Journal: Heart

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Abstract

Sacubitril/valsartan in the treatment of systemic right ventricular failure.

Zandstra TE, Nederend M, Jongbloed MRM, Kiès P, ... Schalij MJ, Egorova AD
Objective
Pharmacological options for patients with a failing systemic right ventricle (RV) in the context of transposition of the great arteries (TGA) after atrial switch or congenitally corrected TGA (ccTGA) are not well defined. This study aims to investigate the feasibility and effects of sacubitril/valsartan treatment in a single-centre cohort of patients.
Methods
Data on all consecutive adult patients (n=20, mean age 46 years, 50% women) with a failing systemic RV in a biventricular circulation treated with sacubitril/valsartan in our centre are reported. Patients with a systemic RV ejection fraction of ≤35% who were symptomatic despite treatment with β-blocker and ACE-inhibitor/angiotensin II receptor-blockers were started on sacubitril/valsartan. This cohort underwent structural follow-up including echocardiography, exercise testing, laboratory investigations and quality of life (QOL) assessment.
Results
Six-month follow-up data were available in 18 out of 20 patients, including 12 (67%) patients with TGA after atrial switch and 6 (33%) patients with ccTGA. N-terminal pro-B-type natriuretic peptide (NT-pro-BNP) decreased significantly (950-358 ng/L, p<0.001). Echocardiographic systemic RV fractional area change and global longitudinal strain showed small improvements (19%-22%, p<0.001 and -11% to -13%, p=0.014, respectively). The 6 min walking distance improved significantly from an average of 564 to 600 m (p=0.011). The QOL domains of cognitive function, sleep and vitality improved (p=0.015, p=0.007 and p=0.037, respectively).
Conclusions
We describe the first patient cohort with systemic RV failure treated with sacubitril/valsartan. Treatment appears feasible with improvements in NT-pro-BNP and echocardiographic function. Our positive results show the potential of sacubitril/valsartan for this patient population.

© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY. Published by BMJ.

Heart: 30 Oct 2021; 107:1725-1730
Zandstra TE, Nederend M, Jongbloed MRM, Kiès P, ... Schalij MJ, Egorova AD
Heart: 30 Oct 2021; 107:1725-1730 | PMID: 33452121
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Abstract

Pregnancy outcome in thoracic aortic disease data from the Registry Of Pregnancy And Cardiac disease.

Campens L, Baris L, Scott NS, Broberg CS, ... Roos-Hesselink JW, ROPAC investigators group
Background
Cardiovascular disease is the leading cause of death during pregnancy with thoracic aortic dissection being one of the main causes. Thoracic aortic disease is commonly related to hereditary disorders and congenital heart malformations such as bicuspid aortic valve (BAV). Pregnancy is considered a high risk period in women with underlying aortopathy.
Methods
The ESC EORP Registry Of Pregnancy And Cardiac disease (ROPAC) is a prospective global registry that enrolled 5739 women with pre-existing cardiac disease. With this analysis, we aim to study the maternal and fetal outcome of pregnancy in women with thoracic aortic disease.
Results
Thoracic aortic disease was reported in 189 women (3.3%). Half of them were patients with Marfan syndrome (MFS), 26% had a BAV, 8% Turner syndrome, 2% vascular Ehlers-Danlos syndrome and 11% had no underlying genetic defect or associated congenital heart defect. Aortic dilatation was reported in 58% of patients and 6% had a history of aortic dissection. Four patients, of whom three were patients with MFS, had an acute aortic dissection (three type A and one type B aortic dissection) without maternal or fetal mortality. No complications occurred in women with a history of aortic dissection. There was no significant difference in median fetal birth weight if treated with a beta-blocker or not (2960 g (2358-3390 g) vs 3270 g (2750-3570 g), p value 0.25).
Conclusion
This ancillary analysis provides the largest prospective data review on pregnancy risk for patients with thoracic aortic disease. Overall pregnancy outcomes in women with thoracic aortic disease followed according to current guidelines are good.

© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

Heart: 30 Oct 2021; 107:1704-1709
Campens L, Baris L, Scott NS, Broberg CS, ... Roos-Hesselink JW, ROPAC investigators group
Heart: 30 Oct 2021; 107:1704-1709 | PMID: 33468574
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Abstract

Antiplatelet therapy in patients with myocardial infarction without obstructive coronary artery disease.

