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Background The ACURATE neo™ is a novel, second-generation self-expanding supra-annular transcatheter heart valve (THV). The objective of this multi-centre registry is to assess the safety, clinical utility, and impact of 'learning-curve-experience' (LCE) on transcatheter aortic valve replacement outcomes in the United Kingdom (UK) and Ireland. Methods We prospectively collected data from seven ACURATE neo™ THV implanting centres (n = 484) between February 2016 and November 2020. We compared mortality rates and outcomes in the LCE group (n = 120) compared to next successive 120 cases. Results The mean age of the cohort was 81.9(SD: 6.1) years and the majority were in the moderate risk category (EuroSCORE-II):3.3(SD: 3). The 97.5% of cases were performed under local anesthetic. The valve was successfully deployed in 98.8% of cases. The survival rate at 30 days was 97.9%. The incidence of stroke was 2.5%. Life threatening bleeding occurred in 0.6% of cases and vascular access complications occurred in 21 (4.3%) patients. Implantation-related conduction abnormalities occurred in 8.3% but only 5.6% required a PPM. The successful valve deployment occurred in 96% of the patients in the LCE group compared to 100% in the other group (p = 0.04; OR-2[CI 1.7-2.3]). The mortality rates at 30 days (1.7% vs. 1.7%) and 1 year (1.9% vs. 2.7%) were comparable between the two groups. Conclusions This study represents the largest published UK and Ireland real-world experience of the ACURATE neo™ valve. The procedural success rates and safety outcomes were excellent and endorse its utility in clinical practice. The LCE appears to have an impact on the successful valve deployment but without translating into short-term or long-term outcomes.

A 62-year-old man presented at the height of the first wave of the coronavirus disease 2019 (COVID-19) pandemic with hypoxia, multi-organ failure and haemodynamic instability. The electrocardiogram and echocardiogram were indicative of inferolateral ST segment elevation myocardial infarction. His hypoxia was initially thought to be driven by acute pulmonary oedema due to cardiac failure, but this was out-of-proportion to his left-ventricular function. This aroused suspicion of COVID-19 which he subsequently tested positive for. He was not deemed to be candidate for primary percutaneous intervention, intubation or mechanical ventilation; a difficult decision to make in a previously healthy, young patient. Clinical decisions were complicated by late presentation and hospital pressures related to the pandemic. Similar clinical scenarios are likely as we move into the next stages of the pandemic. Establishing clinical frameworks to help clinicians make these decisions, and identifying barriers to healthcare attendance, may be priorities for policy-makers.

Background Chronic total occlusions (CTO) are a frequent angiographic finding. Viability of CTO-subtended myocardium is dependent on the presence of an adequate collateral circulation. At rest, collateral supply may be sufficient to avert ischaemia and maintain normal systolic function. However, it remains unclear whether CTO-subtended myocardium may be considered truly normal, or whether subtle functional abnormalities may be present at rest. Purpose To determine whether, in the absence of infarction and hibernation, CTO-subtended myocardium remains functionally normal or whether abnormalities of strain and/or mechanical dispersion may be present at rest. Methods In a retrospective, single centre, observational study, we studied patients with ≥1 angiographically-diagnosed CTO referred for clinical stress perfusion cardiovascular magnetic resonance (CMR), and compared healthy volunteers (HVs) with a normal stress CMR scan. CMR imaging comprised functional and scar assessment with qualitative [visual] evaluation of infarction and segmental wall motion. Patients with infarction and/or wall motion score index (WMSI) ≥1 were excluded from further analysis. In remaining CTO subjects and HVs, segmental peak systolic longitudinal strain and circumferential strain were analysed (in 3 long-axis planes and 3 short-axis planes, respectively) and mechanical dispersion for both orientations was computed. Image analysis was performed using Medis (QStrain) software blinded to all clinical information. Results From a total of 389 patients with ≥1 angiographically-diagnosed CTO, 68 had normal WMSI and no infarction (63.0±11.7 years, 79.4% male, LVEF 62.6±4.5%). Fifty HVs (61.1±7.0 years, 74.0% males, LVEF 61.1±5.3%) were also studied. The majority of CTO patients had concomitant coronary artery disease in at least one non-CTO vessel (n=37, 54.4%). GLS was lower in CTO patients than HVs (−21.8%±1.5% versus −24.0±1.1%; p Conclusion Subclinical changes in left ventricular dynamics are present at rest in CTO patients with fully viable myocardium and no evidence of resting regional wall abnormality. Further study is warranted to evaluate the potential association between mechanical dispersion and arrhythmic events in CTO. Funding Acknowledgement Type of funding sources: Other. Main funding source(s): NIHR Clinician Scientist Award (CS-2018-18-ST2-007 to J.R.A.) and Research Professorship award (RP-2017-08-ST2-007 to G.P.M.). Figure 1. Strain analysis. CTO vs HVFigure 2. Mechanical dispersion. CTO vs HV

