Abstract Introduction Sterile inflammation post myocardial infarction (MI) is essential to activation reparative mechanisms. However, excessive inflammation contributes to detrimental recovery and adverse outcomes(1). Several studies have reported an association between elevated leucocyte subpopulations and neutrophil-lymphocyte ratio (NLR) with poor prognosis after MI(2). In healthy volunteers, it is known that black individuals have a lower diurnal neutrophil, basophil, and monocyte count and the term ‘benign ethnic neutropenia’ has been used(3). However, the effect of ethnicity on leucocyte counts after MI is not known. Purpose We aimed to assess the interaction between ethnicity and leucocyte subpopulations and NLR. Understanding post-MI inflammation and its interaction with ethnicity is essential in providing personalised patient management and prognostication. Methods We conducted a single centre retrospective observational study of consecutive patients presenting with ST-segment elevation MI (STEMI) between 2016 and 2022. Patients were divided into white and other ethnic groups combined (‘ethnic minorities’) based on self-reported ethnicity. Leucocyte subpopulations, neutrophil and monocyte lymphocyte ratios (NLR and MLR, respectively) at baseline and for 4 days post admission were compared. Baseline variables were analysed with Shapiro-Wilk testing and presented as median (IQR). Area under the curve (AUC) was used to analyse magnitude of change in longitudinal analysis with smoothed conditional means (LOESS) to display trends in the data. Univariate and multivariate linear regression analyses were used to investigate for an association between ethnicity and baseline clinical variables. Results We included 1933 STEMI patients, of whom 1477 (76%) were white and 456 (24%) were from ethnic minority groups. Baseline neutrophils (7.73 [5.9-10] vs 9.04 [6.7-11.9] x109/L), monocytes (0.52 [0.38-0.69] vs 0.6 [0.44-0.82] x109/L), basophils (0.03 [0.02-0.04] vs 0.04 [0.02-0.06] x109/L), NLR (4.47 [2.93-7.19] vs 5.61 [3.64-8.89]) and MLR (0.3 [0.21-0.43] vs 0.36 [0.26-0.53]) were significantly lower (all p<0.001) in ethnic minority vs white patients. There were no differences in peak troponin T or CRP. Longitudinal assessment of leucocyte subgroups and NLR showed that white patients had a significantly higher AUC and difference between minimum and maximum values (delta) for neutrophils, monocytes, basophils and NLR (Panel 1). After correction, we observed a negative association between being in the ethnic minority group and baseline NLR (p=0.005) and basophil count (p<0.001). Conclusions Despite baseline differences in leucocyte subgroups and NLR according to ethnicity, there is a distinct interaction among patients with STEMI suggesting an ethnicity-specific inflammatory profile. Blunting of the magnitude and duration of leucocyte response is novel, and future work will focus on the implications for prognosis and tailored therapy.

Type of funding sources: Foundation. Main funding source(s): British Heart foundation Haematopoietic stem cells can acquire mutations and produce mutant blood cells. When this occurs in the absence of overt blood disease, it is clonal haematopoiesis of indeterminate potential (CHIP). CHIP is a novel, independent risk factor for ischaemic heart disease and heart failure (HF)(1). However, the molecular mechanisms are poorly understood. Myocardial infarction (MI) is a leading cause of HF due to ventricular remodelling and scar formation(2). We postulate CHIP mutations result in aberrant inflammation that contributes to maladaptive ventricular remodelling following MI. We investigated clinical outcomes and immune cell biology in CHIP and non-CHIP patients (pts) with acute ST-segment elevation MI (STEMI). Identify and quantify mutations with variant allele frequency (VAF)≥1% in STEMI pts. Assess leukocyte mutational burden. Investigate transcription profiles and leukocyte function in CHIP and non-CHIP STEMI pts. 119 pts diagnosed with STEMI were prospectively recruited (REC19/SC/0362). We collected clinical data, including echocardiogram (echo) parameters and isolated plasma and peripheral blood mononucleated cells (PBMCs) from blood collected 48-96 hours post onset of chest pain. PBMCs were screened for mutations and analysed by flow cytometry. We assessed CHIP VAF with digital droplet PCR in flow-sorted monocytes (Mono), T and B-cells. We performed single-cell RNAseq (10x Genomics) on PBMCs. Luminex or ELISA kits were used to measure plasma proteins. 