Bossard M, Gao P, Boden W, Steg G, ... Yusuf S, Mehta SR
Objective
Approximately 10% of patients with myocardial infarction (MI) have no obstructive coronary artery disease. The prognosis and role of intensified antiplatelet therapy in those patients were evaluated.
Methods
We analysed data from the Clopidogrel and Aspirin Optimal Dose Usage to Reduce Recurrent Events-Seventh Organisation to Assess Strategies in Ischaemic Symptoms trial randomising patients with ACS referred for early intervention to receive either double-dose (600 mg, day 1; 150 mg, days 2-7; then 75 mg/day) or standard-dose (300 mg, day 1; then 75 mg/day) clopidogrel. Outcomes in patients with myocardial infarction with non-obstructive coronary arteries (MINOCA) versus those with obstructive coronary artery disease (CAD) and their relation to standard-dose versus double-dose clopidogrel were evaluated. The primary outcome was cardiovascular (CV) death, MI or stroke at 30 days.
Results
We included 23 783 patients with MI and 1599 (6.7%) with MINOCA. Patients with MINOCA were younger, presented more frequently with non-ST-segment elevation MI and had fewer comorbidities. All-cause mortality (0.6% vs 2.3%, p=0.005), CV mortality (0.6% vs 2.2%, p=0.006), repeat MI (0.5% vs 2.3%, p=0.001) and major bleeding (0.6% vs 2.4%, p<0.0001) were lower among patients with MINOCA than among those with obstructive CAD. Among patients with MINOCA, 2.1% of patients in the double-dose clopidogrel group and 0.6% in the standard-dose group experienced a primary outcome (HR 3.57, 95% CI 1.31 to 9.76), whereas in those with obstructive CAD, rates were 4.3% and 4.7%, respectively (HR 0.91, 95% CI 0.80 to 1.03; p value for interaction=0.011).
Conclusions
Patients with MINOCA are at lower risk of recurrent CV events compared with patients with MI with obstructive CAD. Compared with a standard clopidogrel-based dual antiplatelet therapy (DAPT) regimen, an intensified dosing strategy appears to offer no additional benefit with a signal of possible harm. Further randomised trials evaluating the effects of potent DAPT in patients with MINOCA are warranted.
Trial registration number
NCT00335452.

© Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.

Heart: 30 Oct 2021; 107:1739-1747
Bossard M, Gao P, Boden W, Steg G, ... Yusuf S, Mehta SR
Heart: 30 Oct 2021; 107:1739-1747 | PMID: 33504513
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Abstract

Cardiotoxicities of novel cancer immunotherapies.

Stein-Merlob AF, Rothberg MV, Ribas A, Yang EH
Immunotherapy revolutionised oncology by harnessing the native immune system to effectively treat a wide variety of malignancies even at advanced stages. Off-target immune activation leads to immune-related adverse events affecting multiple organ systems, including the cardiovascular system. In this review, we discuss the current literature describing the epidemiology, mechanisms and proposed management of cardiotoxicities related to immune checkpoint inhibitors (ICIs), chimeric antigen receptor (CAR) T-cell therapies and bispecific T-cell engagers. ICIs are monoclonal antibody antagonists that block a co-inhibitory pathway used by tumour cells to evade a T cell-mediated immune response. ICI-associated cardiotoxicities include myocarditis, pericarditis, atherosclerosis, arrhythmias and vasculitis. ICI-associated myocarditis is the most recognised and potentially fatal cardiotoxicity with mortality approaching 50%. Recently, ICI-associated dysregulation of the atherosclerotic plaque immune response with prolonged use has been linked to early progression of atherosclerosis and myocardial infarction. Treatment strategies include immunosuppression with corticosteroids and supportive care. In CAR T-cell therapy, autologous T cells are genetically engineered to express receptors targeted to cancer cells. While stimulating an effective tumour response, they also elicit a profound immune reaction called cytokine release syndrome (CRS). High-grade CRS causes significant systemic abnormalities, including cardiovascular effects such as arrhythmias, haemodynamic compromise and cardiomyopathy. Treatment with interleukin-6 inhibitors and corticosteroids is associated with improved outcomes. The evidence shows that, although uncommon, immunotherapy-related cardiovascular toxicities confer significant risk of morbidity and mortality and benefit from rapid immunosuppressive treatment. As new immunotherapies are developed and adopted, it will be imperative to closely monitor for cardiotoxicity.

© Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.

Heart: 30 Oct 2021; 107:1694-1703
Stein-Merlob AF, Rothberg MV, Ribas A, Yang EH
Heart: 30 Oct 2021; 107:1694-1703 | PMID: 33722826
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Abstract

Aspirin versus P2Y inhibitors with anticoagulation therapy for atrial fibrillation.

