<div><h4>Phenotyping of atrial fibrillation with cluster analysis and external validation.</h4><i>Saito Y, Omae Y, Nagashima K, Miyauchi K, ... Minamino T, Okumura Y</i><br /><b>Objectives</b><br />Atrial fibrillation (AF) is a heterogeneous condition. We performed a cluster analysis in a cohort of patients with AF and assessed the prognostic implication of the identified cluster phenotypes.<br /><b>Methods</b><br />We used two multicentre, prospective, observational registries of AF: the SAKURA AF registry (Real World Survey of Atrial Fibrillation Patients Treated with Warfarin and Non-vitamin K Antagonist Oral Anticoagulants) (n=3055, derivation cohort) and the RAFFINE registry (Registry of Japanese Patients with Atrial Fibrillation Focused on anticoagulant therapy in New Era) (n=3852, validation cohort). Cluster analysis was performed by the K-prototype method with 14 clinical variables. The endpoints were all-cause mortality and composite cardiovascular events.<br /><b>Results</b><br />The analysis subclassified derivation cohort patients into five clusters. Cluster 1 (n=414, 13.6%) was characterised by younger men with a low prevalence of comorbidities; cluster 2 (n=1003, 32.8%) by a high prevalence of hypertension; cluster 3 (n=517, 16.9%) by older patients without hypertension; cluster 4 (n=652, 21.3%) by the oldest patients, who were mainly female and with a high prevalence of heart failure history; and cluster 5 (n=469, 15.3%) by older patients with high prevalence of diabetes and ischaemic heart disease. During follow-up, the risk of all-cause mortality and composite cardiovascular events increased across clusters (log-rank p<0.001, p<0.001). Similar results were found in the external validation cohort.<br /><b>Conclusions</b><br />Machine learning-based cluster analysis identified five different phenotypes of AF with unique clinical characteristics and different clinical outcomes. The use of these phenotypes may help identify high-risk patients with AF.<br /><br />© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.<br /><br /><small>Heart: 01 Jun 2023; epub ahead of print</small></div>

<div><h4>Fixed dose combination therapies in primary cardiovascular disease prevention in different groups: an individual participant meta-analysis.</h4><i>Dagenais GR, Pais P, Gao P, Roshandel G, ... Joseph P, Yusuf S</i><br /><b>Objective</b><br />To evaluate the effects of fixed dose combination (FDC) medications on cardiovascular outcomes in different age groups in an individual participant meta-analysis of three primary prevention randomised trials.<br /><b>Methods</b><br />Participants at intermediate risk (17.7% mean 10-year Framingham Cardiovascular Risk Score), randomised to FDC of two or more antihypertensives and a statin with or without aspirin, or to their respective control, were followed up for 5 years. Age groups were <60, 60-65 and ≥65 years. The primary outcome was cardiovascular death, myocardial infarction, stroke or revascularisation. Cox proportional HRs and 95% CIs were computed within each age group.<br /><b>Results</b><br />The primary outcome risk was reduced by 37% (3.3% in FDC vs 5.2% in control (HR 0.63; 95% CI 0.54 to 0.74)) in the total population of 18 162 participants with larger benefits in older groups (HR 0.58; 95% CI 0.42 to 0.78, 60 to 65 years) and (HR 0.57; 95% CI 0.47 to 0.70, ≥65 years), as were their numbers needed to treat to avoid one primary outcome: 53 and 33, respectively. The primary outcome risk was reduced in the two oldest groups with FDC with aspirin (n=8951) by 54% and 54%, and without aspirin (n=12 061) by 34% and 38%. Dizziness, the most frequent FDC adverse effects, was higher in participants aged <65 years. Aspirin was not associated with significant bleeding excess.<br /><b>Conclusions</b><br />In participants with intermediate cardiovascular risk, FDCs produce larger cardiovascular benefits in older individuals, which appear greater with aspirin.<br /><b>Trial registration number</b><br />HOPE-3, NCT00468923; TIPS-3, NCT016464137; PolyIran, NCT01271985.<br /><br />© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.<br /><br /><small>Heart: 31 May 2023; epub ahead of print</small></div>

<div><h4>Evaluation of hospital readmission rates as a quality metric in adult cardiac surgery.</h4><i>Ebrahimian S, Bakhtiyar SS, Verma A, Williamson C, ... Sanaiha Y, Benharash P</i><br /><b>Objective</b><br />To assess the reliability of 30-day non-elective readmissions as a quality metric for adult cardiac surgery.<br /><b>Background</b><br />Unplanned readmissions is a quality metric for adult cardiac surgery. However, its reliability in benchmarking hospitals remains under-explored.<br /><b>Methods</b><br />Adults undergoing elective isolated coronary artery bypass grafting (CABG), surgical aortic valve replacement/repair (SAVR) or mitral valve replacement/repair (MVR) were tabulated from 2019 Nationwide Readmissions Database. Multi-level regressions were developed to model the likelihood of 30-day unplanned readmissions and major adverse events (MAE). Random intercepts were estimated, and associations between hospital-specific risk-adjusted rates of readmissions and were assessed using the Pearson correlation coefficient (r).<br /><b>Results</b><br />Of an estimated 86 024 patients meeting study criteria across 298 hospitals, 62.6% underwent CABG, 22.5% SAVR and 14.9% MVR. Unadjusted readmission rates following CABG, SAVR and MVR were 8.4%, 9.3% and 11.8%, respectively. Unadjusted MAE rates following CABG, SAVR and MVR were 35.1%, 32.3% and 37.0%, respectively. Following adjustment, interhospital differences accounted for 4.1% of explained variance in readmissions for CABG, 7.6% for SAVR and 10.0% for MVR. There was no association between readmission rates for CABG and SAVR (r=0.10, p=0.09) or SAVR and MVR (r=0.09, p=0.1). A weak association was noted between readmission rates for CABG and MVR (r=0.20, p<0.001). There was no significant association between readmission and MAE for CABG (r=0.06, p=0.2), SAVR (r=0.04, p=0.4) and MVR (r=-0.03, p=0.6).<br /><b>Conclusion</b><br />Our findings suggest that readmissions following adult cardiac surgery may not be an ideal quality measure as hospital factors do not appear to influence this outcome.<br /><br />© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.<br /><br /><small>Heart: 31 May 2023; epub ahead of print</small></div>

<div><h4>A narrative review of heart failure with preserved ejection fraction in breast cancer survivors.</h4><i>Yogeswaran V, Wadden E, Szewczyk W, Barac A, ... Cheng RK, Reding KW</i><br /><AbstractText>Advances in breast cancer (BC) treatment have contributed to improved survival, but BC survivors experience significant short-term and long-term cardiovascular mortality and morbidity, including an elevated risk of heart failure with preserved ejection fraction (HFpEF). Most research has focused on HF with reduced ejection fraction (HFrEF) after BC; however, recent studies suggest HFpEF is the more prevalent subtype after BC and is associated with substantial health burden. The increased HFpEF risk observed in BC survivors may be explained by treatment-related toxicity and by shared risk factors that heighten risk for both BC and HFpEF. Beyond risk factors with physiological impacts that drive HFpEF risk, such as hypertension and obesity, social determinants of health (SDOH) likely contribute to HFpEF risk after BC, impacting diagnosis, management and prognosis.Increasing clinical awareness of HFpEF after BC and screening for cardiovascular (CV) risk factors, in particular hypertension, may be beneficial in this high-risk population. When BC survivors develop HFpEF, treatment focuses on initiating guideline-directed medical therapy and addressing underlying comorbidities with pharmacotherapy or behavioural intervention. HFpEF in BC survivors is understudied. Future directions should focus on improving HFpEF prevention and treatment by building a deeper understanding of HFpEF aetiology and elucidating contributing risk factors and their pathogenesis in HFpEF in BC survivors, in particular the association with different BC treatment modalities, including radiation therapy, chemotherapy, biological therapy and endocrine therapy, for example, aromatase inhibitors. In addition, characterising how SDOH intersect with these therapies is of paramount importance to develop future prevention and management strategies.</AbstractText><br /><br />© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.<br /><br /><small>Heart: 31 May 2023; epub ahead of print</small></div>

<div><h4>Joint British Societies\' position statement on bullying, harassment and discrimination in cardiology.</h4><i>Camm CF, Joshi A, Eftekhari H, O\'Flynn R, ... Greenwood JP, Allen C</i><br /><AbstractText>Inappropriate behaviour is an umbrella term including discrimination, harassment and bullying. This includes both actions and language and can affect any member of the cardiovascular workforce/team. Evidence has suggested that such behaviour is regularly experienced within UK cardiology departments, where inappropriate behaviour may represent longstanding cultural and practice issues within the unit. Inappropriate behaviour has negative effects on the workforce community as a whole, including impacts on recruitment and retention of staff and patient care. While only some members of the cardiology team may be directly impacted by inappropriate behaviour in individual departments, a wider group are significantly impacted as bystanders. As such, improving the culture and professional behaviours within UK cardiology departments is of paramount importance. As a negative workplace culture is felt to be a major driver of inappropriate behaviour, all members of the cardiovascular team have a role to play in ensuring a positive workplace culture is developed. Episodes of inappropriate behaviour should be challenged by cardiovascular team members. Informal feedback may be appropriate where \'one-off\' episodes of inappropriate behaviour occur, but serious events or repeated behaviour should be escalated following formal human resources protocols.</AbstractText><br /><br />© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.<br /><br /><small>Heart: 30 May 2023; epub ahead of print</small></div>

<div><h4>Magnetic resonance analysis of ventricular volumes in bicuspid and trileaflet aortic regurgitation.</h4><i>Sevilla T, Rojas G, González-Bartol E, Candela J, ... Gomez Salvador I, San Román Calvar JA</i><br /><b>Objective</b><br />To identify differences in left ventricular (LV) remodelling between patients with bicuspid aortic valve (BAV) and trileaflet aortic valve (TAV) with chronic aortic regurgitation (AR).<br /><b>Methods</b><br />Retrospective cohort study of 210 consecutive patients undergoing cardiac magnetic resonance for AR evaluation. We divided the study population according to valvular morphology. Independent predictors of LV enlargement AR were evaluated.<br /><b>Results</b><br />There were 110 patients with BAV and 100 patients with TAV. Patients with BAV were younger (mean age BAV vs TAV: 41±16 years vs 67±11 years; p<0.01), mostly male (% male BAV vs TAV: 84.5% vs 65%, p=0.01) and presented milder degrees of AR (median regurgitant fraction BAV vs TAV: 14 (6-28)% vs 22 (12-35)%, p=0.002). Both groups presented similar indexed LV volumes and ejection fraction. According to the degree of AR, at mild AR, patients with BAV presented larger LV volumes (BAV vs TAV: indexed end diastolic left ventricular volumes (iEDV): 96.5±19.7 vs 82.1±19.3 mL, p<0.01; indexed end systolic left ventricular volumes (iESV): 39.4±10.3 mL vs 33.2±10.5 mL, p=0.01). These differences disappeared at higher degrees of AR. Independent predictors of LV enlargement were regurgitant fraction (EDV: OR 1.118 (1.081-1.156), p<0.001; ESV: OR 1.067 (1.042-1.092), p<0.001), age (EDV: OR 0.940 (0.917-0.964), p<0.001, ESV: OR 0.962 (0.945-0.979), p<0.001) and weight (EDV: OR 1.054 (1.025-1.083), p<0.001).<br /><b>Conclusions</b><br />In chronic AR, LV enlargement is an early finding. LV volumes display a direct correlation with regurgitant fraction and an inverse association with age. Patients with BAV present larger ventricular volumes, especially at mild AR. However, these differences are attributable to demographic disparities; valve type is not independently associated with LV size.<br /><br />© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.<br /><br /><small>Heart: 25 May 2023; epub ahead of print</small></div>