59/119 recruited pts had CHIP (VAF≥1%). CHIP pts were significantly older than non-CHIP pts. DNMT3A was the most commonly mutated gene (28%), followed by TET2 (17%) and ASXL1 (5.3%). 53 pts had impaired LV ejection fraction (LVEF) at admission and a follow-up Echo at median 4.6 months (2.5-8 IQR) post STEMI. They were classified as responder (R) n=24, Δ LVEF≥5% or non-responder (NR) n=29, ΔLVEF<5%. Pts with DNMT3A CHIP were 12 times more likely to be NR (p=0.02). Baseline LVEF was similar in CHIP and non-CHIP pts, but ΔLVEF was significantly reduced in DNMT3A vs non-CHIP pts (p<0.01). DNMT3A mutations were highest in Mono (mean VAF 6.3%), present in B cells (3%) but rare in T cells (1.7%). Within the Mono population, DNMT3A mutant pts had significantly higher proportions of classical Mono compared to non-CHIP (p=0.02). Using scRNAseq, we computed Mono trajectories and differential gene expression. Compared to non-CHIP, DNMT3A-mutant samples upregulated receptor for advanced glycation end-products (RAGE) and toll-like receptor signaling gene signatures. Despite this, we did not observe raised leukocyte count or detect increased levels of inflammatory cytokines in DNMT3A-mutant pts plasma samples. DNMT3A CHIP is associated with poor LVEF recovery post-STEMI due to a dysregulated inflammatory response to acute myocardial injury. Furthermore, our data suggests that this may occur via different mechanisms than non-CHIP NR.

Abstract Introduction The use of anthracycline chemotherapy is complicated by the risk of developing cancer therapy-related cardiac dysfunction (CTRCD). The Heart Failure Association (HFA) and International Cardio-Oncology Society (ICOS) have jointly published a novel cardiovascular risk stratification tool for patients receiving anthracycline chemotherapy which categorises patients according to their risk of CTRCD (1). The risk tool has not yet been validated for use in the United Kingdom. Purpose In this study, we test the ability of the HFA-ICOS risk stratification tool to predict CTRCD for patients receiving anthracycline chemotherapy. Methods A retrospective study of patients ≥18 years who received anthracycline chemotherapy between January 2019 to January 2023 at two cardio-oncology centres in the United Kingdom. Patients were eligible if they had ≥1 follow up echocardiogram after the end of anthracycline treatment. Patients receiving HER-2 targeted therapies were excluded. Patients were classified into low/medium/high/very-high risk categories using the HFA/ICOS tool. The prevalence of CTRCD was assessed during the follow up period; a minimum of 6 months after the end of chemotherapy. Results 288 patients met eligibility criteria for the study. 59 patients (20%) were treated for leukaemia, 104 (36%) lymphoma, 63 (22%) sarcoma and 49 (17%) breast cancer. The mean age was 49±18yrs, with 56% females. The mean cumulative dose of doxorubicin (or equivalent) was 235±104mg/m2. Using the HFA/ICOS tool, 50% of patients were deemed low risk, 31% medium risk, 16% high risk and 3% very high risk at baseline. Using guideline recommended CTRCD definitions, there was an overall incidence of 9% of symptomatic CTRCD and 22% of asymptomatic CTRCD (Table 1). The incidence of symptomatic CTRCD significantly increased as the baseline risk of CTRCD increased. 20% of patients deemed high or very-high risk at baseline subsequently developed symptomatic CTRCD (Fig 1). Furthermore, patients at high or very-high risk were 4.4 times more likely to develop symptomatic CTRCD than patients who were low risk (OR 4.4, 95% CI 1.7-11.6, p=0.003). There was no association with baseline risk and the development of asymptomatic CTRCD. The incidence of mild asymptomatic CTRCD may be underestimated due to the lack of routine surveillance with cardiac biomarkers and left ventricular global longitudinal strain (LV GLS) imaging for asymptomatic disease during the study period. Conclusion The novel HFA/ICOS risk stratification tool is useful in predicting patients who will develop symptomatic CTRCD in a contemporary UK setting.