A 73-year-old male was brought into hospital with chest pain and inferior ST elevation on ECG. The patient immediately proceeded to the catheter lab for primary percutaneous coronary intervention. Angiography did not identify any culprit lesions to account for the patient’s electrocardiographic changes and ongoing symptoms of chest pain. Bedside echocardiography revealed critical aortic stenosis. Intra-aortic balloon pump (IABP) was inserted, resulting in resolution of chest pain and ST-segment changes. The patient underwent successful aortic valve (AV) replacement without the need for coronary intervention. This is a rare presentation of critical aortic stenosis (AS) presenting as ST-segment elevation myocardial infarction (STEMI). Learning points: Aortic stenosis (AS) affects 2–9% of population above 65 years old and increases with age. AS induces ischaemia via abnormal cardiac coronary coupling. Focused clinical examination in patients with ST-segment elevation myocardial infarction (STEMI) is vital prior to cardiac catheterisation. Detection of murmurs should be followed on by an echocardiography examination. Other differentials of STEMI include acute aortopathy, endocarditis with embolus, myopericarditis and intracranial haemorrhage.

Objective Acute heart failure (AHF) is associated with high mortality and morbidity. Trimethylamine N -oxide (TMAO), a gut-derived metabolite, has reported association with mortality risk in chronic HF but this association in AHF is still unknown. The present study investigated TMAO in patients admitted to hospital with AHF, and association of circulating levels with prognosis. Methods In total, 972 plasma samples were analysed for TMAO concentration by liquid chromatography-mass spectrometry. Associations with in-hospital mortality (72 events), all-cause mortality (death, 268 events) and a composite of death or rehospitalisation due to HF (death/HF, 384 events) at 1 year were examined. Results TMAO improved risk stratification for in-hospital mortality in combination with current clinical scorings (OR≥1.13, p≤0.014). TMAO tertile analyses reported a graded risk in adverse outcome within 1 year (OR≥1.61, p≤0.004) and improved outcome prediction when stratified as none, one or both biomarker(s) elevated in combination with N-terminal pro B-type natriuretic peptide (NT-proBNP) (OR≥2.15, p≤0.007). TMAO was independently predictive for death and death/HF when corrected for cardiac risk factors (HR≥1.16, p≤0.037); however, this ability was weakened when indices of renal function were included, possibly due to multicollinearity. Conclusions TMAO contributed additional information on patient stratification for in-hospital mortality of AHF admissions using available clinical scores that include renal indices. Furthermore, elevated levels were associated with poor prognosis at 1 year and combination of TMAO and NT-proBNP provided additional prognostic information. TMAO was a univariate predictor of death and death/HF, and remained an independent predictor until adjusted for renal confounders.