<div><h4>Prevalence of angina pectoris and association with coronary atherosclerosis in a general population.</h4><i>Welén Schef K, Tornvall P, Alfredsson J, Hagström E, ... Yndigegn T, Jernberg T</i><br /><b>Objective</b><br />To assess the contemporary prevalence of, and factors associated with angina pectoris symptoms, and to examine the relationship to coronary atherosclerosis in a middle-aged, general population.<br /><b>Methods</b><br />Data were based on the Swedish CArdioPulmonary bioImage Study (SCAPIS), in which 30 154 individuals were randomly recruited from the general population between 2013 and 2018. Participants that completed the Rose Angina Questionnaire were included and categorised as angina or no angina. Subjects with a valid coronary CT angiography (CCTA) were categorised by degree of coronary atherosclerosis; ≥50% obstruction (obstructive coronary atherosclerosis), <50% obstruction or any atheromatosis (non-obstructive coronary atherosclerosis) or none (no coronary atherosclerosis).<br /><b>Results</b><br />The study population consisted of 28 974 questionnaire responders (median age 57.4 years, female 51.6%, hypertension 19.9%, hyperlipidaemia 7.9%, diabetes mellitus 3.7%), of which 1025 (3.5%) fulfilled the criteria of angina. Coronary atherosclerosis was more common in individuals having angina compared with those with no angina (n=24 602, obstructive coronary atherosclerosis 11.8% vs 5.4%, non-obstructive coronary atherosclerosis 38.9% vs 37.0%, no coronary atherosclerosis 49.4% vs 57.7%, all p<0.001). Factors independently associated with angina were birthplace outside of Sweden (OR 2.58 (95% CI 2.10 to 2.92)), low educational level (OR 1.41 (1.10 to 1.79)), unemployment (OR 1.51 (1.27 to 1.81)), poor economic status (OR 1.85 (1.38 to 2.47)), symptoms of depression (OR 1.63 (1.38 to 1.92)) and high degree of stress (OR 2.92 (1.80 to 4.73)).<br /><b>Conclusion</b><br />Angina pectoris symptoms are common (3.5%) among middle-aged individuals of the general population of Sweden, though with low association to obstructive coronary atherosclerosis. Sociodemographic and psychological factors are highly associated with angina symptoms, irrespective of degree of coronary atherosclerosis.<br /><br />© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.<br /><br /><small>Heart: 23 May 2023; epub ahead of print</small></div>

<div><h4>Propensity-matched analysis of long-term clinical results after ostial circumflex revascularisation.</h4><i>Espejo-Paeres C, Vedia O, Wang L, Hennessey B, ... Escaned J, Jimenez-Quevedo P</i><br /><b>Background</b><br />Percutaneous coronary intervention (PCI) of the ostium of the left circumflex artery (LCx) is technically challenging. The aim of this study was to compare long-term clinical outcomes of ostial PCI located in the LCx versus the left anterior descending artery (LAD) in a propensity-matched population.<br /><b>Methods</b><br />Consecutive patients with a symptomatic isolated \'de novo\' ostial lesion of the LCx or LAD treated with PCI were included. Patients with a stenosis of >40% in the left main (LM) were excluded. A propensity score matching was performed to compare both groups. The primary endpoint was target lesion revascularisation (TLR); other endpoints included target lesion failure and an analysis of the bifurcation angles.<br /><b>Results</b><br />From 2004 to 2018, 287 consecutive patients with LAD (n=240) or LCx (n=47) ostial lesions treated with PCI were analysed. After the adjustment, 47 matched pairs were obtained. The mean age was 72±12 years and 82% were male. The LM-LAD angle was significantly wider than the LM-LCx angle (128°±23° vs 108°±24°, p=0.002). At a median follow-up of 5.5 (IQR 1.5-9.3) years, the rate of TLR was significantly higher in the LCx group (15% vs 2%); with an HR of 7.5, 95% CI 2.1 to 26.4, p<0.001. Interestingly, in the LCx group, TLR-LM occurred in 43% of the TLR cases; meanwhile, no TLR-LM involvement was found in the LAD group.<br /><b>Conclusions</b><br />Isolated ostial LCx PCI was associated with an increase in the rate of TLR compared with ostial LAD PCI at long-term follow-up. Larger studies evaluating the optimal percutaneous approach at this location are needed.<br /><br />© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.<br /><br /><small>Heart: 22 May 2023; epub ahead of print</small></div>

<div><h4>Validation of the TRI-SCORE in patients undergoing surgery for isolated tricuspid regurgitation.</h4><i>Anguita-Gámez M, Giraldo MA, Nombela-Franco L, Eixeres Esteve A, ... Maroto L, Carnero-Alcázar M</i><br /><b>Introduction</b><br />Estimation of peri-procedural risk in patients with tricuspid regurgitation (TR) undergoing isolated tricuspid valve surgery (ITVS) is of paramount importance. The TRI-SCORE is a new surgical risk scale specifically developed for this purpose, which ranged from 0 to 12 points and included eight parameters: right-sided heart failure signs, daily dose of furosemide ≥125 mg, glomerular filtration rate <30 mL/min, elevated bilirubin (with a value of 2 points), age ≥70 years, New York Heart Association Class III-IV, left ventricular ejection fraction <60% and moderate/severe right ventricular dysfunction (with a value of 1 point). The objective of the study was to evaluate the performance of the TRI-SCORE in an independent cohort of patients undergoing ITVS.<br /><b>Methods</b><br />A retrospective observational study was performed in four centres, including consecutive adult patients undergoing ITVS for TR between 2005 and 2022. The TRI-SCORE and the traditional risk scores used in cardiac surgery (Logistic EuroScore (Log-ES) and EuroScore-II (ES-II)) were applied for each patient, and discrimination and calibration of the three scores were evaluated in the entire cohort.<br /><b>Results</b><br />A total of 252 patients were included. The mean age was 61.5±11.2 years, 164 (65.1%) patients were female, and TR mechanism was functional in 160 (63.5%) patients. The observed in-hospital mortality was 10.3%. The estimated mortality by the Log-ES, ES-II and TRI-SCORE was 8.7±7.3%, 4.7±5.3% and 11.0±16.6%, respectively. Patients with a TRI-SCORE ≤4 and >4 had an in-hospital mortality of 1.3% and 25.0%, p=0.001, respectively. The discriminatory capacity of the TRI-SCORE had a C-statistic of 0.87 (0.81-0.92), which was significantly higher than both the Log-ES (0.65 (0.54-0.75)) and ES-II (0.67 (0.58-0.79)), p=0.001 (for both comparisons).<br /><b>Conclusion</b><br />This external validation of the TRI-SCORE demonstrated good performance to predict in-hospital mortality in patients undergoing ITVS, which was significantly better than the Log-ES and ES-II, which underestimated the observed mortality. These results support the widespread use of this score as a clinical tool.<br /><br />© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.<br /><br /><small>Heart: 22 May 2023; epub ahead of print</small></div>

<div><h4>Ambient air pollution and maternal cardiovascular health in pregnancy.</h4><i>Decrue F, Townsend R, Miller MR, Newby DE, Reynolds RM</i><br /><AbstractText>In this review, we summarise the current epidemiological and experimental evidence on the association of ambient (outdoor) air pollution exposure and maternal cardiovascular health during pregnancy. This topic is of utmost clinical and public health importance as pregnant women represent a potentially susceptible group due to the delicate balance of the feto-placental circulation, rapid fetal development and tremendous physiological adaptations to the maternal cardiorespiratory system during pregnancy.Several meta-analyses including up to 4 245 170 participants provide robust evidence that air pollutants, including particulate matter, nitrogen oxides and others, have adverse effects on the development of hypertensive disorders of pregnancy, gestational diabetes mellitus and cardiovascular events during labour. Potential underlying biological mechanisms include oxidative stress with subsequent endothelial dysfunction and vascular inflammation, β-cell dysfunction and epigenetic changes. Endothelial dysfunction can lead to hypertension by impairing vasodilatation and promoting vasoconstriction. Air pollution and the consequent oxidative stress can additionally accelerate β-cell dysfunction, which in turn triggers insulin resistance leading to gestational diabetes mellitus. Epigenetic changes in placental and mitochondrial DNA following air pollution exposures can lead to altered gene expression and contribute to placental dysfunction and induction of hypertensive disorders of pregnancy.The maternal and fetal consequences of such cardiovascular and cardiometabolic disease during pregnancy can be serious and long lasting, including preterm birth, increased risk of type 2 diabetes mellitus or cardiovascular disease later in life. Acceleration of efforts to reduce air pollution is therefore urgently needed to realise the full health benefits for pregnant mothers and their children.</AbstractText><br /><br />© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.<br /><br /><small>Heart: 22 May 2023; epub ahead of print</small></div>

<div><h4>Impact of clinical diagnosis of myocardial infarction in patients with elevated cardiac troponin.</h4><i>Gard A, Lindahl B, Baron T</i><br /><b>Objective</b><br />Type 2 myocardial infarction (MI) and myocardial injury are common conditions associated with an adverse prognosis. Physicians experience uncertainty how to distinguish these conditions, as well as how to manage and treat them. Therefore, the objective of this study was to compare treatment and prognosis in patients with an adjudicated diagnosis of type 2 MI and myocardial injury, who were discharged with and without a clinical diagnosis of MI.<br /><b>Design</b><br />The study consisted of two cohorts, 964 and 281 consecutive patients with elevated cardiac troponin, discharged with and without a clinical diagnosis of MI, respectively. All cases were adjudicated into MI type 1-5 or myocardial injury and followed regarding all-cause death.<br /><b>Results</b><br />The adjudication identified 138 and 37 cases of type 2 MI, and 86 and 185 of myocardial injury, with and without a clinical MI diagnosis, respectively. In patients with type 2 MI, a clinical MI diagnosis was associated with more coronary angiography investigations (39.1% vs 5.4%, p<0.001) and an increased use of secondary prevention medications (all p<0.001). However, no difference was observed in adjusted 5-year mortality between patients with and without a clinical MI diagnosis (HR: 0.77 with 95% CI 0.43 to 1.38). The results were similar for adjudicated myocardial injury.<br /><b>Conclusion</b><br />In both type 2 MI and myocardial injury, a clinical diagnosis of MI at discharge was associated with more investigations and treatments. However, no prognostic effect of receiving a clinical MI diagnosis was observed.<br /><br />© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.<br /><br /><small>Heart: 22 May 2023; epub ahead of print</small></div>

<div><h4>Mortality trends of aortic stenosis in high-income countries from 2000 to 2020.</h4><i>Hibino M, Pandey AK, Hibino H, Verma R, ... Pelletier MP, Verma S</i><br /><b>Objective</b><br />The purpose of this study is to describe recent mortality trends from aortic stenosis (AS) among eight high-income countries.<br /><b>Methods</b><br />We analysed the WHO mortality database to determine trends in mortality from AS in the UK, Germany, France, Italy, Japan, Australia, the USA and Canada from 2000 to 2020. Crude and age-standardised mortality rates per 100 000 persons were calculated. We calculated age-specific mortality rates in three groups (<64, 65-79 and ≥80 years). Annual percentage change was analysed using joinpoint regression.<br /><b>Results</b><br />During the observation period, the crude mortality rates per 100 000 persons increased in all the eight countries (from 3.47 to 5.87 in the UK, from 2.98 to 8.93 in Germany, from 3.84 to 5.52 in France, from 1.97 to 4.33 in Italy, from 1.12 to 5.49 in Japan, from 2.14 to 3.38 in Australia, from 3.58 to 4.22 in the USA and from 2.12 to 5.00 in Canada). In joinpoint regression of age-standardised mortality rates, trend changes towards a decrease were observed in Germany after 2012 (-1.2%, p=0.015), Australia after 2011 (-1.9%, p=0.005) and the USA after 2014 (-3.1%, p<0.001). Age-specific mortality rates in age group ≥80 years had shifts towards decreasing trends in all the eight countries in contrast to other younger age groups.<br /><b>Conclusions</b><br />While crude mortality rates increased in the eight countries, shifts towards decreasing trends were identified in age-standardised mortality rates in three countries and in the elderly aged ≥80 years in the eight countries. Further multidimensional observation is warranted to clarify the mortality trends.<br /><br />© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.<br /><br /><small>Heart: 19 May 2023; epub ahead of print</small></div>

<div><h4>Tolerability and beneficial effects of sacubitril/valsartan on systemic right ventricular failure.</h4><i>Nederend M, Kiès P, Regeer MV, Vliegen HW, ... Jongbloed MRM, Egorova AD</i><br /><b>Objective</b><br />Patients with a systemic right ventricle (sRV) in the context of transposition of the great arteries (TGA) after atrial switch or congenitally corrected TGA (ccTGA) are prone to sRV dysfunction. Pharmacological options for sRV failure remain poorly defined. This study aims to investigate the tolerability and effects of sacubitril/valsartan on sRV failure in adult patients with sRV.<br /><b>Methods</b><br />In this two-centre, prospective cohort study, all consecutive adult patients with symptomatic heart failure and at least moderately reduced sRV systolic function were initiated on sacubitril/valsartan and underwent structured follow-up.<br /><b>Results</b><br />Data of 40 patients were included (40% female, 30% ccTGA, median age 48 (44-53) years). Five patients discontinued therapy during titration. Median follow-up was 24 (12-36) months. The maximal dose was tolerated by 49% of patients. No episodes of hyperkalaemia or renal function decline occurred. Six-minute walking distance increased significantly after 6 months of treatment (569±16 to 597±16 m, p=0.016). Serum N-terminal-prohormone brain natriuretic peptide (NT-proBNP) levels decreased significantly after 3 months (567 (374-1134) to 404 (226-633) ng/L, p<0.001). Small, yet consistent echocardiographic improvements in sRV function were observed after 6 months (sRV global longitudinal strain: -11.1±0.5% to -12.6±0.7%, p<0.001, and fractional area change: 20% (16%-24%) to 26% (19%-30%), p<0.001). The linear mixed-effects model illustrated that after first follow-up moment, no time effect was present for the parameters.<br /><b>Conclusions</b><br />Treatment with sacubitril/valsartan was associated with a low rate of adverse effects in this adult sRV cohort. Persisting improvement in 6-minute walking test distance, NT-proBNP levels and echocardiographic parameters of sRV function was observed in an on-treatment analysis and showed no differential response based on sex or anatomy.<br /><br />© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.<br /><br /><small>Heart: 11 May 2023; epub ahead of print</small></div>