Abstract Introduction Anthracyclines are a highly effective class of chemotherapy used to treat a wide variety of malignancies. Their use is complicated by the development of cancer therapy-related cardiac dysfunction (CT-RCD), defined broadly as the development of left ventricular systolic dysfunction following cancer treatment. Troponin, a well-established marker of myocardial necrosis and early myocardial injury following anthracycline chemotherapy, may predict the subsequent development of CT-RCD. It is not known, however, at what timepoint troponin should be measured, or if there is a clinically relevant threshold that best predicts the development of CT-RCD. Purpose 1. To investigate if high sensitivity troponin T (hsTnT) accurately predicts the development of anthracycline CT-RCD 2. To establish the best timepoint at which hsTnT should be measured to predict CT-RCD 3. To establish the most clinically relevant hsTnT concentration to predict CT-RCD Methods In 2020 we introduced a clinical pathway for outpatients receiving anthracycline chemotherapy at our Institution. As part of this pathway, hsTnT concentrations are measured at baseline (pre-chemotherapy) and prior to each anthracycline cycle. In this study, we performed a prospective audit of outpatients receiving anthracycline chemotherapy for the treatment of breast or haematological malignancies. Troponin concentrations prior to each chemotherapy cycle were assessed and ROC curve analyses were performed to determine the most accurate timepoint and threshold to predict CT-RCD. CT-RCD was defined as a drop in the left ventricular ejection fraction (LVEF) of >10% from baseline to a value of <50%. Results 118 outpatients were treated with anthracycline chemotherapy between August 2020 and May 2022. 64 patients (54%) were treated for breast cancer and 54 (46%) for haematological malignancies. The mean age was 54±15yrs, with 71% females. At baseline, 27 (23%) of patients had a diagnosis of hypertension, 16 (14%) diabetes, 28 (24%) smoking history, 10 (8%) chronic kidney disease and 31 (26%) obesity. The median cumulative dose was 360mg/m² for Epirubicin and 300mg/m² for Doxorubicin. The baseline mean LVEF was 60.5±4%. 97/118 (82%) of patients had a follow up echocardiogram. 11/97 (11%) of patients developed CT-RCD. Mean hsTnT concentrations rose incrementally as the cumulative dose of anthracycline increased (Fig 1). Baseline hsTnT concentration was the most accurate predictor of subsequent CT-RCD (AUC 0.75), with a 75% sensitivity and 80% specificity for predicting CT-RCD if the baseline hsTnT concentration was ≥10.5ng/L. In addition, the baseline mean hsTnT concentration was significantly higher in patients with CT-RCD vs. those with no CT-RCD, P=0.0008 (Fig 2). Conclusions High sensitivity troponin T concentrations appear to be clinically useful in predicting subsequent CT-RCD, with the most accurate point of measurement being at baseline, prior to chemotherapy commencing.

Abstract Background Acute myocarditis (AM) is an inflammatory disease of the myocardium that is associated with heterogenous clinical presentations, which may be non-specific. Furthermore, several cardiac diseases can mimic its clinical phenotype. Research in AM frequently utilises ICD-10 codes from hospital admissions for case identification. We retrospectively confirmed or refuted a diagnosis of AM according to ESC Position Statement criteria in patients with an ICD-10 code for AM. Methods We performed a single-centre retrospective analysis of all unique admissions with ICD-10 codes corresponding to myocarditis or myopericarditis in the first three coding positions at King's College Hospital, London, United Kingdom. The diagnosis was classified as “confirmed” if proven by cardiac magnetic resonance imaging (CMR) or endomyocardial biopsy (EMB) or “suspected” in the absence of CMR or EMB if other ESC Position Statement criteria were met. To identify additional cases, we used an open-source retrieval system for unstructured clinical data (CogStack). We searched hospital and Intensive Care Unit (ICU) discharge summaries for inpatients discharged alive containing the keywords “myocarditis” or “myopericarditis”. We also searched for patients who died during the study period where the keywords “myocarditis” or “myopericarditis” were included on the death notification. Results We identified 308 unique admissions with an ICD-10 code for myocarditis or myopericarditis in this study, presenting between 2008 and 2020 (Figure 1). Overall, 26.0% of patients (n=80/308) could be excluded from a diagnosis of AM on review of the clinical summary. A total of 16.2% of patients (n=50/308) had insufficient evidence of AM, 1.9% (n=6/308) had not had coronary artery disease excluded as a culprit for the presentation, and 10.1% (n=31/308) had an alternative diagnosis. Only 45.8% (n=141/308) of all patients met criteria for suspected or confirmed AM. Of those, 86.5% (n=122/141) of cases were confirmed by CMR. Overall, 39.6% of patients with an ICD-10 code indicating AM had a confirmed diagnosis. An additional 46 suspected and 197 confirmed cases were identified using open-source retrieval from unstructured clinical data. Conclusion AM has heterogenous and sometimes non-specific clinical presentations, which may be compounded by limited access to CMR and EMB. We identified significant misclassification using ICD-10 codes. It is crucial to ensure that studies investigating AM include only patients meeting appropriate diagnostic criteria, thereby ensuring a high-quality evidence base in this disease. Funding Acknowledgement Type of funding sources: None.

