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Kirstine Lærum Sibilitz, Lizette Anayo, Rod S Taylor
Published: 19 October 2021
by BMJ
Abstract:
The changing disease pattern and expected increase in healthcare burden, and the large number of acute hospitalisations after valve surgery require a well‐established after‐care including cardiac rehabilitation. Issues after valve surgery also include physical and psychological issues. Physical inactivity is a problem for heart valve surgery patients, who may experience presurgical dyspnoea and physical incapacity, immobilisation during hospitalisation, and potential postsurgical complications and restrictions due to healing of the sternum. Open heart surgery is a stressful life event and health-related quality of life (HRQoL) is likely to be negatively affected, along with mental health; patients may require support for depressive symptoms and anxiety. Although such problems may also occur after percutaneous procedures, recent studies suggest that after transcatheter aortic valve replacement (TAVR), patients have much better HRQoL within 2 weeks of the procedure.
E Madelief J Marsman, Pieter G Postema,
Published: 14 October 2021
by BMJ
Abstract:
Brugada syndrome (BrS) is an inherited cardiac disorder, characterised by a typical ECG pattern and an increased risk of arrhythmias and sudden cardiac death (SCD). BrS is a challenging entity, in regard to diagnosis as well as arrhythmia risk prediction and management. Nowadays, asymptomatic patients represent the majority of newly diagnosed patients with BrS, and its incidence is expected to rise due to (genetic) family screening. Progress in our understanding of the genetic and molecular pathophysiology is limited by the absence of a true gold standard, with consensus on its clinical definition changing over time. Nevertheless, novel insights continue to arise from detailed and in-depth studies, including the complex genetic and molecular basis. This includes the increasingly recognised relevance of an underlying structural substrate. Risk stratification in patients with BrS remains challenging, particularly in those who are asymptomatic, but recent studies have demonstrated the potential usefulness of risk scores to identify patients at high risk of arrhythmia and SCD. Development and validation of a model that incorporates clinical and genetic factors, comorbidities, age and gender, and environmental aspects may facilitate improved prediction of disease expressivity and arrhythmia/SCD risk, and potentially guide patient management and therapy. This review provides an update of the diagnosis, pathophysiology and management of BrS, and discusses its future perspectives.
, Emma Powell, Kevin Wing, Angel Yun Wong, , Charlotte Warren-Gash
Published: 13 October 2021
by BMJ
Abstract:
Objective The aim of this study was to investigate the association between oral anticoagulant type (direct oral anticoagulants (DOACs) vs vitamin K antagonists (VKAs)) and incident dementia or mild cognitive impairment (MCI) among patients with newly diagnosed atrial fibrillation (AF). Methods Using linked electronic health record (EHR) data from the Clinical Practice Research Datalink in the UK, we conducted a historical cohort study among first-time oral anticoagulant users with incident non-valvular AF diagnosed from 2012 to 2018. We compared the incidence of (1) clinically coded dementia and (2) MCI between patients prescribed VKAs and DOACs using Cox proportional hazards regression models, with age as the underlying timescale, accounting for calendar time and time on treatment, sociodemographic and lifestyle factors, clinical comorbidities and medications. Results Of 39 200 first-time oral anticoagulant users (44.6% female, median age 76 years, IQR 68–83), 20 687 (53%) were prescribed a VKA and 18 513 (47%) a DOAC at baseline. Overall, 1258 patients (3.2%) had GP-recorded incident dementia, incidence rate 16.5 per 1000 person-years. DOAC treatment for AF was associated with a 16% reduction in dementia diagnosis compared with VKA treatment in the whole cohort (adjusted HR 0.84, 95% CI: 0.73 to 0.98) and with a 26% reduction in incident MCI (adjusted HR 0.74, 95% CI: 0.65 to 0.84). Findings were similar across various sensitivity analyses. Conclusions Incident EHR-recorded dementia and MCI were less common among patients prescribed DOACs for new AF compared with those prescribed VKAs.
, , Diana Barreira, Antonio Rodríguez-Miguel, Encarnación Fernández-Antón, Miguel Gil, Alberto García-Lledó
Published: 13 October 2021
by BMJ
Abstract:
Objective To assess the relationship between influenza vaccination and risk of a first acute myocardial infarction (AMI) in the general population by different epidemic periods. Methods This is a population-based case–control study carried out in BIFAP (Base de datos para la investigación farmacoepidemiológica en atención primaria), over 2001–2015, in patients aged 40–99 years. Per each incident AMI case, five controls were randomly selected, individually matched for exact age, sex and index date (AMI diagnosis). A patient was considered vaccinated when he/she had a recorded influenza vaccination at least 14 days before the index date within the same season. The association between influenza vaccination and AMI risk was assessed through a conditional logistic regression, computing adjusted ORs (AOR) and their respective 95% CIs. The analysis was performed overall and by each of the three time epidemic periods per study year (pre-epidemic, epidemic and postepidemic). Results We identified 24 155 AMI cases and 120 775 matched controls. Of them, 31.4% and 31.2%, respectively, were vaccinated, yielding an AOR of 0.85 (95% CI 0.82 to 0.88). No effect modification by sex, age and background cardiovascular risk was observed. The reduced risk of AMI was observed shortly after vaccination and persisted over time. Similar results were obtained during the pre-epidemic (AOR=0.87; 95% CI 0.79 to 0.95), epidemic (AOR=0.89; 95% CI 0.82 to 0.96) and postepidemic (AOR=0.83; 95% CI 0.79 to 0.87) periods. No association was found with pneumococcal vaccine (AOR=1.10; 95% CI 1.06 to 1.15). Conclusions Results are compatible with a moderate protective effect of influenza vaccine on AMI in the general population, mostly in primary prevention, although bias due to unmeasured confounders may partly account for the results.