Fukaya H, Ako J, Yasuda S, Kaikita K, ... Matsui K, Ogawa H
Objective
Patients with coronary artery disease (CAD) and atrial fibrillation (AF) can be treated with multiple antithrombotic therapies including antiplatelet and anticoagulant therapies; however, this has the potential to increase bleeding risk. Here, we aimed to evaluate the efficacy and safety of P2Y12 inhibitors and aspirin in patients also receiving anticoagulant therapy.
Methods
We evaluated patients from the Atrial Fibrillation and Ischaemic Events with Rivaroxaban in Patients with Stable Coronary Artery Disease (AFIRE) trial who received rivaroxaban plus an antiplatelet agent; the choice of antiplatelet agent was left to the physician\'s discretion. The primary efficacy and safety end points, consistent with those of the AFIRE trial, were compared between P2Y12 inhibitors and aspirin groups. The primary efficacy end point was a composite of stroke, systemic embolism, myocardial infarction, unstable angina requiring revascularisation or death from any cause. The primary safety end point was major bleeding according to the International Society on Thrombosis and Haemostasis criteria.
Results
A total of 1075 patients were included (P2Y12 inhibitor group, n=297; aspirin group, n=778). Approximately 60% of patients were administered proton pump inhibitors (PPIs) and there was no significant difference in PPI use in the groups. There were no significant differences in the primary end points between the groups (efficacy: HR 1.31; 95% CI 0.88 to 1.94; p=0.178; safety: HR 0.79; 95% CI 0.43 to 1.47; p=0.456).
Conclusions
There were no significant differences in cardiovascular and bleeding events in patients with AF and stable CAD taking rivaroxaban with P2Y12 inhibitors or aspirin in the chronic phase.
Trial registration number
UMIN000016612; NCT02642419.

© Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.

Heart: 30 Oct 2021; 107:1731-1738
Fukaya H, Ako J, Yasuda S, Kaikita K, ... Matsui K, Ogawa H
Heart: 30 Oct 2021; 107:1731-1738 | PMID: 34261738
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Abstract

Heart failure medication dosage and survival in women and men seen at outpatient clinics.

Bots SH, Onland-Moret NC, Tulevski II, van der Harst P, ... Somsen GA, den Ruijter HM
Objective
Women with heart failure with reduced ejection fraction (HFrEF) may reach optimal treatment effect at half of the guideline-recommended medication dose. This study investigates prescription practice and its relation with survival of patients with HF in daily care.
Methods
Electronic health record data from 13 Dutch outpatient cardiology clinics were extracted for HF receiving at least one guideline-recommended HF medication. Dose changes over consecutive prescriptions were modelled using natural cubic splines. Inverse probability-weighted Cox regression was used to assess the relationship between dose (reference≥50% target dose) and all-cause mortality.
Results
The study population comprised 561 women (29% HFrEF (ejection fraction (EF)<40%), 49% heart failure with preserved ejection fraction (EF≥50%); HFpEF and 615 men (47% and 25%, respectively). During a median follow-up of 3.7 years, 252 patients died (48% women; 167 HFrEF, 84 HFpEF). Nine hundred thirty-four patients (46% women) received ACE inhibitors (ACEIs) or angiotensin receptor blockers (ARBs), 795 (48% women) beta blockers and 178 (42% women) mineralocorticoid receptor antagonists (MRAs). In both sexes, the mean target dose across prescriptions was 50% for ACEI/ARBs and beta blockers, and 100% for MRAs. ACEI/ARB dose of <50% was associated with lower mortality in women but not in men with HFrEF. This was not seen in patients with HFpEF. Beta-blocker dose was not associated with all-cause mortality.
Conclusion
Patients with HF seen in outpatient cardiology clinics receive half of the guideline-recommended medication dose. Lower ACEI/ARB dose was associated with improved survival in women with HFrEF. These results underscore the importance of (re)defining optimal medical therapy for women with HFrEF.

© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

Heart: 30 Oct 2021; 107:1748-1755
Bots SH, Onland-Moret NC, Tulevski II, van der Harst P, ... Somsen GA, den Ruijter HM
Heart: 30 Oct 2021; 107:1748-1755 | PMID: 34261736
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Abstract

Analysis of sex differences in the clinical presentation, management and prognosis of infective endocarditis in Spain.