Abstract Funding Acknowledgements Type of funding sources: None. Introduction Generic ICD programming, where shock-reduction programming is extrapolated from trials of one manufacturer to another, may reduce non-essential ICD therapies beyond that seen in randomised trials. The purpose of this retrospective cohort study was to evaluate the impact of a standardised programming protocol, based on generic programming, across manufacturers. We also evalutated the impact of combining different detection rates and detection times. Methods We included all new ICDs in a single centre (2009-2019). In 2013 a standardised programming protocol based on generic programming was introduced. Patients were classified into three groups: pre-guideline (PS), post-guideline and guideline compliant (GC) and post-guideline but not guideline compliant (NGC). The end-points were the first occurrence of any device therapy (ATP or shock), ICD shock, syncope and all-cause mortality. Survival analysis was used to evaluate outcomes. A ’’programming score’’ was composed based on detection rate and time. The relationship between this composite "programming score’’ and study end-points was evaluated in multivariable cox proportional hazards models Results 1003 patients were included (mean follow-up 1519 +/- 1005 days). In primary prevention patients freedom from ICD therapy (91.5% vs. 73.6%, p<0.001) or shock (94.7% vs 84.8%, p=0.02) were significantly higher in GC compared to PS patients, without significant increase in syncope or mortality. In secondary prevention patients freedom from any ICD therapy or any shock were non-significantly higher in GC compared to PS patients. Among primary prevention patients with the highest ’programming score’ (longest detection time and highest detection rates), there was a 82% reduction in risk of any ICD therapy (p<0.001) and a 70% reduction in risk of ICD shock (p<0.001) Conclusion A standardised programming protocol, incorporating generic programming, reduced the burden of ICD therapy without an increase in adverse outcomes.

Abstract Aims Chemotherapy‐induced dilated cardiomyopathy (CI‐DCM) is a well‐recognized phenotype of non‐ischemic dilated cardiomyopathy (DCM), characterized by poor outcomes. However, a detailed comparison between idiopathic DCM (iDCM) and CI‐DCM is still lacking. Methods and results All consecutive DCM patients enrolled in the Trieste Muscle Heart Disease Registry were analysed. CI‐DCM and iDCM were defined according to current recommendations. The primary study outcome measure was all‐mortality death and secondary outcomes were a) a composite of cardiovascular death/heart‐transplantation/ventricular‐assist‐device implantation, and b) major ventricular arrhythmias. The study included 551 patients (499 iDCM and 52 CI‐DCM). At enrolment, compared with iDCM, CI‐DCM patients were older (51 ± 14 years vs. 58 ± 3 years, respectively, P < 0.001) and had a higher left ventricular ejection fraction (32% ± 9 vs. 35% ± 10, respectively, P = 0.03). Over a median follow‐up of 90 months (IQR 54–140 months), CI‐DCM patients had a higher incidence of all‐cause mortality compared with iDCM (36.5% vs. 8.4% in CI‐DCM and iDCM respectively, P < 0.001), while the incidence of major ventricular arrhythmias was higher in the iDCM group compared with CI‐DCM (4% vs. 0%, in CI‐DCM and iDCM respectively, P = 0.03). The risk of the composite outcome was comparable between the two groups (P = 0.91). At Cox multivariable analysis, the diagnosis of CI‐DCM emerged as independently associated to primary outcome (HR 6.42, 95% C.I. 2.52–16.31, P < 0.001). Conclusions In a well‐selected DCM cohort, patients with a chemotherapy‐induced aetiology had a higher incidence of all‐cause mortality compared with iDCM. Conversely, the incidence of life‐threatening ventricular arrhythmic events was higher among patients with iDCM.