, , María Tamargo, , Tomas Datino, Angel Arenal, , Nina Soto, ,
Published: 11 October 2021
by BMJ
Abstract:
Objective The role of age in clinical characteristics and catheter ablation outcomes of atrioventricular nodal re-entrant tachycardia (AVNRT) or orthodromic atrioventricular re-entrant tachycardia (AVRT) has been assessed in retrospective studies categorising age by arbitrary cut-offs, but contemporary analyses of age-related trends are lacking. We aimed to study the relationship of age with epidemiological, clinical features and catheter ablation outcomes of AVNRT and AVRT. Methods We recruited 600 patients (median age 56 years, 60% female) with a confirmed diagnosis of AVNRT (n=455) or AVRT (n=145) by means of an electrophysiological study. They were interrogated for arrhythmia-related symptoms with a structured questionnaire and followed up to 1 year. We analysed age as a continuous variable using regression models and adjusting for relevant covariables. Results Both typical and atypical forms of AVNRT upraised with age while AVRT decreased (p<0.001 by regression). Female sex predominance in AVNRT was not observed in older patients. Overall, these tachycardias became more symptomatic with ageing despite a longer tachycardia cycle length (p<0.001) and regardless of the presence of structural heart disease, with a higher proportion of dizziness, syncope, chest pain or dyspnoea (p<0.005 for all) and a lower presence of palpitations or neck pounding (p0.05 for all). Conclusions Age, evaluated as a continuous variable, had a significant association with the clinical profile of patients with AVNRT and AVRT. Nevertheless, catheter ablation outcomes and complications were not significantly related to patients’ age.
W M Monique Verschuren, Jolanda M A Boer, Elisabeth H M Temme
Published: 11 October 2021
by BMJ
Patrick M Hyland, Jiaman Xu, Changyu Shen, Lawrence J Markson, Warren J Manning,
Published: 6 October 2021
by BMJ
Abstract:
Objective To identify potential race, sex and age disparities in performance of transthoracic echocardiography (TTE) over several decades. Methods TTE reports from five academic and community sites within a single integrated healthcare system were linked to 100% Medicare fee-for-service claims from 1 January 2005 to 31 December 2017. Multivariable Poisson regression was used to estimate adjusted rates of TTE utilisation after the index TTE according to baseline age, sex, race and comorbidities among individuals with ≥2 TTEs. Non-white race was defined as black, Asian, North American Native, Hispanic or other categories using Medicare-assigned race categories. Results A total of 15 870 individuals (50.1% female, mean 72.2±12.7 years) underwent a total of 63 535 TTEs (range 2–55/person) over a median (IQR) follow-up time of 4.9 (2.4–8.5) years. After the index TTE, the median TTE use was 0.72 TTEs/person/year (IQR 0.43–1.33; range 0.12–26.76). TTE use was lower in older individuals (relative risk (RR) for 10-year increase in age, 0.91, 95% CI 0.89 to 0.92, p<0.001), women (RR 0.97, 95% CI 0.95 to 0.99, p<0.001) and non-white individuals (RR 0.95, 95% CI 0.93 to 0.97, p<0.001). Black women in particular had the lowest relative use of TTE (RR 0.92, 95% CI 0.88 to 0.95, p<0.001). The only clinical conditions associated with increased TTE use after multivariable adjustment were heart failure (RR 1.04, 95% CI 1.00 to 1.08, p=0.04) and chronic obstructive pulmonary disease (RR 1.05, 95% CI 1.00 to 1.10, p=0.04). Conclusions Among Medicare beneficiaries with multiple TTEs in a single large healthcare system, the median TTE use after the index TTE was 0.72 TTEs/person/year, although this varied widely. Adjusted for comorbidities, female sex, non-white race and advancing age were associated with decreased TTE utilisation.
, Thomas A Kite, , , Lucy Kershaw, Andrew Baker, Helen Jordan, Gaurav Singh Gulsin, , Edwin J R van Beek, et al.