Varela Barca L, Vidal-Bonnet L, Fariñas MC, Muñoz P, ... Lopez-Menendez J, GAMES Investigators
Introduction
Sex-dependent differences of infective endocarditis (IE) have been reported. Women suffer from IE less frequently than men and tend to present more severe manifestations. Our objective was to analyse the sex-based differences of IE in the clinical presentation, treatment, and prognosis.
Material and methods
We analysed the sex differences in the clinical presentation, modality of treatment and prognosis of IE in a national-level multicentric cohort between 2008 and 2018. All data were prospectively recorded by the GAMES cohort (Spanish Collaboration on Endocarditis).
Results
A total of 3451 patients were included, of whom 1105 were women (32.0%). Women were older than men (mean age, 68.4 vs 64.5). The most frequently affected valves were the aortic valve in men (50.6%) and mitral valve in women (48.7%). Staphylococcus aureus aetiology was more frequent in women (30.1% vs 23.1%; p<0.001).Surgery was performed in 38.3% of women and 50% of men. After propensity score (PS) matching for age and estimated surgical risk (European System for Cardiac Operative Risk Evaluation II (EuroSCORE II)), the analysis of the matched cohorts revealed that women were less likely to undergo surgery (OR 0.74; 95% CI 0.59 to 0.91; p=0.05).The observed overall in-hospital mortality was 32.8% in women and 25.7% in men (OR for the mortality of female sex 1.41; 95% CI 1.21 to 1.65; p<0.001). This statistical difference was not modified after adjusting for all possible confounders.
Conclusions
Female sex was an independent factor related to mortality after adjusting for confounders. In addition, women were less frequently referred for surgical treatment.

© Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.

Heart: 30 Oct 2021; 107:1717-1724
Varela Barca L, Vidal-Bonnet L, Fariñas MC, Muñoz P, ... Lopez-Menendez J, GAMES Investigators
Heart: 30 Oct 2021; 107:1717-1724 | PMID: 34290038
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Abstract

Physical activity and the progression of coronary artery calcification.

Sung KC, Hong YS, Lee JY, Lee SJ, ... Guallar E, Lima JAC
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.

© Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.

Heart: 30 Oct 2021; 107:1710-1716
Sung KC, Hong YS, Lee JY, Lee SJ, ... Guallar E, Lima JAC
Heart: 30 Oct 2021; 107:1710-1716 | PMID: 34544807
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Abstract

Percutaneous management of paravalvular leaks.

Giblett JP, Williams LK, Moorjani N, Calvert PA
Paravalvular leak (PVL) is a challenging complication of valve replacement surgery that can cause heart failure and haemolysis. Surgical repair is the traditional treatment for severe, symptomatic PVL, but many patients with PVL fall into high-risk categories for redo surgery. Percutaneous techniques for closure of PVL have been increasingly refined over the last decade with availability of approved purpose-specific devices for closure. Percutaneous closure requires a heart team approach, with attention paid to appropriate preprocedural and periprocedural imaging to ensure a successful closure with minimal residual leak or complication. There are limited studies addressing the selection of a percutaneous approach to PVL. No randomised trials comparing surgical and percutaneous repair have been conducted. Large national registries from the UK and Ireland and from Spain have demonstrated that high rates of technical success can be achieved, with mortality comparable with surgical repair. Six retrospective studies comparing surgical and percutaneous approaches have been published. These broadly show comparable technical success between the interventions, with reduced short-term mortality among patients treated percutaneously. Long-term outcomes were similar between both treatment options. Percutaneous repair is an attractive treatment option in many patients due to its reduced invasiveness and quicker recovery period. However, more prospective studies are needed to validate its place in the armamentarium of the heart team.

© Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.

Heart: 21 Oct 2021; epub ahead of print
Giblett JP, Williams LK, Moorjani N, Calvert PA
Heart: 21 Oct 2021; epub ahead of print | PMID: 34686568
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Abstract

Prognostic value of coronary computed tomography angiographic derived fractional flow reserve: a systematic review and meta-analysis.

