial fibrillation was associated with reduced future risk of relapse. Conclusions In patients with recovered DCM, the risk of relapse after therapy withdrawal increased with longer follow-up. Lower doses of HF medications and recurrent external triggers contributed to relapse. Few patients who stopped medications had sustained remission. Recovery of DCM after correction of AF was associated with a low risk of relapse provided atrial fibrillation did not recur.

AIMS:In TRED-HF, 40% of patients with recovered dilated cardiomyopathy (DCM) relapsed in the short term after therapy withdrawal. This follow-up investigates the longer-term effects of therapy withdrawal. METHODS AND RESULTS:TRED-HF was a randomized trial investigating heart failure therapy withdrawal in patients with recovered DCM over 6 months. Those randomized to continue therapy subsequently withdrew treatment between 6 and 12 months. Participants were recommended to restart therapy post-trial and were followed until May 2023. Clinical outcomes are reported in a non-randomized fashion from enrolment and from the end of the trial. The primary outcome was relapse defined as ≥10% reduction in left ventricular ejection fraction to <50%, doubling in N-terminal pro-B-type natriuretic peptide to >400 ng/L, or clinical features of heart failure. From enrolment to the last follow-up (median 6 years, interquartile range 6-7), 33 of 51 patients (65%) relapsed. The 5-year relapse rate from enrolment was 61% (95% confidence interval [CI] 45-73) and from the end of the trial was 39% (95% CI 19-54). Of 20 patients who relapsed during the trial, nine had a recurrent relapse during follow-up. Thirteen relapsed for the first time after the trial; seven had restarted low intensity therapy, four had not restarted therapy and two did not have therapy withdrawn. The mean intensity of therapy was lower after the trial compared to enrolment (mean difference -6 [-8 to -4]; p < 0.001). One third of relapses during follow-up had identifiable triggers (arrhythmia [n = 4], pregnancy [n = 1], hypertension [n = 1], infection [n = 1]). Corrected atrial fibrillation was associated with reduced risk of relapse (hazard ratio 0.33, 95% CI 0.12-0.96; p = 0.042). CONCLUSIONS:The risk of relapse in the 5 years following the TRED-HF trial remained high. Restarting lower doses of heart failure medications at the end of the trial, external triggers and disease progression are likely to have contributed to relapse.

Abstract Background Serial multiparametric cardiovascular magnetic resonance (CMR) in patients undergoing coronary artery bypass grafting (CABG) may provide mechanistic insight into dynamic and persistent abnormalities of the myocardium in patients with stable coronary artery disease (CAD). Objectives To assess for dynamic CMR markers of myocardial hypoperfusion and cardiac remodelling in patients undergoing CABG. Methods Patients with CAD awaiting elective CABG were recruited into an observational cohort study. Baseline evaluation included bloods, Seattle Angina Questionnaire-7, and adenosine stress perfusion CMR. Automated fully quantitative stress and rest myocardial blood flow was calculated, alongside assessment of the visual ischaemic burden. Native and post-contrast septal T1 indices were also measured. Repeat evaluation at 6-12 months post CABG was performed. Results Of 43 patients who underwent serial evaluation with CMR (mean age 62.1±9.3, median LVEF 68% [IQR: 62-73%]), there was improvement in the median visual ischaemic burden (18% [IQR: 11-21] vs 42% [IQR: 27-51], P<0.001), mean global stress myocardial blood flow (1.5±0.5 ml/min/g vs 1.3±0.5 ml/min/g, P=0.002) and median global myocardial perfusion reserve (2.4 [IQR: 1.7-2.8] vs 1.7 [IQR: 1.4-2.2], P=0.002) following CABG. Greater improvement in the SAQ-7 summary score was associated with a larger visual ischaemic burden at baseline (ρ=0.44, P=0.004) and a greater decrease in the visual ischaemic burden following CABG (ρ=-0.38, P=0.02). Quantitative MBF metrics did not associate with baseline or change in SAQ-7 summary score. Mean LV extracellular matrix volume decreased following CABG (16.6±3.6ml/m2 vs 18.2±4.6ml/m2, P=0.009). Conclusion Multiparametric CMR identifies dynamic changes in markers of myocardial perfusion and interstitial fibrosis in patients following CABG. Visual assessment of inducible myocardial hypoperfusion may identify patients who will derive the most symptomatic benefit from CABG. The results, however, suggest an important degree of residual inducible ischaemia and an unclear clinical role for CMR-derived MBF calculations.Serial CMR perfusion dataAssociation of SAQ with perfusion