Aims We sought to compare the prognostic utility of growth hormone (GH) with NT-proBNP) and the ADHERE score in a large cohort of acute heart failure (HF) patients, subcategorized into HF with reduced EF

A 25-year-old male with a background of ulcerative colitis presented with a two-week history of central chest pain. His ECG on presentation showed global T wave inversion with a peak troponin I of 165 ng/mL. Clinical diagnosis of myopericarditis/myocarditis was made. Echocardiography and cardiac magnetic resonance (MR) confirmed the diagnosis. On detailed assessment of his medication history, mesalazine was suspected as an etiological factor, with discontinuation resulting in an improvement in symptoms, inflammatory markers and cardiac enzymes. This is a unique case of mesalazine-induced myopericarditis on a background of inflammatory bowel disease. Learning points: Myopericarditis can be due to infectious and non-infectious causes. Myopericarditis may be related to systemic diseases such as inflammatory bowel disease (IBD) or as a consequence of its treatment. Cardiac magnetic resonance has proven to be a valuable technique for assessing myocardial injury and inflammation in myocarditis. Importance of taking a thorough medical history to distinguish the type of chest pain in order to make a correct diagnosis.

76-year-old female presented following an episode of collapse. She was hypotensive with the paramedics and remained refractory despite fluid resuscitation. Her initial baseline tests revealed an elevated troponin; she subsequently underwent a coronary angiogram that showed mild coronary artery disease. Left ventriculogram was performed, which showed abnormal mid-wall ballooning and severely impaired systolic function, characteristic of Takotsubo syndrome. Echocardiogram confirmed the presence of diagnosis and presence of left ventricular outflow tract obstruction with high gradient. She was initiated on medical heart failure therapy and improved. Follow-up investigations after 2 months showed complete resolution of systolic dysfunction and symptoms. Learning points: Takotsubo syndrome can present similarly to ACS. Early use of echocardiography in the acute setting can provide vital information. Takotsubo syndrome can result in hemodynamic instability requiring urgent interventions. Other investigative modalities can be used in conjunction with echocardiography to confirm the diagnosis of Takotsubo syndrome. Prognosis is generally good in patients with Takotsubo syndrome.

Endothelin-1 (ET-1) is a short chained peptide primarily of endothelial origin. Concentrations of this peptide are increased in subjects with hypertension, primary pulmonary hypertension and myocardial infarction, however its short half-life makes quantification difficult. The C-terminal of proET-1 (CTproET-1) is stoichiometrically secreted with its bioactive peptide and would be a valid method of measuring the active peptide as it has a stable half-life and is less resistant to proteolytic cleavage. The objective of this study was to understand the factors (clinical, echocardiographic and biochemical) that specifically influence plasma CTproET-1 in healthy subjects. 518 healthy volunteers were recruited from a screening study. Plasma CTproET-1 concentrations were quantified using a novel immunoluminometric sandwich assay. In multivariate analyses, age (P

Background: MRproADM and MRproANP can be used as diagnostic and prognostic markers in heart failure.Aim: The objective was to identify confounding factors for the interpretation of plasma MRproADM and MRproANP concentrations.Methods: A total of 518 healthy volunteers with a mean age of 60.84 ± 7.41 years were analyzed. We evaluated the influence of demographic factors, renal function and echocardiographic indices on the candidate peptides.Results: Multivariate analysis revealed that age (P

The present study sought to identify confounding factors for the interpretation of copeptin levels in healthy individuals. The natriuretic peptides are recognized as diagnostic and prognostic tools in HF (heart failure). Interpretation of BNP (brain natriuretic peptide) and NTproBNP (N-terminal pro-BNP) levels is multifaceted as their secretion is influenced by many variables. A newly identified glycopeptide called copeptin is comparable with the natriuretic peptides in the diagnosis and prognosis of HF and as a prognostic biomarker after AMI (acute myocardial infarction). Copeptin, derived from the C-terminal portion of the precursor to AVP (arginine vasopressin), is secreted stoichiometrically with vasopressin, hence it can be used as a surrogate marker of the AVP system. In the present study, 706 healthy volunteers were recruited from a local HF screening study. Participants with a history of cardiovascular disease and those with echocardiographic abnormalities were excluded from the study. Copeptin and NTproBNP levels were assayed using in-house immunoluminometric assays. Median copeptin levels were significantly higher in the male volunteers compared with the females [median (range): 4.3 (0.4–44.3) compared with 3.2 (1.0–14.8) pmol/l; P