Nørgaard BL, Gaur S, Fairbairn TA, Douglas PS, ... Leipsic J, Abdulla J
Objectives
To obtain more powerful assessment of the prognostic value of fractional flow reserveCT testing we performed a systematic literature review and collaborative meta-analysis of studies that assessed clinical outcomes of CT-derived calculation of FFR (FFRCT) (HeartFlow) analysis in patients with stable coronary artery disease (CAD).
Methods
We searched PubMed and Web of Science electronic databases for published studies that evaluated clinical outcomes following fractional flow reserveCT testing between 1 January 2010 and 31 December 2020. The primary endpoint was defined as \'all-cause mortality (ACM) or myocardial infarction (MI)\' at 12-month follow-up. Exploratory analyses were performed using major adverse cardiovascular events (MACEs, ACM+MI+unplanned revascularisation), ACM, MI, spontaneous MI or unplanned (>3 months) revascularisation as the endpoint.
Results
Five studies were identified including a total of 5460 patients eligible for meta-analyses. The primary endpoint occurred in 60 (1.1%) patients, 0.6% (13/2126) with FFRCT>0.80% and 1.4% (47/3334) with FFRCT ≤0.80 (relative risk (RR) 2.31 (95% CI 1.29 to 4.13), p=0.005). Likewise, MACE, MI, spontaneous MI or unplanned revascularisation occurred more frequently in patients with FFRCT ≤0.80 versus patients with FFRCT >0.80. Each 0.10-unit FFRCT reduction was associated with a greater risk of the primary endpoint (RR 1.67 (95% CI 1.47 to 1.87), p<0.001).
Conclusions
The 12-month outcomes in patients with stable CAD show low rates of events in those with a negative FFRCT result, and lower risk of an unfavourable outcome in patients with a negative test result compared with patients with a positive test result. Moreover, the FFRCT numerical value was inversely associated with outcomes.

© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

Heart: 21 Oct 2021; epub ahead of print
Nørgaard BL, Gaur S, Fairbairn TA, Douglas PS, ... Leipsic J, Abdulla J
Heart: 21 Oct 2021; epub ahead of print | PMID: 34686567
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Abstract

Contrasting trends in heart failure incidence in younger and older New Zealanders, 2006-2018.

Chan DZL, Kerr A, Grey C, Selak V, ... Poppe K, Doughty RN
Objective
Studies indicate that age-standardised heart failure (HF) incidence has been decreasing internationally; however, contrasting trends in different age groups have been reported, with rates increasing in younger people and decreasing in the elderly. We aimed to describe age-specific trends in HF incidence in New Zealand (NZ).
Methods
In this nationwide data linkage study, we used routinely collected hospitalisation data to identify incident HF hospitalisations in NZ residents aged ≥20 years between 2006 and 2018. Age-specific and age-standardised incidence rates were calculated for each calendar year. Joinpoint regression was used to compare incidence trends.
Results
116 113 incident HF hospitalisations were identified over the 13-year study period. Between 2006 and 2013, age-standardised incidence decreased from 403 to 323 per 100 000 (annual percentage change (APC) -2.6%, 95% CI -3.6 to -1.6%). This reduction then plateaued between 2013 and 2018 (APC 0.8%, 95% CI -0.8 to 2.5%). Between 2006 and 2018, rates in individuals aged 20-49 years old increased by 1.5% per year (95% CI 0.3 to 2.7%) and decreased in those aged ≥80 years old by 1.2% per year (95% CI -1.7 to -0.7%). Rates in individuals aged 50-79 years old initially declined from 2006 to 2013, and then remained stable or increased from 2013 to 2018. The proportion of HF hospitalisations associated with ischaemic heart disease decreased from 35.1% in 2006 to 28.0% in 2018.
Conclusion
HF remains an important problem in NZ. The decline in overall incidence has plateaued since 2013 due to increasing rates of HF in younger age groups despite an ongoing decline in the elderly.

© Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.

Heart: 21 Oct 2021; epub ahead of print
Chan DZL, Kerr A, Grey C, Selak V, ... Poppe K, Doughty RN
Heart: 21 Oct 2021; epub ahead of print | PMID: 34686566
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Abstract

Management and outcomes of patients with left atrial appendage thrombus prior to percutaneous closure.