AIMS:To assess whether left ventricular (LV) global longitudinal strain (GLS), derived from cardiovascular magnetic resonance (CMR), is associated with (i) progressive heart failure (HF), and (ii) sudden cardiac death (SCD) in patients with dilated cardiomyopathy with mildly reduced ejection fraction (DCMmrEF). METHODS AND RESULTS:We conducted a prospective observational cohort study of patients with DCM and LV ejection fraction (LVEF) ≥40% assessed by CMR, including feature-tracking to assess LV GLS and late gadolinium enhancement (LGE). Long-term adjudicated follow-up included (i) HF hospitalization, LV assist device implantation or HF death, and (ii) SCD or aborted SCD (aSCD). Of 355 patients with DCMmrEF (median age 54 years [interquartile range 43-64], 216 men [60.8%], median LVEF 49% [46-54]) followed up for a median 7.8 years (5.2-9.4), 32 patients (9%) experienced HF events and 19 (5%) died suddenly or experienced aSCD. LV GLS was associated with HF events in a multivariable model when considered as either a continuous (per % hazard ratio [HR] 1.10, 95% confidence interval [CI] 1.00-1.21, p = 0.045) or dichotomized variable (LV GLS > -15.4%: HR 2.70, 95% CI 1.30-5.94, p = 0.008). LGE presence was not associated with HF events (HR 1.49, 95% CI 0.73-3.01, p = 0.270). Conversely, LV GLS was not associated with SCD/aSCD (per % HR 1.07, 95% CI 0.95-1.22, p = 0.257), whereas LGE presence was (HR 3.58, 95% CI 1.39-9.23, p = 0.008). LVEF was neither associated with HF events nor SCD/aSCD. CONCLUSION:Multi-parametric CMR has utility for precision prognostic stratification of patients with DCMmrEF. LV GLS stratifies risk of progressive HF, while LGE stratifies SCD risk.

Introduction Many patients with dilated cardiomyopathy (DCM) undergo improvement in left ventricular ejection fraction (LVEF). Although DCM with improved LVEF (DCMimpEF) is associated with favourable clinical outcomes, cases of sudden cardiac death (SCD) have been reported in this population. Myocardial fibrosis, detected by late gadolinium enhancement (LGE) on cardiovascular magnetic resonance (CMR) is associated with SCD in patients with DCM with impaired systolic function, including those with mildly reduced LVEF; whether this association exists in patients with DCMimpEF has not been specifically evaluated. We sought to identify the incidence and determinants of SCD events in patients with DCMimpEF. Methods This was a prospective observational cohort study of patients with DCM referred for a CMR. Inclusion criterion was a confirmed diagnosis of DCM with a previously recorded LVEF <40% that had subsequently improved to LVEF ≥40% on the study enrolment CMR. Patients underwent long-term clinical follow up. The primary endpoint was a composite of SCD or aborted SCD (aSCD). aSCD was defined as either an appropriate ICD shock for a ventricular arrhythmia, or a non-fatal episode of ventricular fibrillation (VF) or spontaneous sustained ventricular tachycardia (VT) causing hemodynamic compromise and requiring cardioversion. All potential arrhythmic events were reviewed by a panel of experienced cardiologists, including a cardiologist with expertise in implantable cardiac devices. Adjudicators were blinded to clinical and CMR data. Cumulative incidence curves were fitted using Kaplan-Meier method and compared using log-rank test. The association between patient characteristics and the primary endpoint was examined using univariable Cox proportional hazard modelling. Results The study cohort comprised 141 patients with DCMimpEF (63.8% male, median age 56 years [interquartile range 44–64], median improved LVEF at enrolment 48% [44–52]). Most patients were NYHA class 1 or 2 (87%). A high proportion were treated with ACE inhibitors or angiotensin receptor blockers (88%) and beta blockers (75%); a modest proportion were treated with mineralocorticoid receptor antagonists (36%). Late gadolinium enhancement was present in 49/141 patients (35%). Over a median follow up of 7.8 years, 7 patients (5%) experienced SCD events. This included 3 patients who survived resuscitated VF/VT cardiac arrests and 4 patients who had appropriate ICD shocks for VT/VF. The presence of LGE on CMR was associated with a higher cumulative incidence of SCD/aSCD (log rank p=0.03, figure 1). No other variables were associated with SCD/aSCD in patients with DCMimpEF. Conclusions Despite improved cardiac function and low symptom burden, a small proportion of patients with DCMimpEF remain at risk of SCD. The presence of LGE does not preclude LVEF improvement but does render patients with DCMimpEF at higher risk of incident SCD events. These data support long-term clinical follow up of patients with DCM beyond the point of LVEF improvement. Our findings lend further support for the use of CMR for arrhythmic risk stratification in DCM and call into question the continued reliance on LVEF to determine ICD candidacy in this population. Conflict of Interest Nil