Abstract Background Neutrophil–lymphocyte ratio (NLR) is an easily obtained inflammatory biomarker. Recently it has emerged as baseline NLR is independently associated with incident cardiovascular (CV) events and all-cause mortality. However, its role in acute myocarditis (AM) has not been evaluated. Purpose The aim of the present study was to investigate the prognostic value of NLR in patients with AM. Methods All consecutive patients with a diagnosis of AM admitted to two tertiary referral cardiac centres (King's College Hospital, London, UK and Azienda Sanitaria Universitaria Giuliano-Isontina, Trieste, Italy) between October 2006 and June 2020 were included in the study. Diagnosis was confirmed by either cardiac magnetic resonance or endomyocardial biopsy. The outcome measure was all-cause mortality. Patients were divided into two groups according to NLR value defined in previous studies (i.e, 2.5). Results A total of 260 patients with AM were included in the study. Baseline characteristics were comparable in both groups. Approximately two thirds of patients were males (n=175, 67%) with a mean age of 45±16 years. Main clinical presentation was predominantly infarct-like (n=189, 73%), followed by heart failure (HF) (n=46, 18%) and arrhythmic (n=25, 10%). Patients admitted with a HF presentation were more prevalent in the group with elevated NLR, while no difference was found in the other clinical presentations. For all patients, ECG features were comparable between groups. However, patients with elevated NLR presented with slightly lower LVEF (54±11% vs 49±13% respectively, p=0.001). Higher NLR was associated with worse prognosis (Figure 1, p=0.02). Conclusions The NLR is a promising and accessible inflammatory biomarker. In patients with AM, elevated NLR is associated with worse prognosis. Further research is advocated to confirm these data in larger populations.

Abstract Funding Acknowledgements Type of funding sources: None. Background Limited data is available in the literature on Cardiac Magnetic Resonance (CMR) features of African/Afro-Caribbeans, in particular exploring differences between hypertensive heart disease (HHD) and hypertrophic cardiomyopathy (HCM). Purpose To describe the cardiac morphology and pattern of late gadolinium enhancement (LGE) in patients of African/Afro-Caribbean origin. Methods We retrospectively analysed African/Afro-Caribbean patients who underwent clinical CMR at a tertiary centre. Three groups were specifically investigated: HHD, HCM and combination of HHD and HCM or ambiguous (HHD&HCM). Results Overall, 166 consecutive patients (58% male, mean age 55 ± 14yo) were analysed. One-hundred fifty-four (93%) had history of arterial hypertension (HTN), including 17 with uncontrolled/malignant HTN. Overall, 28(17%) had normal scans, 70(42%) HHD, 15(9%) apical HCM, 10(6%) classical septal HCM, 19(11%) dilated cardiomyopathy, 6(4%) cardiac amyloidosis, 3(2%) ischemic heart disease, 4(2%) myocarditis, 2 sarcoidosis and 1 valvular disease. In 7(4%) the diagnosis was ambiguous between HHD and HCM and 1 uncertain. Forty-four (27%) had dual pathology, most frequently HHD, bystander myocardial infarction (MI) and embolic MI. LGE was detected in 95(57%), 26 with ischemic pattern, 13 diffuse mid-wall, 29 focal non-ischemic and 28 diffuse/multifocal non-ischemic. CMR features and correlations between subgroups are reported in the Table. Patients with HHD had significantly higher left ventricular (LV) end-diastolic (ED) volume indexed (Vi) and LV end-systolic (ES) Vi, but lower LV ejection fraction (EF) and LV maximum wall thickness (MWT) compared to HCM patients. HHD&HCM had higher LVEF and MWT compared to HHD and higher LVEDVi compared to HCM. LGE was more frequently seen in HCM and HHD&HCM as focal non-ischemic (6vs5vs10,p = 0.049) and diffuse multifocal(5vs6vs9,p = 0.009). A history of uncontrolled/malignant HTN was more frequent in HHD and HHD&HCM (11vs1vs5,p = 