UII is elevated in patients with heart failure; however its role in acute myocardial infarction (AMI) is unknown. We sought to compare levels of UII in patients with AMI to controls. We also compared UII to N terminal pro B type natriuretic peptide (NT-BNP) to evaluate whether levels of UII can be used to predict the risk of adverse clinical outcome (ACO).129 patients were studied with serial blood measurements and echocardiogram during their index admission. Plasma concentration of median UII was significantly elevated in AMI compared to controls (median 1.40 vs. 0.42 fmol/ml p0.012). Over the median follow up of 102 days (range 0-189) there were 14 deaths and 14 readmissions with AMI or heart failure. Using a Cox proportional hazards model the only independent predictors of ACO were UII (OR 0.29, p=0.046) and NT-BNP (OR 4.78, p=0.012) between 73 and 96 h. The Kaplan-Meier survival curve revealed a significantly better clinical outcome in patients with UII above the median compared with UII below the median.UII levels are raised in AMI and is an independent predictor of ACO. Patients with a poor outcome mount a lower UII response suggesting a possible cardioprotective role for this peptide.

Context: Excess growth hormone (GH) is associated with early mortality.Objectives: We assessed the association of GH with prognosis after acute myocardial infarction (AMI), and the effects of secondary prevention therapies.Methods: GH was measured using a high-sensitivity assay in 953 AMI patients (687 males, mean age 66.1 ± 12.8 years).Results: During 2 years follow-up, there were 281 major adverse cardiac events (MACE). Patients with MACE had higher GH levels (median [range], 0.91 [0.04–26.28] μg/L) compared to event-free survivors (0.59 [0.02–21.6], p

Introduction CAD is a leading cause of mortality in the UK with South Asians at heightened risk, owing to their disproportionately high prevalence of diabetes and metabolic syndrome. Simplistic notion of lipoprotein was transporters of lipids has been challenged, with a growing appreciation of their functionality, due to their carriage of low abundant proteins which are concerned with redox, inflammation and coagulation. In this study we sought to compare the lipoproteins and their associated protein cargoes between South Asian and Caucasian patients with CAD to further understand the differential risk that exists. Methods South Asian males (n = 51, age mean ± SD 58 ± 8.6years) and Caucasian males (n = 49, age mean ± SD 64 ± 8.7years) with angiographic evidence of CAD were recruited, after fulfilling the inclusion criteria, into this single centre prospective cohort study. Blood was withdrawn from the consented patients. Lipoproteins and their associated proteins were isolated using a novel lipoaffinity resin. A bottom-up label-free unbiased lipoproteomic discovery workflow was utilised. Samples were analysed on a Waters G2S high definition ion mobility enabled mass spectrometer. Data analysis was executed using Progenesis Qi with a stringent FDR of 1%. Results As expected South Asians were younger and had a higher prevalence of diabetes. Renal function, lipid parameters, burden of CAD and cardiovascular medication prescription were equivalent between the two ethnicities. 272 proteins were identified in both groups, of which 28 demonstrated significant differential expression (P < 0.05). South Asians were found to have enrichment of proteins concerned with acute inflammation (alpha-1 acid glycoprotein), complement activation (ficolin-2), extracellular remodelling (thrombospondin-1), endothelial dysfunction (profilin-1) and pro-thrombosis (thrombin activatable fibrinolysis inhibitor [TAFI]/carboxypeptidase B2) relative to Caucasians. South Asians had depletion of tetranectin, concerned with fibrinolysis, compared to their Caucasian counterparts. Biomarker verification revealed that plasma levels of TAFI were significantly higher in South Asian patients compared to Caucasian patients with CAD, using a single site in-house immunoassay (P = 0.045). Conclusion CAD remodels the lipoproteins and their associated protein cargo with ethnic specific alterations, such that South Asian patients have a predominance of pro-inflammatory and pro-thrombotic proteins compared to Caucasian patients. Higher plasma levels of TAFI in the South Asian patients relative to the Caucasian patients, may contribute to a pro-thrombotic state and to their excess CAD risk.