<div><h4>Aortic sodium [F]fluoride uptake following endovascular aneurysm repair.</h4><i>Debono S, Nash J, Fletcher AJ, Syed M, ... Newby DE, Forsythe RO</i><br /><b>Objective</b><br />In patients with abdominal aortic aneurysms, sodium [<sup>18</sup>F]fluoride positron emission tomography identifies aortic microcalcification and disease activity. Increased uptake is associated with aneurysm expansion and adverse clinical events. The effect of endovascular aneurysm repair (EVAR) on aortic disease activity and sodium [<sup>18</sup>F]fluoride uptake is unknown. This study aimed to compare aortic sodium [<sup>18</sup>F]fluoride uptake before and after treatment with EVAR.<br /><b>Methods</b><br />In a preliminary proof-of-concept cohort study, preoperative and post-operative sodium [<sup>18</sup>F]fluoride positron emission tomography-computed tomography angiography was performed in patients with an infrarenal abdominal aortic aneurysm undergoing EVAR according to current guideline-directed size treatment thresholds. Regional aortic sodium [<sup>18</sup>F]fluoride uptake was assessed using aortic microcalcification activity (AMA): a summary measure of mean aortic sodium [<sup>18</sup>F]fluoride uptake.<br /><b>Results</b><br />Ten participants were recruited (76±6 years) with a mean aortic diameter of 57±2 mm at time of EVAR. Mean time from EVAR to repeat scan was 62±21 months. Prior to EVAR, there was higher abdominal aortic AMA when compared with the thoracic aorta (AMA 1.88 vs 1.2; p<0.001). Following EVAR, sodium [<sup>18</sup>F]fluoride uptake was markedly reduced in the suprarenal (ΔAMA 0.62, p=0.03), neck (ΔAMA 0.72, p=0.02) and body of the aneurysm (ΔAMA 0.69, p=0.02) while it remained unchanged in the thoracic aorta (ΔAMA 0.11, p=0.41).<br /><b>Conclusions</b><br />EVAR is associated with a reduction in AMA within the stented aortic segment. This suggests that EVAR can modify aortic disease activity and aortic sodium [<sup>18</sup>F]fluoride uptake is a promising non-invasive surrogate measure of aneurysm disease activity.<br /><br />© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY. Published by BMJ.<br /><br /><small>Heart: 10 May 2023; epub ahead of print</small></div>

<div><h4>Pregnancy-related aortic complications in women with bicuspid aortic valve.</h4><i>Galian-Gay L, Pijuan-Domenech A, Cantalapiedra-Romero J, Serrano B, ... Rodriguez-Palomares JF, Ferreira-Gonzalez I</i><br /><b>Objectives</b><br />To describe the aortic-related risks associated with pregnancy in women with bicuspid aortic valve (BAV) and to evaluate changes in aortic diameter in pregnancy.<br /><b>Methods</b><br />Prospective observational study of patients with BAV from a single-site registry of pregnant women with structural heart disease between 2013 and 2020. Cardiac, obstetric and neonatal outcomes were studied. An assessment of aortic dimensions was performed during pregnancy by two-dimensional echocardiography. Aortic diameters were measured at the annulus, root, sinotubular junction and maximum ascending aorta diameter, and the largest diameter was used. Measurements of the aorta were made using the end-diastolic leading edge-to-leading edge convention.<br /><b>Results</b><br />Forty-three women (32.9 years, IQR 29.6-35.3) with BAV were included: 9 (20.9%) had repaired aortic coarctation; 23 (53.5%) had moderate or severe aortic valve disease; 5 (11.6%) had a bioprosthetic aortic valve; and 2 (4.7%) had a mechanical prosthetic aortic valve. Twenty (47.0%) were nulliparous. The mean aortic diameter in the first trimester was 38.5 (SD 4.9) mm, and that in the third trimester was 38.4 (SD 4.8) mm. Forty (93.0%) women had an aortic diameter of <45 mm; 3 (7.0%) had 45-50 mm; and none had >50 mm. Three women (6.9%) with BAV presented cardiovascular complications during pregnancy or the postpartum period (two prosthetic thrombosis and one heart failure). No aortic complications were reported. There was a small but significant increase in aortic diameter during pregnancy (third trimester vs first trimester, 0.52 (SD 1.08) mm; p=0.03). Obstetric complications appeared in seven (16.3%) of pregnancies, and there were no maternal deaths. Vaginal non-instrumental delivery was performed in 21 (51.2%) out of 41 cases. There were no neonatal deaths, and the mean newborn weight was 3130 g (95% CI 2652 to 3380).<br /><b>Conclusions</b><br />Pregnancy in BAV women had a low rate of cardiac complications with no aortic complications observed in a small study group. Neither aortic dissection nor need for aortic surgery was reported. A low but significant aortic growth was observed during pregnancy. Although requiring follow-up, the risk of aortic complications in pregnant women with BAV and aortic diameters of <45 mm at baseline is low.<br /><br />© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.<br /><br /><small>Heart: 05 May 2023; epub ahead of print</small></div>

<div><h4>Impact of cardiac surgery on left-sided infective endocarditis with intermediate-length vegetations.</h4><i>Scheggi V, Bohbot Y, Tribouilloy C, Trojette F, ... Habib G, Marchionni N</i><br /><b>Objective</b><br />The best strategy to manage patients with left-sided infective endocarditis (IE) and intermediate-length vegetations (10-15 mm) remains uncertain. We aimed to evaluate the role of surgery in patients with intermediate-length vegetations and no other European Society of Cardiology guidelines-approved surgical indication.<br /><b>Methods</b><br />We retrospectively enrolled 638 consecutive patients admitted to three academic centres (Amiens, Marseille and Florence University Hospitals) between 2012 and 2022 for left-sided definite IE (native or prosthetic) with intermediate-length vegetations (10-15 mm). We compared four clinical groups: medically (n=50) or surgically (n=345) treated complicated IE, medically (n=194) or surgically (n=49) treated uncomplicated IE.<br /><b>Results</b><br />Mean age was 67±14 years. Women were 182 (28.6%). The rate of embolic events on admission was 40% in medically treated and 61% in surgically treated complicated IE, 31% in medically treated and 26% in surgically treated uncomplicated IE. The analysis of all-cause mortality showed the lowest 5-year survival rate for medically treated complicated IE (53.7%). We found a similar 5-year survival rate for surgically treated complicated IE (71.4%) and medically treated uncomplicated IE (68.4%). The highest 5-year survival rate was observed in surgically treated uncomplicated IE group (82.4%, log-rank p<0.001). The analysis of the propensity score-matched cohort estimated an HR of 0.23 for uncomplicated IE treated surgically compared with medical therapy (p=0.005, 95% CI: 0.079 to 0.656).<br /><b>Conclusions</b><br />Our results suggest that surgery is associated with lower all-cause mortality than medical therapy in patients with uncomplicated left-sided IE with intermediate-length vegetations even in the absence of other guideline-based indications.<br /><br />© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.<br /><br /><small>Heart: 05 May 2023; epub ahead of print</small></div>

<div><h4>Transcatheter aortic valve intervention in patients with cancer.</h4><i>Leedy D, Elison DM, Farias F, Cheng R, McCabe JM</i><br /><AbstractText>The prevalence of concurrent cancer and severe aortic stenosis (AS) is increasing due to an ageing population. In addition to shared traditional risk factors for AS and cancer, patients with cancer may be at increased risk for AS due to off-target effects of cancer-related therapy, such as mediastinal radiation therapy (XRT), as well as shared non-traditional pathophysiological mechanisms. Compared with surgical aortic valve replacement, major adverse events are generally lower in patients with cancer undergoing transcatheter aortic valve intervention (TAVI), especially in those with history of mediastinal XRT. Similar procedural and short-to-intermediate TAVI outcomes have been observed in patients with cancer as compared with no cancer, whereas long-term outcomes are dependent on cancer survival. Considerable heterogeneity exists between cancer subtypes and stage, with worse outcomes observed in those with active and advanced-stage disease as well as specific cancer subtypes. Procedural management in patients with cancer poses unique challenges and thus requires periprocedural expertise and close collaboration with the referring oncology team. The decision to ultimately pursue TAVI involves a multidisciplinary and holistic approach in assessing the appropriateness of intervention. Further clinical trial and registry studies are needed to better appreciate outcomes in this population.</AbstractText><br /><br />© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.<br /><br /><small>Heart: 05 May 2023; epub ahead of print</small></div>

<div><h4>Effect of race on pressure recovery adjustment for prevention of aortic stenosis grading discordance.</h4><i>Oh JK, Shen M, Guzzetti E, Tastet L, ... Clavel MA, Song JK</i><br /><b>Objective</b><br />We sought to evaluate the potential impact of racial difference (Asians vs Caucasians) on the clinical usefulness of pressure recovery (PR) adjustment for preventing discordant aortic stenosis (AS) grading in patients with severe AS.<br /><b>Methods</b><br />Data from 1450 patients (mean age, 70.2±10.6 years; 290 (20%) Caucasians; aortic valve area (AVA), 0.77±0.26 cm<sup>2</sup>) were retrospectively analysed. PR-adjusted AVA was calculated using a validated equation. Discordant grading of severe AS was defined as AVA of <1.0 cm<sup>2</sup> and mean gradient of <40 mm Hg. The frequency of discordant grading was assessed in the overall cohort and the propensity score-matched cohort.<br /><b>Results</b><br />Before PR adjustment, 1186 patients showed AVA values of <1.0 cm<sup>2</sup>; after PR adjustment, 170 (14.3%) were reclassified as having moderate AS. PR adjustment decreased the frequency of discordant grading from 31.4% to 14.1% in Caucasians and from 13.8% to 7.9% in Asians. Patients with reclassification to moderate AS after PR adjustment had a significantly lower risk of a composite of aortic valve replacement or all-cause death than did those with severe AS after PR adjustment (HR 0.38; 95% CI 0.31-0.46; p<0.001). In propensity score-matched cohorts (173 pairs), the frequency of discordant grading before PR adjustment was 42.2% and 43.9% in the Caucasian and Asian patients, respectively, which decreased to 21.4% and 20.2%, respectively, after PR adjustment.<br /><b>Conclusions</b><br />Clinically relevant PR occurred, regardless of race in patients with moderate to severe AS. Routine PR adjustment may be useful for reconciling discordant AS grading.<br /><br />© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.<br /><br /><small>Heart: 05 May 2023; epub ahead of print</small></div>

<div><h4>Rationale and design of a randomised trial of trientine in patients with hypertrophic cardiomyopathy.</h4><i>Farrant J, Dodd S, Vaughan C, Reid A, ... Miller CA, TEMPEST investigators</i><br /><b>Aims</b><br />Hypertrophic cardiomyopathy (HCM) is characterised by left ventricular hypertrophy (LVH), myocardial fibrosis, enhanced oxidative stress and energy depletion. Unbound/loosely bound tissue copper II ions are powerful catalysts of oxidative stress and inhibitors of antioxidants. Trientine is a highly selective copper II chelator. In preclinical and clinical studies in diabetes, trientine is associated with reduced LVH and fibrosis, and improved mitochondrial function and energy metabolism. Trientine was associated with improvements in cardiac structure and function in an open-label study in patients with HCM.<br /><b>Methods</b><br />The Efficacy and Mechanism of Trientine in Patients with Hypertrophic Cardiomyopathy (TEMPEST) trial is a multicentre, double-blind, parallel group, 1:1 randomised, placebo-controlled phase II trial designed to evaluate the efficacy and mechanism of action of trientine in patients with HCM. Patients with a diagnosis of HCM according to the European Society of Cardiology Guidelines and in New York Heart Association classes I-III are randomised to trientine or matching placebo for 52 weeks. Primary outcome is change in left ventricular (LV) mass indexed to body surface area, measured using cardiovascular magnetic resonance. Secondary efficacy objectives will determine whether trientine improves exercise capacity, reduces arrhythmia burden, reduces cardiomyocyte injury, improves LV and atrial function, and reduces LV outflow tract gradient. Mechanistic objectives will determine whether the effects are mediated by cellular or extracellular mass regression and improved myocardial energetics.<br /><b>Conclusion</b><br />TEMPEST will determine the efficacy and mechanism of action of trientine in patients with HCM.<br /><b>Trial registration numbers</b><br />NCT04706429 and ISRCTN57145331.<br /><br />© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY. Published by BMJ.<br /><br /><small>Heart: 03 May 2023; epub ahead of print</small></div>