Published: 6 October 2021
by BMJ
Abstract:
Objectives To determine the contribution of comorbidities on the reported widespread myocardial abnormalities in patients with recent COVID-19. Methods In a prospective two-centre observational study, patients hospitalised with confirmed COVID-19 underwent gadolinium and manganese-enhanced MRI and CT coronary angiography (CTCA). They were compared with healthy and comorbidity-matched volunteers after blinded analysis. Results In 52 patients (median age: 54 (IQR 51–57) years, 39 males) who recovered from COVID-19, one-third (n=15, 29%) were admitted to intensive care and a fifth (n=11, 21%) were ventilated. Twenty-three patients underwent CTCA, with one-third having underlying coronary artery disease (n=8, 35%). Compared with younger healthy volunteers (n=10), patients demonstrated reduced left (ejection fraction (EF): 57.4±11.1 (95% CI 54.0 to 60.1) versus 66.3±5 (95 CI 62.4 to 69.8)%; p=0.02) and right (EF: 51.7±9.1 (95% CI 53.9 to 60.1) vs 60.5±4.9 (95% CI 57.1 to 63.2)%; p≤0.0001) ventricular systolic function with elevated native T1 values (1225±46 (95% CI 1205 to 1240) vs 1197±30 (95% CI 1178 to 1216) ms;p=0.04) and extracellular volume fraction (ECV) (31±4 (95% CI 29.6 to 32.1) vs 24±3 (95% CI 22.4 to 26.4)%; p<0.0003) but reduced myocardial manganese uptake (6.9±0.9 (95% CI 6.5 to 7.3) vs 7.9±1.2 (95% CI 7.4 to 8.5) mL/100 g/min; p=0.01). Compared with comorbidity-matched volunteers (n=26), patients had preserved left ventricular function but reduced right ventricular systolic function (EF: 51.7±9.1 (95% CI 53.9 to 60.1) vs 59.3±4.9 (95% CI 51.0 to 66.5)%; p=0.0005) with comparable native T1 values (1225±46 (95% CI 1205 to 1240) vs 1227±51 (95% CI 1208 to 1246) ms; p=0.99), ECV (31±4 (95% CI 29.6 to 32.1) vs 29±5 (95% CI 27.0 to 31.2)%; p=0.35), presence of late gadolinium enhancement and manganese uptake. These findings remained irrespective of COVID-19 disease severity, presence of myocardial injury or ongoing symptoms. Conclusions Patients demonstrate right but not left ventricular dysfunction. Previous reports of left ventricular myocardial abnormalities following COVID-19 may reflect pre-existing comorbidities. Trial registration number NCT04625075.
, Yunjiao Wang, Wanqin Zhang, Hongcai Shang
Published: 5 October 2021
by BMJ
Abstract:
Heart failure (HF) is a clinical syndrome in the late stage of cardiovascular disease and is associated with high prevalence, mortality and rehospitalisation rate. The pathophysiological mechanisms of HF have experienced the initial ‘water-sodium retention’ mode to ‘abnormal hemodynamics’ mode, and subsequent to ‘abnormal activation of neuroendocrine’ mode, which has extensively promoted the reform of HF treatment and updated the treatment concept. Since the Human Microbiome Project commencement, the study on intestinal microecology has swiftly developed, providing a new direction to reveal the occurrence of diseases and the mechanisms behind drug effects. Intestinal microecology comprises the gastrointestinal lumen, epithelial secretion, food entering the intestine, intestinal flora and metabolites. Choline and L-carnitine in the diet are metabolised to trimethylamine (TMA) by the intestinal micro-organisms, with TMA being absorbed into the blood. TMA then enters the liver through the portal vein circulation and is oxidised to trimethylamine oxide (TMAO) by the hepatic flavin-containing mono-oxygenase (FMO) family, especially FMO3. The circulating TMAO levels are associated with adverse outcomes in HF (mortality and readmission), and lower TMAO levels indicate better prognosis. As HF progresses, the concentration of TMAO in patients gradually increases. Whether the circulating TMAO level can be decreased by intervening with the intestinal microflora or relevant enzymes, thereby affecting the prognosis of patients with HF, has become a research hotspot. Therefore, based on the HF intestinal hypothesis, exploring the treatment strategy for HF targeting the TMAO metabolite of the intestinal flora may update the treatment concept in HF and improve its therapeutic effect.
, , Christoffer Wiingaard, Emil Loldrup Fosbøl, Andreas Birkedal Glenthøj, Nikolaj Ihlemann, Sabine Ute Alice Gill, Ulrik Christiansen, Hanne Elming, Niels Eske Bruun, et al.
Published: 5 October 2021
by BMJ
Abstract:
Objective To assess the prevalence and severity of anaemia in patients with left-sided infective endocarditis (IE) and association with mortality. Methods In the Partial Oral versus Intravenous Antibiotic Treatment of Endocarditis trial, 400 patients with IE were randomised to conventional or partial oral antibiotic treatment after stabilisation of infection, showing non-inferiority. Haemoglobin (Hgb) levels were measured at randomisation. Primary outcomes were all-cause mortality after 6 months and 3 years. Patients who underwent valve surgery were excluded due to competing reasons for anaemia. Results Out of 400 patients with IE, 248 (mean age 70.6 years (SD 11.1), 62 women (25.0%)) were medically managed; 37 (14.9%) patients had no anaemia, 139 (56.1%) had mild anaemia (Hgb <8.1 mmol/L in men and Hgb <7.5 mmol/L in women and Hgb ≥6.2 mmol/L) and 72 (29.0%) had moderate to severe anaemia (Hgb <6.2 mmol/L). Mortality rates in patients with no anaemia, mild anaemia and moderate to severe anaemia were 2.7%, 3.6% and 15.3% at 6-month follow-up and 13.5%, 20.1% and 34.7% at 3-year follow-up, respectively. Moderate to severe anaemia was associated with higher mortality after 6 months (HR 4.81, 95% CI 1.78 to 13.0, p=0.002) and after 3 years (HR 2.14, 95% CI 1.27 to 3.60, p=0.004) and remained significant after multivariable adjustment. Conclusion Moderate to severe anaemia was present in 29% of patients with medically treated IE after stabilisation of infection and was independently associated with higher mortality within the following 3 years. Further investigations are warranted to determine whether intensified treatment of anaemia in patients with IE might improve outcome.