0.025) and was associated with diffuse LGE with lateral wall involvement (p < 0.0001) (Figure). Conclusions: CMR findings in African/Afro-Caribbeans may overlap between aetiologies. A specific pattern of diffuse non-ischaemic LGE involving the lateral wall appears though to be more often associated with severe uncontrolled HTN. Table HHD(n = 70) HCM(n = 19) HHD&HCM or ambiguous (n = 13) p LVEDVi, ml/m2 88 ± 33 62 ± 11 77 ± 6 0.003 LVESVi, ml/m2 36 ± 26 16 ± 10 26 ± 19 0.002 LVEF, % 62 ± 16 79 ± 6 74 ± 12 0.567 LVMWT, mm 13 ± 2 15 ± 4 14 ± 3 <0.0001 CMR features and correlations between subgroups Abstract Figure

Background Myositis is a systemic autoimmune condition causing skeletal muscle inflammation and fibrosis as well as extra skeletal involvement. Cardiac involvement is well described and has morbidity and mortality. It can be diffuse or focal which can make assessment using conventional imaging techniques more difficult. To date the incidence is poorly defined using conventional cardiac investigations. Purpose To investigate the reproducibility of a 12 segment ventricular myocardial model of T1 and T2 mapping in healthy volunteers and then to use this methodology in patients with myositis, comparing it to the current non invasive gold standard of troponin I level for cardiac involvement and then monitor how it changes with time and treatment. Methods 19 Healthy volunteers were scanned at 1.5T. T1 (using a MOLLI sequence) and T2 mapping were performed in basal and mid short axis. The images were analysed by blinded readers to assess the reproducibility of the 12 segment myocardial segmentation approach. Patients were recruited from the Rheumatology department which is a regional centre for myositis. Patients with cardiac symptoms or elevated troponin I were recruited. Recruits underwent CMR with tissue mapping and late gadolinium enhancement at the first visit with 2 subsequent non-contrast mapping studies followed by a final gadolinium enhanced CMR at 12 months. All patient scans were performed on the same 1.5T scanner and analysed by the same reader. In order to mitigate for bias a second reader, blinded to the clinical details including the troponin, repeated the analysis on 50% of studies. The T1 and T2 were calculated for 12 segments in each scan. Results Reproducibility of a 12 segment model for analysing tissue mapping sequences is excellent with a coefficient of variability of 1.4% for T1% and 2.6% for T2. Myositis patients with elevated troponin I had a significantly higher mean T1 and T2 than healthy volunteers (p<0.0001 both). Myositis patients with elevated troponin i have a significantly higher T1 and T2 than myositis patients with normal troponin I (p<0.01 both). Patients with myositis and a negative troponin I have a significantly higher T1 and T2 than healthy volunteers (T1 p<0.01, T2 p<0.05). There is a significant reduction in T1 and T2 values in patients with treatment over 8 months (p<0.05 both). Conclusions A twelve segment model for myocardial T1 and T2 assessment is highly reproducible which is important in this disease process as there can be either focal or diffuse myocardial involvement. T1 and T2 are strongly associated with troponin I positivity with both likely to be a reflection of active inflammation in this disease process and improve with immunesuppression therapy fairly quickly.

The vast majority of therapies for heart failure (HF) are based on randomised clinical trials of highly heterogenous groups of patients. Mortality and morbidity remain substantial even in patients who are optimally treated with such therapies. There is therefore significant interest in identifying biomarkers that might enable earlier or more refined diagnosis, staging, prognostication and personalisation of therapy. The only biomarker that is routinely employed in clinical practice is NT-proBNP but this is useful mainly in informing the likelihood of HF rather than guiding therapy.