<div><h4>Association of beta-blockers beyond 1 year after myocardial infarction and cardiovascular outcomes.</h4><i>Ishak D, Aktaa S, Lindhagen L, Alfredsson J, ... Gale CP, Batra G</i><br /><b>Objective</b><br />Beta-blockers (BB) are an established treatment following myocardial infarction (MI). However, there is uncertainty as to whether BB beyond the first year of MI have a role in patients without heart failure or left ventricular systolic dysfunction (LVSD).<br /><b>Methods</b><br />A nationwide cohort study was conducted including 43 618 patients with MI between 2005 and 2016 in the Swedish register for coronary heart disease. Follow-up started 1 year after hospitalisation (index date). Patients with heart failure or LVSD up until the index date were excluded. Patients were allocated into two groups according to BB treatment. Primary outcome was a composite of all-cause mortality, MI, unscheduled revascularisation and hospitalisation for heart failure. Outcomes were analysed using Cox and Fine-Grey regression models after inverse propensity score weighting.<br /><b>Results</b><br />Overall, 34 253 (78.5%) patients received BB and 9365 (21.5%) did not at the index date 1 year following MI. The median age was 64 years and 25.5% were female. In the intention-to-treat analysis, the unadjusted rate of primary outcome was lower among patients who received versus not received BB (3.8 vs 4.9 events/100 person-years) (HR 0.76; 95% CI 0.73 to 1.04). Following inverse propensity score weighting and multivariable adjustment, the risk of the primary outcome was not different according to BB treatment (HR 0.99; 95% CI 0.93 to 1.04). Similar findings were observed when censoring for BB discontinuation or treatment switch during follow-up.<br /><b>Conclusion</b><br />Evidence from this nationwide cohort study suggests that BB treatment beyond 1 year of MI for patients without heart failure or LVSD was not associated with improved cardiovascular outcomes.<br /><br />© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.<br /><br /><small>Heart: 02 May 2023; epub ahead of print</small></div>

<div><h4>Assessment of haemoglobin and serum markers of iron deficiency in people with cardiovascular disease.</h4><i>Graham FJ, Friday JM, Pellicori P, Greenlaw N, Cleland JG</i><br /><b>Background</b><br />The prevalence of anaemia and iron deficiency and their prognostic association with cardiovascular disease have rarely been explored at population level.<br /><b>Methods</b><br />National Health Service records of the Greater Glasgow region for patients aged ≥50 years with a broad range of cardiovascular diagnoses were obtained. During 2013/14, prevalent disease was identified and results of investigations collated. Anaemia was defined as haemoglobin <13 g/dL for men or <12 g/dL for women. Incident heart failure, cancer and death between 2015 and 2018 were identified.<br /><b>Results</b><br />The 2013/14 dataset comprised 197 152 patients, including 14 335 (7%) with heart failure. Most (78%) patients had haemoglobin measured, especially those with heart failure (90%). Of those tested, anaemia was common both in patients without (29%) and with heart failure (prevalent cases in 2013/14: 46%; incident cases during 2013/14: 57%). Ferritin was usually measured only when haemoglobin was markedly depressed; transferrin saturation (TSAT) even less often. Incidence rates for heart failure and cancer during 2015-18 were inversely related to nadir haemoglobin in 2013/14. A haemoglobin of 13-15 g/dL for women and 14-16 g/dL for men was associated with the lowest mortality. Low ferritin was associated with a better prognosis and low TSAT with a worse prognosis.<br /><b>Conclusion</b><br />In patients with a broad range of cardiovascular disorders, haemoglobin is often measured but, unless anaemia is severe, markers of iron deficiency are usually not. Low haemoglobin and TSAT, but not low ferritin, are associated with a worse prognosis. The nadir of risk occurs at haemoglobin 1-3 g/dL above the WHO definition of anaemia.<br /><br />© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY. Published by BMJ.<br /><br /><small>Heart: 02 May 2023; epub ahead of print</small></div>

<div><h4>Coronary artery calcium: from risk prediction to treatment allocation and clinical trials.</h4><i>Whelton SP, Blaha MJ</i><br /><AbstractText>Coronary artery calcium (CAC) is a direct measure of an individual\'s coronary atherosclerotic burden. Higher levels of CAC are strongly associated with an increased risk of cardiovascular disease (CVD) events and individuals with very high CAC levels have a CVD risk similar to stable persons with a prior CVD event. Conversely, the absence of CAC (CAC=0) is associated with a low long-term risk of CVD, even among groups classified as high risk based on traditional risk factors. Accordingly, the guideline-based role of CAC in allocation of CVD prevention therapies has expanded to include both statin and non-statin medications. Beyond prevention therapies, it is now widely recognised that the total burden of atherosclerosis is a stronger risk factor for CVD than a sole focus on coronary stenosis. Furthermore, evidence is accruing to support expanding the value of CAC=0 among low-risk symptomatic patients given its very high negative predictive value for ruling out obstructive coronary artery disease. There is now an appreciation of the value of routine assessment of CAC on all non-gated chest CTs and with the advent of artificial intelligence, automated interpretation is now possible. Additionally, CAC is now firmly established in randomised trials as a tool to identify high-risk patients most likely to benefit from pharmacotherapies. Future studies incorporating measures of atherosclerosis beyond the Agatston score will lead to continued refinement of CAC scoring, further improvements in personalisation of CVD risk prediction and more individualised allocation of prevention therapies to the patients at highest CVD risk.</AbstractText><br /><br />© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.<br /><br /><small>Heart: 02 May 2023; epub ahead of print</small></div>

<div><h4>Morpho-mechanistic screening criteria for the echocardiographic detection of rheumatic heart disease.</h4><i>Hunter LD, Doubell AF, Pecoraro AJK, Monaghan M, ... Lombard C, Herbst PG</i><br /><b>Introduction</b><br />Screening echocardiography, guided by the current World Heart Federation (WHF) criteria, has important limitations that impede the establishment of large-scale rheumatic heart disease (RHD) control programmes in endemic regions. The criteria misclassify a significant number of normal cases as borderline RHD. Prior attempts to simplify them are limited by incorporation bias due to the lack of an externally validated, accurate diagnostic test for RHD. We set out to assess novel screening criteria designed to avoid incorporation bias and to compare this against the performance of the current WHF criteria.<br /><b>Methods</b><br />The performance of the WHF and the morpho-mechanistic (MM) RHD screening criteria (a novel set of screening criteria that evaluate leaflet morphology, motion and mechanism of regurgitation) as well as a simplified RHD MM \'rule-out\' test (based on identifying a predefined sign of anterior mitral valve leaflet restriction for the mitral valve and any aortic regurgitation for the aortic valve) were assessed in two contrasting cohorts: first, a low-risk RHD cohort consisting of children with a very low-risk RHD profile. and second, a composite reference standard (CRS) RHD-positive cohort that was created using a composite of two criteria to ensure a cohort with the highest possible likelihood of RHD. Subjects included in this group required (1) proven, prior acute rheumatic fever and (2) current evidence of predefined valvular regurgitation on echocardiography.<br /><b>Results</b><br />In the low-risk RHD cohort (n=364), the screening specificities for detecting RHD of the MM and WHF criteria were 99.7% and 95.9%, respectively (p=0.0002). The MM rule-out test excluded 359/364 cases (98.6%). In the CRS RHD-positive cohort (n=65), the screening sensitivities for the detection of definite RHD by MM and WHF criteria were 92.4% and 89.2%, respectively (p=0.2231). The MM RHD rule-out test did not exclude any cases from the CRS RHD-positive cohort.<br /><b>Conclusion</b><br />Our proposed MM approach showed an equal sensitivity to the WHF criteria but with significantly improved specificity. The MM RHD rule-out test excluded RHD-negative cases while identifying all cases within the CRS RHD-positive cohort. This holds promise for the development of a two-step RHD screening algorithm to enable task shifting in RHD endemic regions.<br /><br />© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.<br /><br /><small>Heart: 28 Apr 2023; epub ahead of print</small></div>

<div><h4>Sex differences in clinical characteristics and prognosis of patients with cardiac sarcoidosis.</h4><i>Iso T, Maeda D, Matsue Y, Dotare T, ... Baba Y, Minamino T</i><br /><b>Objective</b><br />Owing to the paucity of data, this study aimed to investigate sex differences in clinical features and prognosis of patients with cardiac sarcoidosis (CS).<br /><b>Methods</b><br />This study was a secondary analysis of the ILLUstration of the Management and prognosIs of JapaNese PATiEnts with Cardiac Sarcoidosis registry-a retrospective multicentre registry that enrolled patients with CS between 2001 and 2017. The primary outcome was potentially fatal ventricular arrhythmia events (pFVAEs)-a composite of sudden cardiac death, sustained ventricular tachycardia lasting >30 s, ventricular fibrillation or the requirement for implantable cardioverter defibrillator therapy.<br /><b>Results</b><br />Of the 512 participants (mean age±SD 61.6±11.4 years), 329 (64.2%) were females. Both sexes had peak ages of 60-64 years at diagnosis. Male patients were younger and had a higher prevalence of coronary artery disease and lower left ventricular ejection fraction than female patients. During a median follow-up of 3 years (IQR 1.6-5.6), pFVAEs were observed in 99 patients, with males having a significantly higher risk than females (p=0.002). This association was retained even after adjustment for other risk factors for pFVAEs, including left ventricular ejection fraction (adjusted HR 1.80; 95% CI 1.08 to 3.01, p=0.025).<br /><b>Conclusion</b><br />Approximately two-thirds of patients with CS were females, with a peak age of approximately 60 years at clinical diagnosis in both sexes; male patients were younger than female patients. Male patients had a significantly higher risk of pFVAEs than female patients.<br /><b>Trial registration number</b><br />UMIN000034974.<br /><br />© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.<br /><br /><small>Heart: 25 Apr 2023; epub ahead of print</small></div>

<div><h4>Chest pain symptoms during myocardial infarction in patients with and without diabetes: a systematic review and meta-analysis.</h4><i>Kumar A, Sanghera A, Sanghera B, Mohamed T, ... Marston L, Jones MM</i><br /><b>Objective</b><br />Chest pain (CP) is key in diagnosing myocardial infarction (MI). Patients with diabetes mellitus (DM) are at increased risk of an MI but may experience less CP, leading to delayed treatment and worse outcomes. We compared the prevalence of CP in those with and without DM who had an MI.<br /><b>Methods</b><br />The study population was people with MI presenting to healthcare services. The outcome measure was the absence of CP during MI, comparing those with and without DM. Medline and Embase databases were searched to 18 October 2021, identifying 9272 records. After initial independent screening, 87 reports were assessed for eligibility against the inclusion criteria, quality and risk of bias assessment (Strengthening the Reporting of Observational Studies in Epidemiology and Newcastle-Ottawa criteria), leaving 22 studies. The meta-analysis followed Meta-analysis Of Observational Studies in Epidemiology criteria and reported according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Pooled ORs, weights and 95% CIs were calculated using a random-effects model.<br /><b>Results</b><br />This meta-analysis included 232 519 participants from 22 studies and showed an increased likelihood of no CP during an MI for those with DM, compared with those without. This was 43% higher in patients with DM in the cohort and cross-sectional studies (OR: 1.43; 95% CI: 1.26 to 1.62), and 44% higher in case-control studies (OR: 1.44; 95% CI: 1.11 to 1.87).<br /><b>Conclusion</b><br />In patients with an MI, patients with DM are less likely than those without to have presentations with CP recorded. Clinicians should consider an MI diagnosis when patients with DM present with atypical symptoms and treatment protocols should reflect this, alongside an increased patient awareness on this issue.<br /><b>Prospero registration number</b><br />CRD42017058223.<br /><br />© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.<br /><br /><small>Heart: 20 Apr 2023; epub ahead of print</small></div>