, Ivan Javier Nuñez-Gil, Enrica Vitale, Maria C Viana-Llamas, Begoña Reche-Martinez, Rodolfo Romero-Pareja, Gisela Feltez Guzman, Inmaculada Fernandez Rozas, , Víctor Manuel Becerra-Muñoz, et al.
Published: 5 October 2021
by BMJ
Abstract:
Background Standard therapy for COVID-19 is continuously evolving. Autopsy studies showed high prevalence of platelet-fibrin-rich microthrombi in several organs. The aim of the study was therefore to evaluate the safety and efficacy of antiplatelet therapy (APT) in hospitalised patients with COVID-19 and its impact on survival. Methods 7824 consecutive patients with COVID-19 were enrolled in a multicentre international prospective registry (Health Outcome Predictive Evaluation-COVID-19 Registry). Clinical data and in-hospital complications were recorded. Data on APT, including aspirin and other antiplatelet drugs, were obtained for each patient. Results During hospitalisation, 730 (9%) patients received single APT (93%, n=680) or dual APT (7%, n=50). Patients treated with APT were older (74±12 years vs 63±17 years, p<0.01), more frequently male (68% vs 57%, p<0.01) and had higher prevalence of diabetes (39% vs 16%, p<0.01). Patients treated with APT showed no differences in terms of in-hospital mortality (18% vs 19%, p=0.64), need for invasive ventilation (8.7% vs 8.5%, p=0.88), embolic events (2.9% vs 2.5% p=0.34) and bleeding (2.1% vs 2.4%, p=0.43), but had shorter duration of mechanical ventilation (8±5 days vs 11±7 days, p=0.01); however, when comparing patients with APT versus no APT and no anticoagulation therapy, APT was associated with lower mortality rates (log-rank p<0.01, relative risk 0.79, 95% CI 0.70 to 0.94). On multivariable analysis, in-hospital APT was associated with lower mortality risk (relative risk 0.39, 95% CI 0.32 to 0.48, p<0.01). Conclusions APT during hospitalisation for COVID-19 could be associated with lower mortality risk and shorter duration of mechanical ventilation, without increased risk of bleeding. Trial registration number NCT04334291.
Jessica H Knight, Amber Leila Sarvestani, Chizitam Ibezim, Elizabeth Turk, Courtney E McCracken, Bahaaldin Alsoufi, James St Louis, James H Moller, Geetha Raghuveer, Lazaros K Kochilas
Published: 5 October 2021
by BMJ
Abstract:
Objective The ideal valve substitute for surgical intervention of congenital aortic valve disease in children remains unclear. Data on outcomes beyond 10–15 years after valve replacement are limited but important for evaluating substitute longevity. We aimed to describe up to 25-year death/cardiac transplant by type of valve substitute and assess the potential impact of treatment centre. Our hypothesis was that patients with pulmonic valve autograft would have better survival than mechanical prosthetic. Methods This is a retrospective cohort study from the Pediatric Cardiac Care Consortium, a multi-institutional US-based registry of paediatric cardiac interventions, linked with the National Death Index and United Network for Organ Sharing through 2019. Children (0–20 years old) receiving aortic valve replacement (AVR) from 1982 to 2003 were identified. Kaplan-Meier transplant-free survival was calculated, and Cox proportional hazard models estimated hazard ratios for mechanical AVR (M-AVR) versus pulmonic valve autograft. Results Among 911 children, the median age at AVR was 13.4 years (IQR=8.4–16.5) and 73% were male. There were 10 cardiac transplants and 153 deaths, 5 after transplant. The 25-year transplant-free survival post AVR was 87.1% for autograft vs 76.2% for M-AVR and 72.0% for tissue (bioprosthetic or homograft). After adjustment, M-AVR remained related to increased mortality/transplant versus autograft (HR=1.9, 95% CI=1.1 to 3.4). Surprisingly, survival for patients with M-AVR, but not autograft, was lower for those treated in centres with higher in-hospital mortality. Conclusion Pulmonic valve autograft provides the best long-term outcomes for children with aortic valve disease, but AVR results may depend on a centre’s experience or patient selection.
, Eman Alsaeed, , Suleman Aktaa, David Hogg, Matthew G D Bates, Campbel Cowan, , Chris P Gale
Published: 4 October 2021
by BMJ
Abstract:
Objective Atrial fibrillation (AF) is common and is associated with an increased risk of stroke. We aimed to systematically review and meta-analyse multivariable prediction models derived and/or validated in electronic health records (EHRs) and/or administrative claims databases for the prediction of incident AF in the community. Methods Ovid Medline and Ovid Embase were searched for records from inception to 23 March 2021. Measures of discrimination were extracted and pooled by Bayesian meta-analysis, with heterogeneity assessed through a 95% prediction interval (PI). Risk of bias was assessed using Prediction model Risk Of Bias ASsessment Tool and certainty in effect estimates by Grading of Recommendations, Assessment, Development and Evaluation. Results Eleven studies met inclusion criteria, describing nine prediction models, with four eligible for meta-analysis including 9 289 959 patients. The CHADS (Congestive heart failure, Hypertension, Age>75, Diabetes mellitus, prior Stroke or transient ischemic attack) (summary c-statistic 0.674; 95% CI 0.610 to 0.732; 95% PI 0.526–0.815), CHA2DS2-VASc (Congestive heart failure, Hypertension, Age>75 (2 points), Stroke/transient ischemic attack/thromboembolism (2 points), Vascular disease, Age 65–74, Sex category) (summary c-statistic 0.679; 95% CI 0.620 to 0.736; 95% PI 0.531–0.811) and HATCH (Hypertension, Age, stroke or Transient ischemic attack, Chronic obstructive pulmonary disease, Heart failure) (summary c-statistic 0.669; 95% CI 0.600 to 0.732; 95% PI 0.513–0.803) models resulted in a c-statistic with a statistically significant 95% PI and moderate discriminative performance. No model met eligibility for inclusion in meta-analysis if studies at high risk of bias were excluded and certainty of effect estimates was ‘low’. Models derived by machine learning demonstrated strong discriminative performance, but lacked rigorous external validation. Conclusions Models externally validated for prediction of incident AF in community-based EHR demonstrate moderate predictive ability and high risk of bias. Novel methods may provide stronger discriminative performance. Systematic review registration PROSPERO CRD42021245093.
