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Background: Long-term risk of post-discharge mortality associated with acute coronary syndrome remains a concern. The development of a model to reliably estimate two-year mortality risk from hospital discharge post-acute coronary syndrome will help guide treatment strategies.Methods: EPICOR (long-tErm follow uP of antithrombotic management patterns In acute CORonary syndrome patients, NCT01171404) and EPICOR Asia (EPICOR Asia, NCT01361386) are prospective observational studies of 23,489 patients hospitalized for an acute coronary syndrome event, who survived to discharge and were then followed up for two years. Patients were enrolled from 28 countries across Europe, Latin America and Asia. Risk scoring for two-year all-cause mortality risk was developed using identified predictive variables and forward stepwise Cox regression. Goodness-of-fit and discriminatory power was estimated.Results: Within two years of discharge 5.5% of patients died. We identified 17 independent mortality predictors: age, low ejection fraction, no coronary revascularization/thrombolysis, elevated serum creatinine, poor EQ-5D score, low haemoglobin, previous cardiac or chronic obstructive pulmonary disease, elevated blood glucose, on diuretics or an aldosterone inhibitor at discharge, male sex, low educational level, in-hospital cardiac complications, low body mass index, ST-segment elevation myocardial infarction diagnosis, and Killip class. Geographic variation in mortality risk was seen following adjustment for other predictive variables. The developed risk-scoring system provided excellent discrimination (c-statistic=0.80, 95% confidence interval=0.79–0.82) with a steep gradient in two-year mortality risk: >25% (top decile) vs. ~1% (bottom quintile). A simplified risk model with 11 predictors gave only slightly weaker discrimination (c-statistic=0.79, 95% confidence interval =0.78–0.81).Conclusions: This risk score for two-year post-discharge mortality in acute coronary syndrome patients (www.acsrisk.org) can facilitate identification of high-risk patients and help guide tailored secondary prevention measures.

Background: Atrial fibrillation (AF) is associated with increased morbidity in acute coronary syndrome patients, but impact on outcomes beyond 1 year is unclear.Methods: This was a post-hoc analysis from the long-tErm follow-uP of antithrombotic management patterns In acute CORonary syndrome patients (EPICOR) registry (NCT01171404), a prospective, observational study conducted in Europe and Latin America, which enrolled acute coronary syndrome survivors at discharge. Antithrombotic management patterns, mortality, a composite endpoint of death/new non-fatal myocardial infarction/stroke and bleeding events were assessed after 2 years of follow-up in patients with or without AF.Results: Of 10,568 patients enrolled, 397 (4.7%) had prior AF and 382 (3.6%) new-onset AF during index hospitalisation. Fewer patients with AF underwent percutaneous coronary intervention (52.1% vs. 66.6%; P<0.0001). At discharge, fewer AF patients received dual antiplatelet therapy (71.6% vs. 89.5%; P<0.0001); oral anticoagulant use was higher in AF patients but was still infrequent (35.0% vs. 2.5%; P<0.0001). Use of dual antiplatelet therapy and oral anticoagulants declined over follow-up with over 50% of all AF/no AF patients remaining on dual antiplatelet therapy (55.6% vs. 60.6%), and 23.3% (new-onset AF) to 42.1% (prior AF) on oral anticoagulants at 2 years. At 2 years, mortality, composite endpoint and bleeding rates were higher in AF patients (all P<0.0001) compared to patients without AF. On multivariable analysis, the risk of mortality or the composite endpoint was significant for prior AF (P=0.003, P=0.001) but not new-onset AF (P=0.88, P=0.92).Conclusions: Acute coronary syndrome patients with AF represent a high-risk group with increased event rates during long-term follow-up. Prior AF is an independent predictor of mortality and/or ischaemic events at 2 years. Use of anticoagulants in AF after acute coronary syndrome is still suboptimal.

Patients with dilated cardiomyopathy whose symptoms and cardiac function have recovered often ask whether their medications can be stopped. The safety of withdrawing treatment in this situation is unknown.

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Background: Standard of care (SOC) for second-line (2L) therapy (tx) of relapsed/refractory aggressive B-cell non-Hodgkin lymphomas (R/R aNHL) includes platinum-based chemotherapy (PCT) followed by autologous hematopoietic cell transplantation (aHCT) in responders. Outcomes are poor for patients (pts) with R/R aNHL who experience progression during or within 12 months (mo) of 1L tx. Tisagenlecleucel (tisa-cel) is an autologous chimeric antigen receptor (CAR) T-cell tx targeting CD19 approved for pts with large B-cell lymphoma (LBCL; US) and diffuse LBCL (non-US) after ≥2 lines of tx. BELINDA (NCT03570892) is a Phase III, randomized, global (18 countries) study of tisa-cel vs SOC as 2L tx for R/R aNHL.