<div><h4>Impact on stable chest pain pathways of CT fractional flow reserve.</h4><i>O\'Leary RA, Burn J, Urwin SG, Sims AJ, Beattie A, Bagnall A</i><br /><b>Objectives</b><br />To evaluate the impact of introducing CT fractional flow reserve (FFR<sub>CT</sub>) on stable chest pain pathways, concordance with National Institute for Health and Care Excellence (NICE) chest pain guidelines, resource usage and revascularisation of patients from a tertiary UK cardiac centre rapid access chest pain clinic (RACPC).<br /><b>Methods</b><br />Single-centre before and after study comparing data from electronic records and Strategic Tracing Service of all RACPC patients attending between 1 July 2017 and 31 December 2017, and 1 August 2018 and 31 January 2019.<br /><b>Results</b><br />Two hundred and sixty-eight and 287 patients (overall mean age 62 years, range 26-89 years, 48.3% male), were eligible for first-line CT coronary angiography (CTCA) pre-FFR<sub>CT</sub> and post-FFR<sub>CT</sub>, respectively. First-line CTCA use per NICE Guideline CG95 increased (50.6% pre-FFR<sub>CT</sub> vs 75.7% post-FFR<sub>CT</sub>, p<0.001). More patients reached pathway endpoint (revascularisation or assumed medical management) after one investigation (74.9% pre-FFR<sub>CT</sub> vs 84.9% post-FFR<sub>CT</sub>, p=0.005). There were fewer stress (22.8% pre-FFR<sub>CT</sub> vs 7.7% post-FFR<sub>CT</sub>, p<0.001) and rest (10.4% pre-FFR<sub>CT</sub> vs 4.2% post-FFR<sub>CT</sub>, p=0.007) myocardial perfusion scans and diagnostic-only angiograms (25.5% vs 13.7%, p<0.001). Despite fewer invasive procedures (29.3% pre-FFR<sub>CT</sub> vs 17.6% post-FFR<sub>CT</sub>, p=0.002), revascularisation rates remained similar (10.4% pre-FFR<sub>CT</sub> vs 8.8% post-FFR<sub>CT</sub>, p=0.561). Avoiding invasive investigations reduced inpatient admissions (39.0% pre-FFR<sub>CT</sub> vs 24.3% post-FFR<sub>CT</sub>, p<0.001). Time to revascularisation was unchanged (153.5 days pre-FFR<sub>CT</sub> vs 142.0 post-FFR<sub>CT</sub>, p=0.925). Unplanned hospital attendances, emergency admissions and adverse events were similar.<br /><b>Conclusions</b><br />FFR<sub>CT</sub> adoption was associated with greater compliance with NICE guidelines, reduced invasive diagnostic angiography, planned admissions and needing more than one test to reach a pathway endpoint.<br /><br />© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.<br /><br /><small>Heart: 20 Apr 2023; epub ahead of print</small></div>

<div><h4>Systolic blood pressure, chronic obstructive pulmonary disease and cardiovascular risk.</h4><i>Rao S, Nazarzadeh M, Li Y, Canoy D, ... Salimi-Khorshidi G, Rahimi K</i><br /><b>Objective</b><br />In individuals with complex underlying health problems, the association between systolic blood pressure (SBP) and cardiovascular disease is less well recognised. The association between SBP and risk of cardiovascular events in patients with chronic obstructive pulmonary disease (COPD) was investigated.<br /><b>Methods and analysis</b><br />In this cohort study, 39 602 individuals with a diagnosis of COPD aged 55-90 years between 1990 and 2009 were identified from validated electronic health records (EHR) in the UK. The association between SBP and risk of cardiovascular end points (composite of ischaemic heart disease, heart failure, stroke and cardiovascular death) was analysed using a deep learning approach.<br /><b>Results</b><br />In the selected cohort (46.5% women, median age 69 years), 10 987 cardiovascular events were observed over a median follow-up period of 3.9 years. The association between SBP and risk of cardiovascular end points was found to be monotonic; the lowest SBP exposure group of <120 mm Hg presented nadir of risk. With respect to reference SBP (between 120 and 129 mm Hg), adjusted risk ratios for the primary outcome were 0.99 (95% CI 0.93 to 1.05) for SBP of <120 mm Hg, 1.02 (0.97 to 1.07) for SBP between 130 and 139 mm Hg, 1.07 (1.01 to 1.12) for SBP between 140 and 149 mm Hg, 1.11 (1.05 to 1.17) for SBP between 150 and 159 mm Hg and 1.16 (1.10 to 1.22) for SBP ≥160 mm Hg.<br /><b>Conclusion</b><br />Using deep learning for modelling EHR, we identified a monotonic association between SBP and risk of cardiovascular events in patients with COPD.<br /><br />© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY. Published by BMJ.<br /><br /><small>Heart: 20 Apr 2023; epub ahead of print</small></div>

<div><h4>Incident cardiovascular events and imaging phenotypes in UK Biobank participants with past cancer.</h4><i>Raisi-Estabragh Z, Cooper J, McCracken C, Crosbie EJ, ... Neubauer S, Petersen SE</i><br /><b>Objectives</b><br />To evaluate incident cardiovascular outcomes and imaging phenotypes in UK Biobank participants with previous cancer.<br /><b>Methods</b><br />Cancer and cardiovascular disease (CVD) diagnoses were ascertained using health record linkage. Participants with cancer history (breast, lung, prostate, colorectal, uterus, haematological) were propensity matched on vascular risk factors to non-cancer controls. Competing risk regression was used to calculate subdistribution HRs (SHRs) for associations of cancer history with incident CVD (ischaemic heart disease (IHD), non-ischaemic cardiomyopathy (NICM), heart failure (HF), atrial fibrillation/flutter, stroke, pericarditis, venous thromboembolism (VTE)) and mortality outcomes (any CVD, IHD, HF/NICM, stroke, hypertensive disease) over 11.8±1.7 years of prospective follow-up. Linear regression was used to assess associations of cancer history with left ventricular (LV) and left atrial metrics.<br /><b>Results</b><br />We studied 18 714 participants (67% women, age: 62 (IQR: 57-66) years, 97% white ethnicities) with cancer history, including 1354 individuals with cardiovascular magnetic resonance. Participants with cancer had high burden of vascular risk factors and prevalent CVDs. Haematological cancer was associated with increased risk of all incident CVDs considered (SHRs: 1.92-3.56), larger chamber volumes, lower ejection fractions, and poorer LV strain. Breast cancer was associated with increased risk of selected CVDs (NICM, HF, pericarditis and VTE; SHRs: 1.34-2.03), HF/NICM death, hypertensive disease death, lower LV ejection fraction, and lower LV global function index. Lung cancer was associated with increased risk of pericarditis, HF, and CVD death. Prostate cancer was linked to increased VTE risk.<br /><b>Conclusions</b><br />Cancer history is linked to increased risk of incident CVDs and adverse cardiac remodelling independent of shared vascular risk factors.<br /><br />© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY. Published by BMJ.<br /><br /><small>Heart: 18 Apr 2023; epub ahead of print</small></div>

<div><h4>Prevalence of pulmonary hypertension in aortic stenosis and its influence on outcomes.</h4><i>Ratwatte S, Stewart S, Strange G, Playford D, Celermajer DS</i><br /><b>Objective</b><br />The significance of pulmonary hypertension (PHT) complicating aortic stenosis (AS) is poorly characterised. In a large cohort of adults with at least moderate AS, we aimed to describe the prevalence and prognostic importance of PHT in such patients.<br /><b>Methods</b><br />In this retrospective study, we analysed the National Echocardiography Database of Australia (data from 2000 to 2019). Adults with an estimated right ventricular systolic pressure (eRVSP), left ventricular ejection fraction (LVEF) >50% and with moderate or greater AS were included (n=14 980). These subjects were then categorised according to their eRVSP. The relationship between PHT severity and mortality outcomes were evaluated (median follow-up of 2.6 years, IQR 1.0-4.6 years).<br /><b>Results</b><br />Subjects were aged 77±13 years and 57.4% were female. Overall, 2049 (13.7%), 5085 (33.9%), 4380 (29.3%), 1956 (13.1%) and 1510 (10.1%) patients had no (eRVSP<30.00 mm Hg), borderline (30.00-39.99 mm Hg), mild (40.00-49.99 mm Hg), moderate (50.00-59.99 mm Hg) and severe PHT (>60.00 mm Hg), respectively. An echocardiographic phenotype was evident with worsening PHT, showing rising E:e\' ratio and right and left atrial sizes(p<0.0001, for all). Adjusted analyses showed that the risk of long-term mortality progressively rose as eRVSP level increased (HR 1.14-2.94, borderline to severe PHT, p<0.0001 for all). A mortality threshold was identified in the 4th decile of eRVSP categories (35.01-38.00 mm Hg; HR 1.19, 95% CI 1.04 to 1.35), with risk progressively increasing through to the 10th decile (HR 2.86, 95% CI 2.54 to 3.21).<br /><b>Conclusions</b><br />In this large cohort study, we find that PHT is common in ≥moderate AS and mortality increases as PHT becomes more severe. A threshold for higher mortality lies within the range of \'borderline-mild\' PHT.<br /><b>Trial registration number</b><br />ACTRN12617001387314.<br /><br />© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.<br /><br /><small>Heart: 03 Apr 2023; epub ahead of print</small></div>

<div><h4>Prevalence of pulmonary hypertension in aortic regurgitation and its influence on outcomes.</h4><i>Ratwatte S, Playford D, Stewart S, Strange G, Celermajer DS</i><br /><b>Objective</b><br />Aortic regurgitation (AR) can lead to pulmonary hypertension (PHT). There is a paucity of data on the prognostic importance of PHT in these patients. We therefore aimed to describe the prevalence and prognostic importance of PHT in such patients.<br /><b>Methods</b><br />In this retrospective study, we analysed the National Echocardiography Database of Australia (data from 2000 to 2019). Adults with an estimated right ventricular systolic pressure (eRVSP), left ventricular ejection fraction (LVEF) >50% and with moderate or greater AR were included (n=8392). These subjects were then categorised according to their eRVSP. The relationship between PHT severity and mortality outcomes were evaluated (median follow-up of 3.1 years, IQR 1.5-5.7 years).<br /><b>Results</b><br />Subjects were aged 74±14 years and 58.4% (4901) were female. Overall, 1417 (16.9%) had no PHT, and 3253 (38.8%), 2249 (26.9%), 893 (10.6%) and 580 (6.9%) patients had borderline, mild, moderate and severe PHT, respectively. Mean eRVSP was slightly higher in females than males (41±13 vs 39±12 mm Hg, p<0.0001) and increased with age in both sexes. After adjustment for age and sex, the risk of long-term mortality increased as eRVSP increased (adjusted HR (aHR) 1.20, 95% CI 1.06 to 1.36 in borderline PHT, to aHR 3.32, 95% CI 2.85 to 3.86 in severe PHT, p<0.0001). There was a mortality threshold seen from mild PHT onwards (eRVSP 41.36-44.15 mm Hg; aHR 1.41, 95%CI 1.17 to 1.68).<br /><b>Conclusions</b><br />In this large cohort study, we characterise the relationship between AR and PHT in adults. In patients with ≥moderate AR, PHT is associated with a progressive risk of mortality, even at mildly elevated levels.<br /><br />© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.<br /><br /><small>Heart: 03 Apr 2023; epub ahead of print</small></div>

<div><h4>Pacing induced cardiomyopathy: recognition and management.</h4><i>Ponnusamy SS, Syed T, Vijayaraman P</i><br /><AbstractText>Right ventricle (RV) apex continues to remain as the standard pacing site in the ventricle due to ease of implantation, procedural safety and lack of convincing evidence of better clinical outcomes from non-apical pacing sites. Electrical dyssynchrony resulting in abnormal ventricular activation and mechanical dyssynchrony resulting in abnormal ventricular contraction during RV pacing can result in adverse LV remodelling predisposing some patients for recurrent heart failure (HF) hospitalisation, atrial arrhythmias and increased mortality. While there are significant variations in the definition of pacing induced cardiomyopathy (PIC), combining both echocardiographic and clinical features, the most acceptable definition for PIC would be left ventricular ejection fraction (LVEF) of <50%, absolute decline of LVEF by ≥10% and/or new-onset HF symptoms or atrial fibrillation (AF) after pacemaker implantation. Based on the definitions used, the prevalence of PIC varies between 6% and 25% with overall pooled prevalence of 12%. While most patients undergoing RV pacing do not develop PIC, male sex, chronic kidney disease, previous myocardial infarction, pre-existing AF, baseline LVEF, native QRS duration, RV pacing burden, and paced QRS duration are the factors associated with increased risk for PIC. While conduction system pacing (CSP) using His bundle pacing and left bundle branch pacing appear to reduce the risk for PIC compared with RV pacing, both biventricular pacing and CSP may be used to effectively reverse PIC.</AbstractText><br /><br />© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.<br /><br /><small>Heart: 29 Mar 2023; epub ahead of print</small></div>