, Nick S Nurmohamed, Jeffrey Kroon, Hein J Verberne, Evangelos Tzolos, , Aernout G Somsen, , Erik S G Stroes, Kang H Zheng, et al.
Published: 30 September 2021
by BMJ
Abstract:
Objective To assess whether patients with aortic valve stenosis (AS) with elevated lipoprotein(a) (Lp(a)) are characterised by increased valvular calcification activity compared with those with low Lp(a). Methods We performed 18F-sodium fluoride (18F-NaF) positron emission tomography/CT in patients with mild to moderate AS (peak aortic jet velocity between 2 and 4 m/s) and high versus low Lp(a) (>50 mg/dL vs <50 mg/dL, respectively). Subjects were matched according to age, gender, peak aortic jet velocity and valve morphology. We used a target to background ratio with the most diseased segment approach to compare 18F-NaF uptake. Results 52 individuals (26 matched pairs) were included in the analysis. The mean age was 66.4±5.5 years, 44 (84.6%) were men, and the mean aortic valve velocity was 2.80±0.49 m/s. The median Lp(a) was 79 (64–117) mg/dL and 7 (5–11) mg/dL in the high and low Lp(a) groups, respectively. Systolic blood pressure and low-density-lipoprotein cholesterol (corrected for Lp(a)) were significantly higher in the low Lp(a) group (141±12 mm Hg vs 128±12 mm Hg, 2.5±1.1 mmol/L vs 1.9±0.8 mmol/L). We found no difference in valvular 18F-NaF uptake between the high and low Lp(a) groups (3.02±1.26 vs 3.05±0.96, p=0.902). Linear regression analysis showed valvular calcium score to be the only significant determinant of valvular 18F-NaF uptake (β=0.63; 95% CI 0.38 to 0.88 per 1000 Agatston unit increase, p<0.001). Lp(a) was not associated with 18F-NaF uptake (β=0.17; 95% CI −0.44 to 0.88, p=0.305 for the high Lp(a) group). Conclusion Among patients with mild to moderate AS, calcification activity is predominantly determined by established calcium burden. The results do not support our hypothesis that Lp(a) is associated with valvular 18F-NaF uptake.
, Praveen Kumar Gupta, Sandeep Bansal
Published: 24 September 2021
by BMJ
Heart, Volume 107, pp 1629-1682; https://doi.org/10.1136/heartjnl-2021-319777

Ofra Barnett-Griness, Nili Stein, Antonio Kotler, Walid Saliba,
Published: 21 September 2021
by BMJ
Abstract:
Objective Clinical models such as the HAS-BLED (standing for Hypertension, Abnormal liver/renal function, Stroke history, Bleeding history or predisposition, Labile INR, Elderly, Drug/alcohol usage) were developed to predict risk of major bleeding on vitamin K antagonists/antiplatelet therapy. We aimed to develop a model that will improve the ability to predict major bleeding events in patients with non-valvular atrial fibrillation (AF) treated with new oral anticoagulants (NOACs). Methods Clalit Health Services is the largest of four integrated healthcare organisations in Israel, which insures 4.7 million patients (53% of the population). We identified in Clalit Health Services all patients with AF, new users of an NOAC (2013–2017), and followed them until first occurrence of a major bleeding event, death, switch to another oral anticoagulant, 30 days after discontinuation of NOAC or end of follow-up (31 December 2019). Importance of the candidate model variables was estimated by inclusion frequencies across forward selection algorithm applied to 50 bootstrap samples. Then, backward selection algorithm using the modified Bayesian Information Criterion for competing risks was applied to select predictors for the final model. Results 47 623 patients with AF prescribed NOAC were studied. 28 055 patients with AF, initiators of apixaban (mean age 78.7, SD 9.0), were included in the first phase and had 662 major bleeding events. Nine variables were selected for inclusion in a final points-based risk-scoring system: male sex, anaemia, thrombocytopaenia (<99×103/µL), concurrent antiplatelet therapy, hypertension, prior major bleeding, risk factors for a fall, low cholesterol level and low estimated glomerular filtration rate, with apparent area-under-curve (AUC) of 0.6546. Applicability of the model was then shown for 14 118 and 5450 patients with AF, initiators of dabigatran and rivaroxaban, where the score achieved c indices of 0.62 and 0.61, respectively. Conclusions We present a novel and simple risk score for prediction of major bleeding in patients with non-valvular AF treated with NOACs. Validation in additional cohorts is warranted.