Introduction:Atrial fibrillation (AF) in hypertrophic cardiomyopathy (HCM) is an important cause of premature morbidity and mortality. It often heralds significant symptomatic deterioration, heart failure and thromboembolic disease. Predictors of AF remain incompletely characterised, in particular the role of myocardial fibrosis. We used cardiovascular magnetic resonance (CMR) to assess predictors of AF in HCM.Methods:Consecutive patients with HCM referred for CMR assessment were prospectively enrolled between 2003 and 2013. CMR examination including measurement of left ventricular volumes, percentage of late gadolinium enhancement in the left ventricle (%LGE) and left atrial volume index (LAVi) were performed. Detailed medical records were obtained every 6 months from primary and secondary care and assessed for evidence of new AF.Results:Overall, 377 patients were recruited. The mean age was 61.8 ?13.6 years. Eighteen patients (4.8%) with baseline AF were excluded from further analysis. Sixty-two (16.4%) patients developed new-onset AF during a median follow up of 4.5 years (IQR 2.9 - 6.0). Multivariable analysis revealed %LGE, LAVi, age at diagnosis of HCM, history of NSVT and diabetes to be independent predictors of AF. LGE had a hazard ratio (HR) of 1.26 per 10% (CI: 1.04-1.53; p=0.02) and LAVi had a HR of 1.35 per 10mL/m2 (1.21-1.51; p<0.001). Estimated five-year event rates were six-fold greater (44.3% vs. 7.8%) in patients with both extensive %LGE (40%) and severely dilated LAVi (80ml/m2) compared to minimal %LGE (5%) and LAVi of 40ml/m2. We constructed a risk prediction score for future AF based on the multivariable model with a Harrell?s C-statistic of 0.733.Conclusions:Degree of ventricular replacement fibrosis and LA volume independently predict development of AF in HCM. This may suggest a mechanistic relationship between fibrosis and future AF in HCM. CMR has incremental benefit to echocardiography for risk stratification for AF and may be used as part of a prediction score for future AF. Patients at high risk of future AF may benefit from more intensive follow-up and a low threshold for oral anticoagulation.

Introduction:Traditional approaches to classification of dilated cardiomyopathy (DCM) mask disease heterogeneity for aetiology and progression.Hypothesis:The application of machine learning tools can maximally utilise multi-omics phenotyping in DCM to gain novel insights into disease pathobiology and prognostication.Methods:We applied semi-supervised Dirichlet Process Bayesian Clustering to a multi dimensional feature set of clinical, genetic, cardiovascular magnetic resonance and circulating proteomic markers (276 proteins) to define a set of ?phenotypic? subclasses of DCM. Patients were followed for the composite endpoint of cardiovascular death, major heart failure and major arrhythmic events. We assessed the additive value of patient clusters to established DCM survival models and identified biomarkers informative for outcome.Results:In index and validation cohorts of, respectively, 426 and 239 patients with DCM, we identified three novel phenotypic clusters informative for survival (Figure 1) and defined a novel subtype of DCM characterised by a greater number of co-morbidities, increased age, and increased myocardial fibrosis (Table 1). We also identified interleukin-4 receptor (IL4R) as a novel prognostic biomarker in DCM (primary cohort adjusted hazard ratio for primary endpoint 3.24, 95% CI 1.70 to 6.2, p=0.0004; validation cohort HR 1.94, 95% CI 1.34 to 2.8, p <0.0001).Conclusion:Application of machine learning tools to deep phenotyping can improve understanding of DCM pathobiology and identify novel prognostic markers.

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BackgroundThe DANISH trial emphasised that the selection of patients with dilated cardiomyopathy (DCM) for implantable cardioverter defibrillators (ICD) needs to be improved. Registries demonstrate that the major burden of sudden cardiac death (SCD) occurs in those with a left ventricular ejection fraction (LVEF) >35%. Those at high-risk of SCD with milder reductions in LVEF may gain greater quality-adjusted life years from successful ICD therapy compared to those with more severe reductions, due to a lower risk of death from competing non-sudden causes. Variables that identify patients with milder reductions in LVEF at high-risk of SCD are required.MethodsWe prospectively investigated the utility of mid-wall late gadolinium enhancement (LGE) cardiovascular magnetic resonance (CMR) to predict SCD and aborted SCD in consecutive patients with DCM and LVEF >40% seen in our cardiomyopathy service or referred for CMR between 2000 and 2011. Those with potential pre-existing indications for ICD implantation were excluded. The presence of LGE was determined by a specialist blinded to clinical data. A panel blinded to CMR data adjudicated end-point occurrences.ResultsOf 399 patients (145 women, median age 50 years, median LVEF 50%) followed for a median of 4.6 years, 18 of 101 (17.8%) with LGE reached the pre-specified end-point, compared to 7 of 298 (2.3%) without (HR 9.2; 95% CI 3.9–21.8; p<0.0001) (Figure 1). Nine patients (8.9%) with LGE compared to 6 (2.0%) without (HR 4.9; 95% CI 1.8–13.5; p=0.002) died suddenly, whilst 10 patients (9.9%) with LGE compared to 1 (0.3%) without (HR 34.8; 95% CI 4.6–266.6; p<0.001) had aborted SCD. Following adjustment based on propensity score, LGE predicted the composite end-point (HR 8.0; 95% CI 3.3–19.5; p<0.0001), SCD (HR 4.6; 95% CI 1.6–13.1; p=0.005) and aborted SCD (HR 32.9; 95% CI 4.3–249.9; p<0.001). Estimated hazard ratios for the primary end-point for patients with a LGE extent of 0%–2.5%, 2.5%–5% and >5% compared to those without LGE were 10.6 (95%CI 3.9–29.4), 4.9 (95% CI 1.3–18.9) and 11.8 (95% CI 4.3–32.3).ConclusionMid-wall LGE identifies patients with DCM and a LVEF >40% with an 8-fold increased risk of SCD and aborted SCD, who may benefit from ICD implantation.AcknowledgementsBPH is supported by a British Heart Foundation Clinical Research Training Fellowship. The study has also been supported by the Alexander Jansons Foundation and CORDA.