<div><h4>Prevalence and diagnostic significance of de-novo 12-lead ECG changes after COVID-19 infection in elite soccer players.</h4><i>Bhatia RT, Malhotra A, MacLachlan H, Gati S, ... Papadakis M, Sharma S</i><br /><b>Background:</b><br/>and aim</b><br />The efficacy of pre-COVID-19 and post-COVID-19 infection 12-lead ECGs for identifying athletes with myopericarditis has never been reported. We aimed to assess the prevalence and significance of de-novo ECG changes following COVID-19 infection.<br /><b>Methods</b><br />In this multicentre observational study, between March 2020 and May 2022, we evaluated consecutive athletes with COVID-19 infection. Athletes exhibiting de-novo ECG changes underwent cardiovascular magnetic resonance (CMR) scans. One club mandated CMR scans for all players (n=30) following COVID-19 infection, despite the absence of cardiac symptoms or de-novo ECG changes.<br /><b>Results</b><br />511 soccer players (median age 21 years, IQR 18-26 years) were included. 17 (3%) athletes demonstrated de-novo ECG changes, which included reduction in T-wave amplitude in the inferior and lateral leads (n=5), inferior leads (n=4) and lateral leads (n=4); inferior T-wave inversion (n=7); and ST-segment depression (n=2). 15 (88%) athletes with de-novo ECG changes revealed evidence of inflammatory cardiac sequelae. All 30 athletes who underwent a mandatory CMR scan had normal findings. Athletes revealing de-novo ECG changes had a higher prevalence of cardiac symptoms (71% vs 12%, p<0.0001) and longer median symptom duration (5 days, IQR 3-10) compared with athletes without de-novo ECG changes (2 days, IQR 1-3, p<0.001). Among athletes without cardiac symptoms, the additional yield of de-novo ECG changes to detect cardiac inflammation was 20%.<br /><b>Conclusions</b><br />3% of athletes demonstrated de-novo ECG changes post COVID-19 infection, of which 88% were diagnosed with cardiac inflammation. Most affected athletes exhibited cardiac symptoms; however, de-novo ECG changes contributed to a diagnosis of cardiac inflammation in 20% of athletes without cardiac symptoms.<br /><br />© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.<br /><br /><small>Heart: 27 Mar 2023; epub ahead of print</small></div>

<div><h4>Metabolic syndrome and ischaemic stroke in non-anticoagulated atrial fibrillation with low CHADS-VASc scores.</h4><i>Ahn HJ, Lee SR, Choi EK, Lee SW, ... Oh S, Lip GYH</i><br /><b>Objective</b><br />Conflicting results have been reported on whether metabolic syndrome (MetS) confers an increased risk of ischaemic stroke in atrial fibrillation (AF). We investigated the risk of ischaemic stroke according to MetS in patients with AF who are not indicated for oral anticoagulants.<br /><b>Methods</b><br />A total of 76 015 oral anticoagulant-naïve patients with AF with low Congestive Heart Failure, Hypertension, Age ≥75 years (Doubled), Diabetes Mellitus, Stroke (Doubled), Vascular Disease, Age 65-74 years, Sex Category (Female) (CHA<sub>2</sub>DS<sub>2</sub>-VASc) score (0 and 1) were included from the National Health Information Database. The risk of ischaemic stroke was evaluated according to MetS, the number of MetS components (metabolic burden), and individual metabolic components defined by health examination data within 2 years of AF diagnosis.<br /><b>Results</b><br />MetS was prevalent among 21 570 (28.4%) of the entire study population (mean age 49.8±11.1 years, mean CHA<sub>2</sub>DS<sub>2</sub>-VASc score 0.7±0.5). During a mean follow-up of 5.1 years, ischaemic stroke occurred in 1395 (1.84%) patients. MetS was associated with a higher risk of ischaemic stroke (adjusted HR (aHR) 1.19, 95% CI 1.06 to 1.33, p=0.002). Patients with the highest number of MetS components (4 or 5) showed the greatest aHR of 1.38 (95% CI 1.13 to 1.69), whereas those with a single component had a marginal risk of ischaemic stroke (aHR 1.17, 95% CI 0.97 to 1.40). Elevated blood pressure and increased waist circumference were independent components associated with 1.48-fold and 1.15-fold higher risks of ischaemic stroke, respectively.<br /><b>Conclusion</b><br />Among AF patients with CHA<sub>2</sub>DS<sub>2</sub>-VASc scores of 0 and 1 with no anticoagulation, MetS is associated with an increased risk of ischaemic stroke. Given the linear incremental association between metabolic burden and ischaemic stroke, the integrated management of metabolic derangements in AF is required.<br /><br />© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.<br /><br /><small>Heart: 24 Mar 2023; epub ahead of print</small></div>

<div><h4>Perioperative care differences of surgical aortic valve replacement between North America and Europe.</h4><i>Velders BJJ, Vriesendorp MD, De Lind Van Wijngaarden RAF, Rao V, ... Liu F, Klautz RJM</i><br /><b>Objective</b><br />To describe differences between North America and Europe in the perioperative management of patients undergoing surgical aortic valve replacement (SAVR).<br /><b>Methods</b><br />Patients with moderate or greater aortic stenosis or regurgitation requiring SAVR were enrolled in a prospective observational cohort evaluating the safety and efficacy of a new stented bioprosthesis at 25 centres in North America (Canada and the USA) and 13 centres in Europe (Germany, the Netherlands, France, the UK, Switzerland and Italy). While all patients underwent implantation with the same bioprosthetic model, perioperative management was left to the discretion of participating centres. Perioperative care was described in detail including outcomes up to 1-year follow-up.<br /><b>Results</b><br />Among 1118 patients, 643 (58%) were implanted in North America, and 475 (42%) were implanted in Europe. Patients in Europe were older, had a lower body mass index, less bicuspid disease and worse degree of aortic stenosis at baseline. In Europe, anticoagulant therapy at discharge was more aggressive, whereas length of stay was longer, and discharges directly to home were less common. Rehospitalisation risk was lower in Europe at 30 days (8.5% vs 15.9%) but converged at 1-year follow-up (26.5% vs 28.1%). Within continents, there were major differences between individual countries concerning perioperative management.<br /><b>Conclusion</b><br />Contemporary perioperative management of SAVR patients varies between North America and Europe in patient selection, procedural techniques, antithrombotic regimen and discharge management. Furthermore, rehospitalisation differed largely between continents and countries. Hence, geographical setting must be considered during design and interpretation of trials on SAVR.<br /><b>Trial registration number</b><br />NCT02088554.<br /><br />© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.<br /><br /><small>Heart: 24 Mar 2023; epub ahead of print</small></div>

<div><h4>Brady- and tachyarrhythmias detected by continuous rhythm monitoring in paroxysmal atrial fibrillation.</h4><i>Frausing MHJP, Van De Lande ME, Maass AH, Nguyen BO, ... Nielsen JC, Rienstra M</i><br /><b>Objective</b><br />Atrial fibrillation (AF) is associated with adverse events including conduction disturbances, ventricular arrhythmias and sudden death. The aim of this study was to examine brady- and tachyarrhythmias using continuous rhythm monitoring in patients with paroxysmal self-terminating AF (PAF).<br /><b>Methods</b><br />In this multicentre observational substudy to the Reappraisal of Atrial Fibrillation: interaction between hyperCoagulability, Electrical remodelling and Vascular destabilisation in the progression of AF (RACE V), we included 392 patients with PAF and at least 2 years of continuous rhythm monitoring. All patients received an implantable loop recorder, and all detected episodes of tachycardia ≥182 beats per minute (BPM), bradycardia ≤30 BPM or pauses ≥5 s were adjudicated by three physicians.<br /><b>Results</b><br />Over 1272 patient-years of continuous rhythm monitoring, we adjudicated 1940 episodes in 175 patients (45%): 106 (27%) patients experienced rapid AF or atrial flutter (AFL), pauses ≥5 s or bradycardias ≤30 BPM occurred in 47 (12%) patients and in 22 (6%) patients, we observed both episode types. No sustained ventricular tachycardias occurred. In the multivariable analysis, age >70 years (HR 2.3, 95% CI 1.4 to 3.9), longer PR interval (HR 1.9, 1.1-3.1), CHA<sub>2</sub>DS<sub>2</sub>-VASc score ≥2 (HR 2.2, 1.1-4.5) and treatment with verapamil or diltiazem (HR 0.4, 0.2-1.0) were significantly associated with bradyarrhythmia episodes. Age >70 years was associated with lower rates of tachyarrhythmias.<br /><b>Conclusions</b><br />In a cohort exclusive to patients with PAF, almost half experienced severe bradyarrhythmias or AF/AFL with rapid ventricular rates. Our data highlight a higher than anticipated bradyarrhythmia risk in PAF.<br /><b>Trial registration number</b><br />NCT02726698.<br /><br />© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.<br /><br /><small>Heart: 22 Mar 2023; epub ahead of print</small></div>

<div><h4>Haemodynamic and metabolic adaptations in coronary microvascular disease.</h4><i>Noaman S, Kaye DM, Nanayakkara S, Dart AM, ... Cox N, Chan W</i><br /><b>Objective</b><br />We aimed to evaluate the microcirculatory resistance (MR) and myocardial metabolic adaptations at rest and in response to increased cardiac workload in patients with suspected coronary microvascular dysfunction (CMD).<br /><b>Methods</b><br />Patients with objective ischaemia and/or myocardial injury and non-obstructive coronary artery disease underwent thermodilution-derived microcirculatory assessment and transcardiac blood sampling during graded exercise with adenosine-mediated hyperaemia. We measured MR at rest and following supine cycle ergometry. Patients (n=24) were stratified by the resting index of MR (IMR) into normal-IMR (IMR<22U, n=12) and high-IMR groups (IMR≥22U, n=12).<br /><b>Results</b><br />The mean age was 57 years; 67% were males and 38% had hypertension. The normal-IMR group had increased IMR response to exercise (16±5 vs 23±12U, p=0.03) compared with the high-IMR group, who had persistently elevated IMR at rest and following exercise (38±19 vs 33±15U, p=0.39) despite similar exercise duration and rate-pressure product between the groups, both p>0.05. The normal-IMR group had augmented oxygen extraction ratio following exercise (53±18 vs 64±11%, p=0.03) compared with the high-IMR group (65±14 vs 59±11%, p=0.26). The postexercise lactate uptake was greater in the high-IMR (0.04±0.05 vs 0.11±0.07 mmol/L, p=0.004) compared with normal-IMR group (0.08±0.06 vs 0.09±0.09 mmol/L, p=0.67). The high-IMR group demonstrated greater troponin release following exercise compared with the normal-IMR group (0.13±0.12 vs 0.001±0.05 ng/L, p=0.03).<br /><b>Conclusions</b><br />Patients with suspected CMD appear to have distinctive microcirculatory resistive and myocardial metabolic profiles at rest and in response to exercise. These differences in phenotypes may permit individualised therapies targeting microvascular responsiveness (normal-IMR group) and/or myocardial metabolic adaptations (normal-IMR and high-IMR groups).<br /><br />© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.<br /><br /><small>Heart: 17 Mar 2023; epub ahead of print</small></div>

<div><h4>One-year quality-of-life outcomes of cardiac arrest survivors by initial defibrillation provider.</h4><i>Haskins B, Nehme Z, Andrew E, Bernard S, Cameron P, Smith K</i><br /><b>Objective</b><br />To assess the long-term functional and health-related quality-of-life (HRQoL) outcomes for out-of-hospital cardiac arrest (OHCA) survivors stratified by initial defibrillation provider.<br /><b>Methods</b><br />This retrospective study included adult non-traumatic OHCA with initial shockable rhythms between 2010 and 2019. Survivors at 12 months after arrest were invited to participate in structured telephone interviews. Outcomes were identified using the Glasgow Outcome Scale-Extended (GOS-E), EuroQol-5 Dimension (EQ-5D), 12-Item Short Form Health Survey and living and work status-related questions.<br /><b>Results</b><br />6050 patients had initial shockable rhythms, 3211 (53.1%) had a pulse on hospital arrival, while 1879 (31.1%) were discharged alive. Bystander defibrillation using the closest automated external defibrillator had the highest survival rate (52.8%), followed by dispatched first responders (36.7%) and paramedics (27.9%). 1802 (29.8%) patients survived to 12-month postarrest; of these 1520 (84.4%) were interviewed. 1088 (71.6%) were initially shocked by paramedics, 271 (17.8%) by first responders and 161 (10.6%) by bystanders. Bystander-shocked survivors reported higher rates of living at home without care (87.5%, 75.2%, 77.0%, p<0.001), upper good recovery (GOS-E=8) (41.7%, 30.4%, 30.6%, p=0.002) and EQ-5D visual analogue scale (VAS) ≥80 (64.9%, 55.9%, 52.9%, p=0.003) compared with first responder and paramedics, respectively. After adjustment, initial bystander defibrillation was associated with higher odds of EQ-5D VAS ≥80 (adjusted OR (AOR) 1.56, 95% CI 1.15-2.10; p=0.004), good functional recovery (GOS-E ≥7) (AOR 1.53, 95% CI 1.12-2.11; p=0.009), living at home without care (AOR 1.77, 95% CI 1.16-2.71; p=0.009) and returning to work (AOR 1.72, 95% CI 1.05-2.81; p=0.031) compared with paramedic defibrillation.<br /><b>Conclusion</b><br />Survivors receiving initial bystander defibrillation reported better functional and HRQoL outcomes at 12 months after arrest compared with those initially defibrillated by paramedics.<br /><br />© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.<br /><br /><small>Heart: 16 Mar 2023; epub ahead of print</small></div>