Jose Coelho-Lima, Georgios Georgiopoulos, Javed Ahmed, Syeda E R Adil, David Gaskin, Constantinos Bakogiannis, Kateryna Sopova, Fareen Ahmed, Haaris Ahmed, Luke Spray, et al.
Published: 20 September 2021
by BMJ
Abstract:
Background and aim Although the diagnostic usefulness of high-sensitivity cardiac troponin T (hs-cTnT) is well established in ST-segment elevation myocardial infarction (STEMI), its prognostic relevance in risk stratification of patients with STEMI remains obscure. This study sought to determine the prognostic value of pre-reperfusion (admission) and post-reperfusion (12-hour) hs-cTnT in patients with STEMI treated with primary percutaneous coronary intervention (PPCI). Methods Retrospective observational longitudinal study including consecutive patients with STEMI treated with PPCI at a university hospital in the northeast of England. hs-cTnT was measured at admission to the catheterisation laboratory and 12 hours after PPCI. Clinical, procedural and laboratory data were prospectively collected during patient hospitalisation (June 2010–December 2014). Mortality data were obtained from the UK Office of National Statistics. The study endpoints were in-hospital and overall mortality. Results A total of 3113 patients were included. Median follow-up was 53 months. Admission hs-cTnT >515 ng/L (fourth quartile) was independently associated with in-hospital mortality (HR=2.53 per highest to lower quartiles; 95% CI: 1.32 to 4.85; p=0.005) after multivariable adjustment for a clinical model of mortality prediction. Likewise, admission hs-cTnT >515 ng/L independently predicted overall mortality (HR=1.27 per highest to lower quartiles; 95% CI: 1.02 to 1.59; p=0.029). Admission hs-cTnT correctly reclassified risk for in-hospital death (net reclassification index (NRI)=0.588, p<0.001) and overall mortality (NRI=0.178, p=0.001). Conversely, 12-hour hs-cTnT was not independently associated with mortality. Conclusion Admission, but not 12-hour post-reperfusion, hs-cTnT predicts mortality and improves risk stratification in the PPCI era. These results support a prognostic role for admission hs-cTnT while challenge the cost-effectiveness of routine 12-hour hs-cTnT measurements in patients with STEMI.
, Yun Soo Hong, Jong-Young Lee, Seung-Jae Lee, Yoosoo Chang, Seungho Ryu, , Juhee Cho, Eliseo Guallar, Joao A C Lima
Published: 20 September 2021
by BMJ
Heart, Volume 107, pp 1710-1716; https://doi.org/10.1136/heartjnl-2021-319346

Abstract:
Background The association of physical activity with the development and progression of coronary artery calcium (CAC) scores has not been studied. This study aimed to evaluate the prospective association between physical activity and CAC scores in apparently healthy adults. Methods Prospective cohort study of men and women free of overt cardiovascular disease who underwent comprehensive health screening examinations between 1 March 2011 and 31 December 2017. Baseline physical activity was measured using the International Physical Activity Questionnaire Short Form (IPAQ-SF) and categorised into three groups (inactive, moderately active and health-enhancing physically active (HEPA)). The primary outcome was the difference in the 5-year change in CAC scores by physical activity category at baseline. Results We analysed 25 485 participants with at least two CAC score measurements. The proportions of participants who were inactive, moderately active and HEPA were 46.8%, 38.0% and 15.2%, respectively. The estimated adjusted average baseline CAC scores (95% confidence intervals) in participants who were inactive, moderately active and HEPA were 9.45 (8.76, 10.14), 10.20 (9.40, 11.00) and 12.04 (10.81, 13.26). Compared with participants who were inactive, the estimated adjusted 5-year average increases in CAC in moderately active and HEPA participants were 3.20 (0.72, 5.69) and 8.16 (4.80, 11.53). Higher physical activity was association with faster progression of CAC scores both in participants with CAC=0 at baseline and in those with prevalent CAC. Conclusion We found a positive, graded association between physical activity and the prevalence and the progression of CAC, regardless of baseline CAC scores.
Blanca Tardajos Ayllón, Joyee Basu, , Christos P Kotanidis, Julia Ramirez, Clare Coyle
Published: 20 September 2021
by BMJ
Abstract:
Dr Blanca Tardajos Ayllón is a postdoctoral researcher at the University of Sheffield in the Department of Infection, Immunity and Cardiovascular Disease, funded by the British Heart Foundation. She obtained a BSc in Biochemistry at Universidad Autónoma de Madrid (Spain) with a year abroad at the University of York. Later, she completed an MSc in Molecular Medicine at the University of Sheffield where her work focused on the identification of mechanoreceptors that regulate endothelial apoptosis using zebrafish models. Dr Tardajos Ayllón then did her PhD in Cardiovascular Science with Professor Paul Evans. Her PhD, funded by the MRC-DiMeN Doctoral Training Partnership, focused on the role of the NF-κB transcription factor c-Rel in endothelial mechanobiology and atherosclerosis (figure 1).