Left ventricular hypertrophy (LVH) is predictive of cardiovascular disease. The vasodilator, natriuretic and diuretic actions of atrial natriuretic peptide (ANP) support a role in the pathophysiology of hypertension. Measuring the redundant precursor fragment mid-regional portion of pro-atrial natriuretic peptide (MRproANP) overcomes the technical difficulties of quantifying the bioactive ANP. This study sought to investigate the diagnostic and prognostic utility of MRproANP in a hypertensive Caucasian patient population. A total of 194 hypertensive patients (39 patients with LVH, 69±7.82 years of age, 74% female vs 155 patients without LVH, 68±6.51 years of age, 71% female) were derived from a screening study. Plasma MRproANP concentrations were quantified using immunoluminometric assays. Hypertensive patients with LVH had higher MRproANP concentrations than those without LVH (103.04 (50.58) vs 84.11 pmol l(-1) (44.82); P=0.014). Independent predictors of left ventricular mass index were LogMRproANP (P=0.022), male gender (P0.001), body mass index (P=0.001) and history of angina or myocardial infarction (P=0.009). The receiver operating curve for MRproANP for the detection of LVH was limited, yielding an area under the curve of only 0.628 (confidence interval 0.523-0.733; P=0.014). Therefore, the role of MRproANP may not lie in the diagnosis of LVH but in monitoring the response to therapy. A nonsignificant trend towards greater mortality in patients with above-median MRproANP levels compared with below-median levels (P=0.167) was observed. Larger studies are required to assess its prognostic utility further.

Left ventricular hypertrophy (LVH) is a risk factor for cardiovascular disease. Elevated natriuretic peptides in LVH have spurred interest that biomarkers may play a role in screening programs. Adrenomedullin (ADM) is a 52–amino acid peptide mediating vasorelaxation, natriuresis, and diuresis. The midregional portion of proADM (MRproADM) is secreted stoichiometrically with ADM; hence, it can be used as a surrogate marker of ADM. We compared the diagnostic performance of MRproADM for the detection of LVH with N-terminal pro–B-type natriuretic peptide (NTproBNP). Two hundred fifty-three hypertensive patients were derived from a local screening study. The MRproADM and NTproBNP levels were assayed using immunoluminometric assays. The MRproADM levels were significantly elevated in patients with LVH than those without (mean [SD]: 0.73 [0.25] vs 0.59 [0.18] nmol/L, P < .001). In multivariate analyses, male sex (P < .001) and log MRproADM (P = .003) retained significance for detecting LVH. Receiver operating characteristic curve for MRproADM yielded an area under the curve of 0.71; confidence interval, 0.62-0.81; P < .001, superior to NTproBNP. An optimal cutoff value for MRproADM as an indicator of LVH was 0.50 nmol/L, with a sensitivity, specificity, and negative predictive value of 90.5%, 36.5%, and 95.1%, respectively. The high negative predictive value of the MRproADM assay allows it to be used as a rule-out test for LVH when stratifying patients into high or low risk. Patients who test positive would necessitate echocardiography, enabling better resource allocation.