<div><h4>Role of percutaneous coronary intervention in the modern-day management of chronic coronary syndrome.</h4><i>Cartlidge T, Kovacevic M, Navarese EP, Werner G, Kunadian V</i><br /><AbstractText>Contemporary randomised trials of percutaneous coronary intervention (PCI) in chronic coronary syndrome (CCS) demonstrate no difference between patients treated with a conservative or invasive strategy with respect to all-cause mortality or myocardial infarction, although trials lack power to test for individual endpoints and long-term follow-up data are needed. Open-label trials consistently show greater improvement in symptoms and quality of life among patients with stable angina treated with PCI. Further studies are awaited to clarify this finding. In patients with severe left ventricular (LV) systolic dysfunction and obstructive coronary artery disease in the Revascularization for Ischemic Ventricular Dysfunction trial, PCI has not been found to improve all-cause mortality, heart failure hospitalisation or recovery of LV function when compared with medical therapy. PCI was, however, performed without additional hazard and so remains a treatment option when there are favourable patient characteristics. The majority of patients reported no angina, and the low burden of angina in many of the randomised PCI trials is a widely cited limitation. Despite contentious evidence, elective PCI for CCS continues to play a significant role in UK clinical practice. While PCI for urgent indications has more than doubled since 2006, the rate of elective PCI remains unchanged. PCI remains an important strategy when symptoms are not well controlled, and we should maximise its value with appropriate patient selection. In this review, we provide a framework to assist in critical interpretation of findings from most recent trials and meta-analysis evidence.</AbstractText><br /><br />© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.<br /><br /><small>Heart: 16 Mar 2023; epub ahead of print</small></div>

<div><h4>Elective ascending aortic aneurysm repair outcomes in a nationwide US cohort.</h4><i>Beyer SE, Secemsky EA, Khabbaz K, Carroll BJ</i><br /><b>Objective</b><br />To quantify contemporary outcomes following elective ascending aortic aneurysm repair, to determine risk factors for adverse events and to evaluate difference by institutional surgical volume.<br /><b>Methods</b><br />We included all elective hospitalisations of adult patients with an ascending aortic aneurysm who underwent aneurysm repair in the Nationwide Readmissions Database between 2016 and 2019. The primary outcome was a composite of in-hospital mortality, stroke (ischaemic and non-ischaemic) and myocardial infarction (MI). We identified independent predictor of adverse events and investigated outcomes by institutional volume.<br /><b>Results</b><br />Among 12 043 patients (mean 62.8 years of age, 28.0% female), MI, stroke or in-hospital death occurred in 598 (4.9%) patients during the index admission (acute stroke: 2.7%, MI: 0.7%, in-hospital death: 2.0%). The strongest predictors of in-hospital death, stroke or MI were chronic weight loss, pulmonary circulation disorder and concomitant descending aortic surgery. Higher procedural volume was associated with a lower incidence of in-hospital death, stroke or MI (OR comparing the highest with the lowest tertile 0.71, 95% CI 0.57 to 0.87; p=0.001) and in-hospital death (OR 0.51, 95% CI 0.37 to 0.72; p<0.001), but no difference in 30-day readmissions.<br /><b>Conclusions</b><br />The overall rate of in-hospital death, stroke and MI is nearly 5% in patients undergoing elective ascending aortic aneurysm repair. Among several predictors, chronic weight loss is associated with the largest increase in the risk of poor outcomes. Higher hospital volume is associated with a lower in-hospital mortality, highlighting the importance to refer patients to high-volume centres while discussing the risks and benefits of proceeding with repair.<br /><br />© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.<br /><br /><small>Heart: 16 Mar 2023; epub ahead of print</small></div>

<div><h4>Primary prevention of cardiovascular disease in women with a Mediterranean diet: systematic review and meta-analysis.</h4><i>Pant A, Gribbin S, McIntyre D, Trivedi R, ... Chow CK, Zaman S</i><br /><b>Background</b><br />Dietary modification is a cornerstone of cardiovascular disease (CVD) prevention. A Mediterranean diet has been associated with a lower risk of CVD but no systematic reviews have evaluated this relationship specifically in women.<br /><b>Objective</b><br />To determine the association between higher versus lower adherence to a Mediterranean diet and incident CVD and total mortality in women.<br /><b>Methods</b><br />A systematic search of Medline, Embase, CINAHL, Scopus, and Web of Science (2003-21) was performed. Randomised controlled trials and prospective cohort studies with participants without previous CVD were included. Studies were eligible if they reported a Mediterranean diet score and comprised either all female participants or stratified outcomes by sex. The primary outcome was CVD and/or total mortality. A random effects meta-analysis was conducted to calculate pooled hazard ratios (HRs) and confidence intervals (CIs).<br /><b>Results</b><br />Sixteen prospective cohort studies were included in the meta-analysis (n=7 22 495 female participants). In women, higher adherence to a Mediterranean diet was associated with a lower CVD incidence (HR 0.76, 95% CI 0.72 to 0.81; I<sup>2</sup>=39%, p test for heterogeneity=0.07), total mortality (HR 0.77, 95% CI 0.74 to 0.80; I<sup>2</sup>=21%, p test for heterogeneity=0.28), and coronary heart disease (HR 0.75, 95% CI 0.65 to 0.87; I<sup>2</sup>=21%, p test for heterogeneity=0.28). Stroke incidence was lower in women with higher Mediterranean diet adherence (HR 0.87, 95% CI 0.76 to 1.01; I<sup>2</sup>=0%, p test for heterogeneity=0.89), but this result was not statistically significant.<br /><b>Conclusion</b><br />This study supports a beneficial effect of the Mediterranean diet on primary prevention of CVD and death in women, and is an important step in enabling sex specific guidelines.<br /><br />© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.<br /><br /><small>Heart: 14 Mar 2023; epub ahead of print</small></div>

<div><h4>Left atrial phasic function: physiology, clinical assessment and prognostic value.</h4><i>Ferkh A, Clark A, Thomas L</i><br /><AbstractText>Left atrial (LA) phasic function provides significant insights into the pathophysiology of cardiovascular disease. LA function is described in three phases: reservoir (atrial filling, during systole), conduit (passive emptying, during early diastole) and contractile (active emptying, during late diastole). LA phasic function can be evaluated by different imaging modalities, and a variety of techniques including volumetric analysis, deformation (strain) and Doppler methods. LA phasic function (particularly LA reservoir strain) is more sensitive and provides earlier detection of LA dysfunction than alterations in LA volume. LA function parameters have also demonstrated significant diagnostic and prognostic value, particularly in heart failure, atrial fibrillation and stroke. However, there remain barriers to implementation of phasic function parameters in clinical practice and guidelines. This review outlines the physiology of LA phasic function, methods of assessment, and its diagnostic and prognostic utility in varying pathologies.</AbstractText><br /><br />© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.<br /><br /><small>Heart: 14 Mar 2023; epub ahead of print</small></div>

<div><h4>Role of computed tomography cardiac angiography in acute chest pain syndromes.</h4><i>Greer C, Williams MC, Newby DE, Adamson PD</i><br /><AbstractText>Use of CT coronary angiography (CTCA) to evaluate chest pain has rapidly increased over the recent years. While its utility in the diagnosis of coronary artery disease in stable chest pain syndromes is clear and is strongly endorsed by international guidelines, the role of CTCA in the acute setting is less certain. In the low-risk setting, CTCA has been shown to be accurate, safe and efficient but inherent low rates of adverse events in this population and the advent of high-sensitivity troponin testing have left little room for CTCA to show any short-term clinical benefit.In higher-risk populations, CTCA has potential to fulfil a gatekeeper role to invasive angiography. The high negative predictive value of CTCA is maintained while also identifying non-obstructive coronary disease and alternative diagnoses in the substantial group of patients presenting with chest pain who do not have type 1 myocardial infarction. For those with obstructive coronary disease, CTCA provides accurate assessment of stenosis severity, characterisation of high-risk plaque and findings associated with perivascular inflammation. This may allow more appropriate selection of patients to proceed to invasive management with no disadvantage in outcomes and can provide a more comprehensive risk stratification to guide both acute and long-term management than routine invasive angiography.</AbstractText><br /><br />© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.<br /><br /><small>Heart: 13 Mar 2023; epub ahead of print</small></div>

<div><h4>Sex-specific trajectories of molecular cardiometabolic traits from childhood to young adulthood.</h4><i>O\'Keeffe LM, Tilling K, Bell JA, Walsh PT, ... Davey Smith G, Kearney PM</i><br /><b>Background</b><br />The changes which typically occur in molecular causal risk factors and predictive biomarkers for cardiometabolic diseases across early life are not well characterised.<br /><b>Methods</b><br />We quantified sex-specific trajectories of 148 metabolic trait concentrations including various lipoprotein subclasses from age 7 years to 25 years. Data were from 7065 to 7626 offspring (11 702 to14 797 repeated measures) of the Avon Longitudinal Study of Parents and Children birth cohort study. Outcomes were quantified using nuclear magnetic resonance spectroscopy at 7, 15, 18 and 25 years. Sex-specific trajectories of each trait were modelled using linear spline multilevel models.<br /><b>Results</b><br />Females had higher very-low-density lipoprotein (VLDL) particle concentrations at 7 years. VLDL particle concentrations decreased from 7 years to 25 years with larger decreases in females, leading to lower VLDL particle concentrations at 25 years in females. For example, females had a 0.25 SD (95% CI 0.20 to 0.31) higher small VLDL particle concentration at 7 years; mean levels decreased by 0.06 SDs (95% CI -0.01 to 0.13) in males and 0.85 SDs (95% CI 0.79 to 0.90) in females from 7 years to 25 years, leading to 0.42 SDs (95% CI 0.35 to 0.48) lower small VLDL particle concentrations in females at 25 years. Females had lower high-density lipoprotein (HDL) particle concentrations at 7 years. HDL particle concentrations increased from 7 years to 25 years with larger increases among females leading to higher HDL particle concentrations in females at 25 years.<br /><b>Conclusion</b><br />Childhood and adolescence are important periods for the emergence of sex differences in atherogenic lipids and predictive biomarkers for cardiometabolic disease, mostly to the detriment of males.<br /><br />© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY. Published by BMJ.<br /><br /><small>Heart: 13 Mar 2023; epub ahead of print</small></div>

<div><h4>Prognostic models for heart failure in patients with type 2 diabetes: a systematic review and meta-analysis.</h4><i>Kostopoulos G, Doundoulakis I, Toulis KA, Karagiannis T, Tsapas A, Haidich AB</i><br /><b>Objective</b><br />To provide a systematic review, critical appraisal, assessment of performance and generalisability of all the reported prognostic models for heart failure (HF) in patients with type 2 diabetes (T2D).<br /><b>Methods</b><br />We performed a literature search in Medline, Embase, Central Register of Controlled Trials, Cochrane Database of Systematic Reviews and Scopus (from inception to July 2022) and grey literature to identify any study developing and/or validating models predicting HF applicable to patients with T2D. We extracted data on study characteristics, modelling methods and measures of performance, and we performed a random-effects meta-analysis to pool discrimination in models with multiple validation studies. We also performed a descriptive synthesis of calibration and we assessed the risk of bias and certainty of evidence (high, moderate, low).<br /><b>Results</b><br />Fifty-five studies reporting on 58 models were identified: (1) models developed in patients with T2D for HF prediction (n=43), (2) models predicting HF developed in non-diabetic cohorts and externally validated in patients with T2D (n=3), and (3) models originally predicting a different outcome and externally validated for HF (n=12). RECODe (C-statistic=0.75 95% CI (0.72, 0.78), 95% prediction interval (PI) (0.68, 0.81); high certainty), TRS-HFDM (C-statistic=0.75 95% CI (0.69, 0.81), 95% PI (0.58, 0.87); low certainty) and WATCH-DM (C-statistic=0.70 95% CI (0.67, 0.73), 95% PI (0.63, 0.76); moderate certainty) showed the best performance. QDiabetes-HF demonstrated also good discrimination but was externally validated only once and not meta-analysed.<br /><b>Conclusions</b><br />Among the prognostic models identified, four models showed promising performance and, thus, could be implemented in current clinical practice.<br /><br />© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.<br /><br /><small>Heart: 10 Mar 2023; epub ahead of print</small></div>