, Rachael Cordina, Irina Kotchetkova, David S Celermajer
Published: 17 September 2021
by BMJ
Abstract:
Objective Patients with previously repaired aortic coarctation (CoA) are at risk of developing late surgical complications. Many patients with CoA also have a bicuspid aortic valve (BAV). We sought to determine in patients with repaired CoA whether the presence of BAV is associated with more cardiovascular reinterventions during follow-up. Methods Adults with previously repaired simple CoA were recruited from our Adult Congenital Heart Disease database (Sydney, Australia). The incidence of complications relating to the ‘CoA-site’ (descending aortic aneurysm or dissection, or recoarctation) and the ‘AV/AscAo’ (aortic valve or ascending aortic pathology) that required intervention was compared between those with BAV (‘CoA-BAV’) and without BAV (‘CoA-only’). Results Of 146 patients with repaired CoA, 101 (69%) had BAV. Age at CoA repair was similar (median 6.0 (IQR 0.5–14.0) years vs 5.0 (IQR 0.5–11.0) years, p=0.44), as was the distribution of repair types, with end-to-end repair the most common in both groups (45.9% vs 45.6%). At a median of 28 years following initial repair, a significantly higher proportion of patients with CoA-BAV required cardiovascular reintervention (45.5% vs 20.0%, p=0.003). Whereas ‘CoA-site’ complications were more common than ‘AV/AscAo’ complications in patients with CoA only (13.3% and 0%, respectively), patients with CoA-BAV had a high prevalence of both ‘CoA-site’ as well as ‘AV/AscAo’ complications (19.8% and 21.8%, respectively). Overall survival was similar (p=0.42). Conclusion In adults with repaired CoA, patients with CoA-BAV are more than twice as likely to require cardiovascular reintervention by early-to-mid-adult life compared with those with CoA alone. Despite this, no difference in survival outcomes was observed.
, Sung-Ji Park, Seung-Ah Lee, Sahmin Lee, , , Sung-Cheol Yun, Geu-Ru Hong, Jong-Min Song, , et al.
Published: 15 September 2021
by BMJ
Abstract:
Objective The decision to perform percutaneous mitral commissurotomy (PMC) on asymptomatic patients requires careful weighing of the potential benefits against the risks of PMC, and we conducted a multicentre, randomised trial to compare long-term outcomes of early PMC and conventional treatment in asymptomatic, severe mitral stenosis (MS). Methods We randomly assigned asymptomatic patients with severe MS (defined as mitral valve area between 1.0 and 1.5 cm2) to early PMC (84 patients) or to conventional treatment (83 patients). The primary endpoint was a composite of major cardiovascular events, including PMC-related complications, cardiovascular mortality, cerebral infarction and systemic thromboembolic events. The secondary endpoints were death from any cause and mitral valve (MV) replacement during follow-up. Results In the early PMC group, there were no PMC-related complications. During the median follow-up of 6.4 years, the composite primary endpoint occurred in seven patients in the early PMC group (8.3%) and in nine patients in the conventional treatment group (10.8%) (HR 0.77; 95% CI 0.29 to 2.07; p=0.61). Death from any cause occurred in four patients in the early PMC group (4.8%) and three patients in the conventional treatment group (3.6%) (HR 1.30; 95% CI 0.29 to 5.77). Ten patients (11.9%) in the early PMC group and 17 patients (20.5%) in the conventional treatment group underwent MV replacement (HR 0.59; 95% CI 0.27 to 1.29). Conclusions Compared with conventional treatment, early PMC did not significantly reduce the incidence of cardiovascular events among asymptomatic patients with severe MS during the median follow-up of 6 years. Trial registration number NCT01406353.
Ibrahim Talal Fazmin, Roy Zhang, Claire A Martin
Published: 14 September 2021
by BMJ
Heart, Volume 107, pp 1543-1602; https://doi.org/10.1136/heartjnl-2021-319721

, , Brittany Dutton, Steve E Humphries, Hasidah Abdul Hamid, Laura Condon, Stephen F Weng, Joe Kai
Published: 14 September 2021
by BMJ
Abstract:
Objective Familial hypercholesterolaemia (FH) is a common inherited disorder that remains mostly undetected in the general population. Through FH case-finding and direct access to genetic testing in primary care, this intervention study described the genetic and lipid profile of patients found at increased risk of FH and the outcomes in those with positive genetic test results. Methods In 14 Central England general practices, a novel case-finding tool (Familial Hypercholetserolaemia Case Ascertainment Tool, FAMCAT1) was applied to the electronic health records of 86 219 patients with cholesterol readings (44.5% of total practices’ population), identifying 3375 at increased risk of FH. Of these, a cohort of 336 consenting to completing Family History Questionnaire and detailed review of their clinical data, were offered FH genetic testing in primary care. Results Genetic testing was completed by 283 patients, newly identifying 16 with genetically confirmed FH and 10 with variants of unknown significance. All 26 (9%) were recommended for referral and 19 attended specialist assessment. In a further 153 (54%) patients, the test suggested polygenic hypercholesterolaemia who were managed in primary care. Total cholesterol and low-density lipoprotein-cholesterol levels were higher in those patients with FH-causing variants than those with other genetic test results (p=0.010 and p=0.002). Conclusion Electronic case-finding and genetic testing in primary care could improve identification of FH; and the better targeting of patients for specialist assessment. A significant proportion of patients identified at risk of FH are likely to have polygenic hypercholesterolaemia. There needs to be a clearer management plan for these individuals in primary care. Trial registration number NCT03934320.