Background The understanding of diastolic heart failure (DHF) has developed in recent years, a condition that was often misdiagnosed for systolic heart failure (SHF). Although there are constant advances in diagnostic technologies, treatment and diagnosis for DHF still remain a challenge prompting a need for biomarker discovery within human plasma. Prospecting for new protein biomarkers can be hindered by the presence of high abundant proteins (HAPs), masking the appearance of potentially diagnostic low abundance proteins (LAPs) due to their dominance in the sample matrix. A novel method, termed Mixed Mode Matrix (M3), is described to reduce the complexity and improve the dynamic range of plasma proteomics to investigate biomarkers in DHF. A pilot study involving controls (n = 10) and disease (DHF n = 10, SHF n = 10) plasma was carried out. Method HAPs were depleted using MARS14 column, bound to M3, eluted into fractions using increasing concentrations of NaH2PO4 and purified by solid-phase-extraction. A BCA protein assay was used to determine protein concentration prior to digestion. Peptides were separated using high-resolution liquid-chromatography (nano-UPLC) and high-definition-MSE analysis. Results A method for LAPs enrichment was developed. Over 300 LAPs were identified with 1% false discovery rate and contained at least 2 identified peptides. In depleting and enriching plasma with M3, we are able to expand the dynamic range of plasma thus enabling us to identify the LAPs. Conclusion M3 has the potential to improve efficiency and cost-effectiveness of LAPs enrichment, leading to plasma protein biomarker identification for diagnosis and treatment of a multitude of disease states.

Background Lipoproteins have an integral role in the pathogenesis of CAD. Quantitative proteomics is evolving to become an indispensable tool in the era of precision medicine. Using an unbiased lipoproteomic discovery workflow we sought to investigate the lipoproteomic differences between stable CAD patients and controls subjects and to reveal novel pathways/mechanisms that underpin this common disease. Methods Male patients with stable CAD (n = 49, mean ± SD; age 64 yrs ± 8.69) and without CAD (n = 17; mean age 74 yrs ± 6.21) were recruited into this single centre prospective cohort study. Plasma was co-incubated with a lipophilic affinity resin. Isolated lipoproteins were reduced, alkylated, digested and analysed using label-free high definition ion mobility enabled mass spectrometry. Raw data was analysed using Progenesis QI software with a stringent false discovery rate of 1%. Results 202 proteins showed significant differential expression between the CAD patients and the control subjects (P Conclusion Patients with CAD have a distinct pathognomonic lipoproteomic cargo. The measurement of certain lipoprotein associated proteins may assist in the early identification of such patients before symptom onset.

The benefit of statins in the prevention of cardiovascular disease is well founded, derived from their lipid lowering and pleiotropic effects. The concept of lipoproteins as lipid transporters has evolved to encompass functions in coagulation, inflammation, and redox reactions due to their unique protein cargo. The aim of this study was to determine the effect of statin therapy on lipoproteins and their protein cargo by use of an unbiased bottom-up proteomics approach in people with hypercholesterolaemia.11 people fulfilling the inclusion criteria were recruited into this UK-based single centre prospective observational study. They were started on statins for primary prevention. Blood was withdrawn at baseline and after a minimum of 2 months of statin therapy. Plasma was co-incubated with a lipoaffinity resin. Isolated proteins were digested and analysed with label-free two-dimensional liquid chromatography coupled to electrospray high-definition ion mobility tandem mass spectrometry.218 proteins were identified with Progenesis QI software, with 33 proteins demonstrating significant differential expression between the pre-statin and the on-statin samples (each p0·05). 17 proteins were upregulated by statin therapy, including proteins concerned with cytoskeletal organisation (vinculin p0·0001, tropomyosin α4 p=0·0108), antioxidative (peroxiredoxin 2 p=0·0092), and anti-inflammatory effects (transgelin-2 p=0·0071). Apolipoprotein B100 was downregulated by statin therapy, consistent with it mechanism of action (p=0·0006). Statin therapy downregulated novel proteins concerned with the modulation of pancreatic β-cell function (adipsin p=0·0056) and haemopoietic precursor proliferation (stem cell growth factor p0·0001).Our findings show that statins remodel the cytoskeletal architecture and mediate various anti-inflammatory, antioxidant, and antiproliferative effects that might limit endothelial dysfunction. The downregulation of adipsin, a novel adipokine that stimulates insulin secretion, could explain the controversial link between statin use and the development of diabetes. This study extends our understanding of the beneficial and harmful pleiotropic effects of statin therapy.British Heart Foundation.