<div><h4>Expert consensus recommendations for the provision of infective endocarditis services: updated guidance from the Joint British Societies.</h4><i>Sandoe JAT, Ahmed F, Arumugam P, Guleri A, ... Wendler O, Chambers JB</i><br /><AbstractText>Infective endocarditis (IE) remains a difficult condition to diagnose and treat and is an infection of high consequence for patients, causing long hospital stays, life-changing complications and high mortality. A new multidisciplinary, multiprofessional, British Society for Antimicrobial Chemotherapy (BSAC)-ledWorking Party was convened to undertake a focused systematical review of the literature and to update the previous BSAC guidelines relating delivery of services for patients with IE. A scoping exercise identified new questions concerning optimal delivery of care, and the systematic review identified 16 231 papers of which 20 met the inclusion criteria. Recommendations relating to endocarditis teams, infrastructure and support, endocarditis referral processes, patient follow-up and patient information, and governance are made as well as research recommendations. This is a report of a joint Working Party of the BSAC, British Cardiovascular Society, British Heart Valve Society, British Society of Echocardiography, Society of Cardiothoracic Surgeons of Great Britain and Ireland, British Congenital Cardiac Association and British Infection Association.</AbstractText><br /><br />© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.<br /><br /><small>Heart: 10 Mar 2023; epub ahead of print</small></div>

<div><h4>Holistic approach to drug therapy in a patient with heart failure.</h4><i>Forsyth P, Beezer J, Bateman J</i><br /><AbstractText>Heart failure (HF) is a growing global public health problem affecting at least 26 million people worldwide. The evidence-based landscape for HF treatment has changed at a rapid rate over the last 30 years. International guidelines for the management of HF now recommend the use of four pillars in all patients with reduced ejection fraction: angiotensin receptor neprilysin inhibitors or ACE inhibitors, beta blockers, mineralocorticoid receptor antagonists and sodium-glucose co-transporter-2 inhibitors. Beyond the main four pillar therapies, numerous further pharmacological treatments are also available in specific patient subtypes. These armouries of drug therapy are impressive, but where does this leave us with individualised and patient-centred care? This paper reviews the common considerations needed to provide a holistic, tailored and individual approach to drug therapy in a patient with HF with reduced ejection fraction, including shared decision making, initiating and sequencing of HF pharmacotherapy, drug-related considerations, polypharmacy and adherence.</AbstractText><br /><br />© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.<br /><br /><small>Heart: 10 Mar 2023; epub ahead of print</small></div>

<div><h4>Sex difference in atrial fibrillation recurrence after catheter ablation and antiarrhythmic drugs.</h4><i>Park YJ, Park JW, Yu HT, Kim TH, ... Lee MH, Pak HN</i><br /><b>Objective</b><br />The risk of recurrence after atrial fibrillation (AF) catheter ablation (AFCA) is higher in women than in men. However, it is unknown whether a sex difference exists in antiarrhythmic drug (AAD) responsiveness among patients with recurrence.<br /><b>Methods</b><br />Among 2999 consecutive patients (26.5% women, 58.3±10.9 years old, 68.1% paroxysmal AF) who underwent de novo AFCA, we compared and evaluated the sex differences in rhythm outcome in 1094 patients with recurrence and in 788 patients who subsequently underwent rhythm control with AAD.<br /><b>Results</b><br />During a follow-up of 48.2±34.9 months, 1094 patients (36.5%) had AF recurrence after AFCA, and 508 of 788 patients (64.5%) had AF recurrence under AAD. Although the rhythm outcome of a de novo AFCA was worse (log-rank p=0.041, HR 1.28, 95% CI 1.02 to 1.59), p=0.031) in women, AAD response after postprocedural recurrences was better in women than in men (log-rank p=0.003, HR 0.75, 95% CI 0.59 to 0.95, p=0.022), especially in women older than 60 years old (log-rank p=0.003). In 249 patients who underwent repeat procedure after AAD use, the pulmonary vein (PV) reconnection rate (62.7% vs 76.8%, p=0.048) was lower in women than in men but not the existence of extra-PV trigger (37.8% vs 25.4%, p=0.169).<br /><b>Conclusions</b><br />Although women showed worse rhythm outcomes than men after AFCA, the post-AFCA AAD response was better in elderly women than in men.<br /><b>Trial registration number</b><br />NCT02138695.<br /><br />© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.<br /><br /><small>Heart: 10 Mar 2023; 109:519-526</small></div>

<div><h4>Evolution and triggers of defibrillator shocks in patients with arrhythmogenic right ventricular cardiomyopathy.</h4><i>Molitor N, Hofer D, Çimen T, Gasperetti A, ... Duru F, Saguner AM</i><br /><b>Introduction</b><br />Implantable cardioverter-defibrillators (ICDs) can prevent sudden cardiac death due to ventricular arrhythmias in patients with arrhythmogenic right ventricular cardiomyopathy (ARVC). The aim of our study was to assess the cumulative burden, evolution and potential triggers of appropriate ICD shocks during long-term follow-up, which may help to reduce and further refine individual arrhythmic risk in this challenging disease.<br /><b>Methods</b><br />This retrospective cohort study included 53 patients with definite ARVC according to the 2010 Task Force Criteria from the multicentre Swiss ARVC Registry with an implanted ICD for primary or secondary prevention. Follow-up was conducted by assessing all available patient records from patient visits, hospitalisations, blood samples, genetic analysis, as well as device interrogation and tracings.<br /><b>Results</b><br />Fifty-three patients (male 71.7%, mean age 43±2.2 years, genotype positive 58.5%) were analysed during a median follow-up of 7.9 (IQR 10) years. In 29 (54.7%) patients, 177 appropriate ICD shocks associated with 71 shock episodes occurred. Median time to first appropriate ICD shock was 2.8 (IQR 3.6) years. Long-term risk of shocks remained high throughout long-term follow-up. Shock episodes occurred mainly during daytime (91.5%, n=65) and without seasonal preference. We identified potentially reversible triggers in 56 of 71 (78.9%) appropriate shock episodes, the main triggers representing physical activity, inflammation and hypokalaemia.<br /><b>Conclusion</b><br />The long-term risk of appropriate ICD shocks in patients with ARVC remains high during long-term follow-up. Ventricular arrhythmias occur more often during daytime, without seasonal preference. Reversible triggers are frequent with the most common triggers for appropriate ICD shocks being physical activity, inflammation and hypokalaemia in this patient population.<br /><br />© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.<br /><br /><small>Heart: 08 Mar 2023; epub ahead of print</small></div>

<div><h4>Effect of opioids for breathlessness in heart failure: a systematic review and meta-analysis.</h4><i>Gaertner J, Fusi-Schmidhauser T, Stock S, Siemens W, Vennedey V</i><br /><b>Background</b><br />For the treatment of breathlessness in heart failure (HF), most textbooks advocate the use of opioids. Yet, meta-analyses are lacking.<br /><b>Methods</b><br />A systematic review was performed for randomised controlled trials (RCTs) assessing effects of opioids on breathlessness (primary outcome) in patients with HF. Key secondary outcomes were quality of life (QoL), mortality and adverse effects. Cochrane Central Register of Controlled Trials, MEDLINE and Embase were searched in July 2021. Risk of bias (RoB) and certainty of evidence were assessed by the Cochrane RoB 2 Tool and Grading of Recommendations Assessment, Development and Evaluation criteria, respectively. The random-effects model was used as primary analysis in all meta-analyses.<br /><b>Results</b><br />After removal of duplicates, 1180 records were screened. We identified eight RCTs with 271 randomised patients. Seven RCTs could be included in the meta-analysis for the primary endpoint breathlessness with a standardised mean difference of 0.03 (95% CI -0.21 to 0.28). No study found statistically significant differences between the intervention and placebo. Several key secondary outcomes favoured placebo: risk ratio of 3.13 (95% CI 0.70 to 14.07) for nausea, 4.29 (95% CI 1.15 to 16.01) for vomiting, 4.77 (95% CI 1.98 to 11.53) for constipation and 4.42 (95% CI 0.79 to 24.87) for study withdrawal. All meta-analyses revealed low heterogeneity (I<sup>2</sup> in all these meta-analyses was <8%).<br /><b>Conclusion</b><br />Opioids for treating breathlessness in HF are questionable and may only be the very last option if other options have failed or in case of an emergency.<br /><b>Prospero registration number</b><br />CRD42021252201.<br /><br />© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.<br /><br /><small>Heart: 06 Mar 2023; epub ahead of print</small></div>

<div><h4>Likelihood reclassification by an acoustic-based score in suspected coronary artery disease.</h4><i>Rasmussen LD, Winther S, Karim SR, Westra J, ... Schmidt SE, Bøttcher M</i><br /><b>Objective</b><br />Validation studies of the 2019 European Society of Cardiology pretest probability model (ESC-PTP) for coronary artery disease (CAD) report that 35%-40% of patients have low pretest probability (ESC-PTP 5% to <15%). Acoustic detection of coronary stenoses could potentially improve clinical likelihood stratification. <br /><b>Aims:</b><br/>were to (1) investigate the diagnostic performance of an acoustic-based CAD score and (2) study the reclassification potential of a dual likelihood strategy by the ESC-PTP and a CAD score.<br /><b>Methods</b><br />Consecutive patients (n=1683) with stable angina symptoms referred for coronary CT angiography (CTA) underwent heart sound analyses by an acoustic CAD-score device. All patients with ≥50% luminal stenosis in any coronary segment at coronary CTA were referred to investigation with invasive coronary angiography (ICA) with fractional flow reserve (FFR).A predefined CAD-score cut-off ≤20 was used to rule out obstructive CAD.<br /><b>Results</b><br />In total, 439 patients (26%) had ≥50% luminal stenosis on coronary CTA. The subsequent ICA with FFR showed obstructive CAD in 199 patients (11.8%). Using the ≤20 CAD-score cut-off for obstructive CAD rule-out, sensitivity was 85.4% (95% CI 79.7 to 90.0), specificity 40.4% (95% CI 37.9 to 42.9), positive predictive value 16.1% (95% CI 13.9 to 18.5) and negative predictive value 95.4% (95% CI 93.4 to 96.9) in all patients. Applying the cut-off in ESC-PTP 5% to <15% patients, 316 patients (48%) were down-classified to very-low likelihood. The obstructive CAD prevalence was 3.5% in this group.<br /><b>Conclusion</b><br />In a large contemporary cohort of patients with low CAD likelihood, the additional use of an acoustic rule-out device showed a clear potential to downgrade likelihood and could supplement current strategies for likelihood assessment to avoid unnecessary testing.<br /><b>Trial registration number</b><br />NCT03481712.<br /><br />© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.<br /><br /><small>Heart: 06 Mar 2023; epub ahead of print</small></div>

<div><h4>Comparative effect of varenicline and nicotine patches on preventing repeat cardiovascular events.</h4><i>Robijn AL, Filion KB, Woodward M, Hsu B, ... Falster MO, Havard A</i><br /><b>Objective</b><br />To determine the comparative effectiveness of postdischarge use of varenicline versus prescription nicotine replacement therapy (NRT) patches for the prevention of recurrent cardiovascular events and mortality and whether this association differs by sex.<br /><b>Methods</b><br />Our cohort study used routinely collected hospital, pharmaceutical dispensing and mortality data for residents of New South Wales, Australia. We included patients hospitalised for a major cardiovascular event or procedure 2011-2017, who were dispensed varenicline or prescription NRT patches within 90day postdischarge. Exposure was defined using an approach analogous to intention to treat. Using inverse probability of treatment weighting with propensity scores to account for confounding, we estimated adjusted HRs for major cardiovascular events (MACEs), overall and by sex. We fitted an additional model with a sex-treatment interaction term to determine if treatment effects differed between males and females.<br /><b>Results</b><br />Our cohort of 844 varenicline users (72% male, 75% <65 years) and 2446 prescription NRT patch users (67% male, 65% <65 years) were followed for a median of 2.93 years and 2.34 years, respectively. After weighting, there was no difference in risk of MACE for varenicline relative to prescription NRT patches (aHR 0.99, 95% CI 0.82 to 1.19). We found no difference (interaction p=0.098) between males (aHR 0.92, 95% CI 0.73 to 1.16) and females (aHR 1.30, 95% CI 0.92 to 1.84), although the effect among females deviated from the null.<br /><b>Conclusion</b><br />We found no difference between varenicline and prescription NRT patches in the risk of recurrent MACE. These results should be considered when determining the most appropriate choice of smoking cessation pharmacotherapy.<br /><br />© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.<br /><br /><small>Heart: 06 Mar 2023; epub ahead of print</small></div>