Abstract Background Myocardial fibrosis (MF) is an essential component of the arrhythmic substrate for ventricular arrhythmias (VAs). Aims To determine whether total myocardial fibrosis (TF) and gray zone fibrosis (GZF), assessed using cardiovascular magnetic resonance, are better than LVEF in predicting ventricular arrhythmias in patients with non-ischemic cardiomyopathy (NICM). Methods and results Patients with NICM in a derivation cohort (n=866) and a validation cohort (n=848) underwent quantification of TF and GZF. The primary composite endpoint was sudden cardiac death (SCD) or VAs (ventricular fibrillation or sustained ventricular tachycardia). The primary endpoint was met by 52/866 (6.0%) patients in the derivation cohort (follow-up of 7.5 years [interquartile range, IQR] 5.2-9.3). In competing risk analyses, MF on visual assessment (MFVA) predicted the primary endpoint (hazard ratio [HR] 5.83, 95% confidence intervals [CI] 3.15-10.8). Quantified MF measures permitted categorization into 3 risk groups: a TF >0 ≤ 10 g was associated with an intermediate risk (HR: 4.03 [95% CI 1.99-8.16]) and a TF > 10g with the highest risk (HR: 9.17 [95% CI 4.64-18.1]) compared to no MFVA (lowest risk) (Figure). Similar trends were observed in the validation cohort. Categorization into 3 risk groups was achievable using TF or GZF in combination or in isolation. In contrast, LVEF<35% was a poor predictor of the primary endpoint (validation cohort HR:1.99, 95% CI 0.99-0.41). Conclusions MFVA is a strong predictor of SCD and VAs in NICM. TF and GZF mass added incremental value to MFVA. In contrast, LVEF was not useful in arrhythmic risk stratification.

Background Myocardial fibrosis (MF) forms part of the arrhythmic substrate for ventricular arrhythmias (VAs). Objectives This study sought to determine whether total myocardial fibrosis (TF) and gray zone fibrosis (GZF), assessed using cardiovascular magnetic resonance, are better than left ventricular ejection fraction (LVEF) in predicting ventricular arrhythmias in patients with nonischemic cardiomyopathy (NICM). Methods Patients with NICM in a derivation cohort (n = 866) and a validation cohort (n = 848) underwent quantification of TF and GZF. The primary composite endpoint was sudden cardiac death or VAs (ventricular fibrillation or ventricular tachycardia). Results The primary endpoint was met by 52 of 866 (6.0%) patients in the derivation cohort (median follow-up: 7.5 years; Q1-Q3: 5.2-9.3 years). In competing-risks analyses, MF on visual assessment (MFVA) predicted the primary endpoint (HR: 5.83; 95% CI: 3.15-10.8). Quantified MF measures permitted categorization into 3 risk groups: a TF of >0 g and ≤10 g was associated with an intermediate risk (HR: 4.03; 95% CI: 1.99-8.16), and a TF of >10 g was associated with the highest risk (HR: 9.17; 95% CI: 4.64-18.1) compared to patients with no MFVA (lowest risk). Similar trends were observed in the validation cohort. Categorization into these 3 risk groups was achievable using TF or GZF in combination or in isolation. In contrast, LVEF of <35% was a poor predictor of the primary endpoint (validation cohort HR: 1.99; 95% CI: 0.99-4.01). Conclusions MFVA is a strong predictor of sudden cardiac death and VAs in NICM. TF and GZF mass added incremental value to MFVA. In contrast, LVEF was a poor discriminator of arrhythmic risk.