Sarah Gribbin, Joanne Enticott, Allison M Hodge, Lisa Moran, Eleanor Thong, Anju Joham,
Published: 11 September 2021
by BMJ
Abstract:
Background Conflicting evidence surrounds the effect of dietary macronutrient intake (fat, carbohydrate and protein) on cardiovascular disease (CVD), particularly in women. Methods Women (aged 50–55 years) were recruited into the Australian Longitudinal Study on Women’s Health. Women were divided into quintiles according to their carbohydrate and saturated fat intake as a percentage of total energy intake (TEI). The primary endpoint was new-onset CVD (heart disease/stroke). Secondary endpoints included all-cause mortality, incident hypertension, obesity and/or diabetes mellitus. Multivariate logistic regression models assessed for associations with the primary and secondary endpoints, with adjustment for confounders. Results A total of 9899 women (mean age 52.5±1.5 years) were followed for 15 years, with 1199 incident CVD and 470 deaths. On multivariable analysis, higher carbohydrate intake was associated with lower CVD risk (ptrend<0.01), with the lowest CVD risk for quintile 3 (41.0%–44.3% energy as carbohydrate) versus quintile 1 (<37.1% energy as carbohydrate) (OR 0.56, 95% CI 0.35 to 0.91, p=0.02). There was no significant association between carbohydrate intake and mortality (ptrend=0.69) or between saturated fat intake and CVD (ptrend=0.29) or mortality (ptrend=0.25). Both increasing saturated fat and carbohydrate intake were significantly inversely associated with hypertension, diabetes mellitus and obesity (ptrend<0.01 for all). Conclusions In middle-aged Australian women, moderate carbohydrate intake (41.0%–44.3% of TEI) was associated with the lowest risk of CVD, without an effect on total mortality. Increasing saturated fat intake was not associated with CVD or mortality and instead correlated with lower rates of diabetes, hypertension and obesity.
, Ning Tan, Yong Huo, Shiqun Chen, Jin Liu, Yun-Dai Chen, Keng Wu, Guifu Wu, Kaihong Chen, Jianfeng Ye, et al.
Published: 11 September 2021
by BMJ
Abstract:
Objective To evaluate the efficacy of aggressive hydration compared with general hydration for contrast-induced acute kidney injury (CI-AKI) prevention among patients with ST-elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (pPCI). Methods The Aggressive hydraTion in patients with STEMI undergoing pPCI to prevenT Contrast-Induced Acute Kidney Injury study is an open-label, randomised controlled study at 15 teaching hospitals in China. A total of 560 adult patients were randomly assigned (1:1) to receive aggressive hydration or general hydration treatment. Aggressive hydration group received preprocedural loading dose of 125/250 mL normal saline within 30 min, followed by postprocedural hydration performed for 4 hours under left ventricular end-diastolic pressure guidance and additional hydration until 24 hours after pPCI. General hydration group received ≤500 mL 0.9% saline at 1 mL/kg/hour for 6 hours after randomisation. The primary end point is CI-AKI, defined as a >25% or 0.5 mg/dL increased in serum creatinine from baseline during the first 48–72 hours after primary angioplasty. The safety end point is acute heart failure. Results From July 2014 to May 2018, 469 patients were enrolled in the final analysis. CI-AKI occurred less frequently in aggressive hydration group than in general hydration group (21.8% vs 31.1%; risk ratio (RR) 0.70, 95% CI 0.52 to 0.96). Acute heart failure did not significantly differ between the aggressive hydration group and the general hydration group (8.1% vs 6.4%, RR 1.13, 95% CI 0.66 to 2.44). Several subgroup analysis showed the better effect of aggressive hydration in CI-AKI prevention in male, renal insufficient and non-anterior myocardial infarction participants. Conclusions Comparing with general hydration, the peri-operative aggressive hydration seems to be safe and effective in preventing CI-AKI among patients with STEMI undergoing pPCI.
, Javier Lopez, Isidre Vilacosta, Carmen Saéz, Gonzalo Cabezón, Carmen Olmos, Adrián Jerónimo, Javier B Pérez, Salvatore De Stefano, Luis Maroto, et al.
Published: 11 September 2021
by BMJ
Abstract:
Objective To evaluate the prognostic impact of urgent cardiac surgery on the prognosis of left-sided infective endocarditis (LSIE) and its relationship to the basal risk of the patient and to the surgical indication. Methods 605 patients with LSIE and formal surgical indication were consecutively recruited between 2000 and 2020 among three tertiary centres: 405 underwent surgery during the active phase of the disease and 200 did not despite having indication. The prognostic impact of urgent surgery was evaluated by multivariable analysis and propensity score analysis. We studied the benefit of surgery according to baseline mortality risk defined by the ENDOVAL score and according to surgical indication. Results Surgery is an independent predictor of survival in LSIE with surgical indication both by multivariable analysis (OR 0.260, 95% CI 0.162 to 0.416) and propensity score (mortality 40% vs 66%, p<0.001). Its greatest prognostic benefit is seen in patients at highest risk (predicted mortality 80%–100%: OR 0.08, 95% CI 0.021 to 0.299). The benefit of surgery is especially remarkable for uncontrolled infection indication (OR 0.385, 95% CI 0.194 to 0.765), even in combination with heart failure (OR 0.220, 95% CI 0.077 to 0.632). Conclusions Surgery during active LSIE seems to significantly reduce in-hospital mortality. The higher the risk, the higher the improvement in outcome.
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