Marroquin L, Tirado-Conte G, Pracoń R, Streb W, ... Rodés-Cabau J, Nombela Franco L
Objective
Left atrial appendage (LAA) thrombus has heretofore been considered a contraindication to percutaneous LAA closure (LAAC). Data regarding its management are very limited. The aim of this study was to analyse the medical and invasive treatment of patients referred for LAAC in the presence of LAA thrombus.
Methods
This multicentre observational registry included 126 consecutive patients referred for LAAC with LAA thrombus on preprocedural imaging. Treatment strategies included intensification of antithrombotic therapy (IAT) or direct LAAC. The primary and secondary endpoints were a composite of bleeding, stroke and death at 18 months, and procedural success, respectively.
Results
IAT was the preferred strategy in 57.9% of patients, with total thrombus resolution observed in 60.3% and 75.3% after initial and subsequent IAT, respectively. Bleeding complications and stroke during IAT occurred in 9.6% and 2.9%, respectively, compared with 3.8% bleeding and no embolic events in the direct LAAC group before the procedure. Procedural success was 90.5% (96.2% vs 86.3% in direct LAAC and IAT group, respectively, p=0.072), without cases of in-hospital thromboembolic complications. The primary endpoint occurred in 29.3% and device-related thrombosis was found in 12.8%, without significant difference according to treatment strategy. Bleeding complications at 18 months occurred in 22.5% vs 10.5% in the IAT and direct LAAC group, respectively (p=0.102).
Conclusion
In the presence of LAA thrombus, IAT was the initial management strategy in half of our cohort, with initial thrombus resolution in 60% of these, but with a relatively high bleeding rate (~10%). Direct LAAC was feasible, with high procedural success and absence of periprocedural embolic complications. However, a high rate of device-related thrombosis was detected during follow-up.

© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

Heart: 21 Oct 2021; epub ahead of print
Marroquin L, Tirado-Conte G, Pracoń R, Streb W, ... Rodés-Cabau J, Nombela Franco L
Heart: 21 Oct 2021; epub ahead of print | PMID: 34686564
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Abstract

Atrial fibrillation following transcatheter atrial septal defect closure: a systematic review and meta-analysis.

Himelfarb JD, Shulman H, Olesovsky CJ, Rumman RK, ... Horlick E, Abrahamyan L
Objective
The ostium secundum atrial septal defect (ASD) is among the most common congenital cardiac anomalies diagnosed in adulthood. A known complication of transcatheter ASD closure is the development of new-onset atrial fibrillation and flutter (AFi/AFl). These arrhythmias confer an increased risk of postoperative stroke, thrombus formation and systemic emboli. This systematic review examines the burden of de novo AFi/AFl in adults following transcatheter closure and seeks to identify risk factors for AFi/AFl development.
Methods
Studies were identified by a search of MEDLINE, EMBASE and Cochrane databases from inception until 29 April 2020. A meta-analysis of AFi/AFl incidence was performed using a random-effects model.
Results
A total of 31 studies met inclusion criteria, comprising 4788 adult patients without a history of AFi/AFl. Twenty-three studies were included in quantitative synthesis and demonstrated an overall incidence rate of 1.82 patients per 100 person-years of follow-up (I2=83%). In studies that enrolled only patients ≥60 years old, the incidence was 5.21 patients per 100 person-years (I2=0%). Studies with follow-up duration ≤2 years reported an incidence of 4.05 per 100 person-years (I2=55%) compared with a rate of 1.19 per 100 person-years (I2=85%) for studies with follow-up duration >2 years.
Conclusions
The incidence of new-onset AFi/AFl is relatively low following transcatheter closure of secundum ASDs. The rate of de novo AFi/AFl, however, was significantly higher in elderly patients. Shorter follow-up time was associated with a higher reported incidence of AFi/AFl.

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Heart: 20 Oct 2021; epub ahead of print
Himelfarb JD, Shulman H, Olesovsky CJ, Rumman RK, ... Horlick E, Abrahamyan L
Heart: 20 Oct 2021; epub ahead of print | PMID: 34675040
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Abstract

Cardiovascular considerations for scuba divers.

Tso JV, Powers JM, Kim JH
As the popularity of scuba diving increases internationally, physicians interacting with divers in the clinical setting must be familiar with the cardiovascular stresses and risks inherent to this activity. Scuba presents a formidable cardiovascular challenge by combining unique environmental conditions with the physiologic demands of underwater exercise. Haemodynamic stresses encountered at depth include increased hydrostatic pressure leading to central shifts in plasma volume coupled with cold water stimuli leading to simultaneous parasympathetic and sympathetic autonomic responses. Among older divers and those with underlying cardiovascular risk factors, these physiologic changes increase acute cardiac risks while diving. Additional scuba risks, as a consequence of physical gas laws, include arterial gas emboli and decompression sickness. These pathologies are particularly dangerous with altered sensorium in hostile dive conditions. When present, the appropriate management of patent foramen ovale (PFO) is uncertain, but closure of PFO may reduce the risk of paradoxical gas embolism in divers with a prior history of decompression sickness. Finally, similar to other Masters-level athletes, divers with underlying traditional cardiovascular risk should undergo complete cardiac risk stratification to determine \'fitness-to-dive\'. The presence of undertreated coronary artery disease, occult cardiomyopathy, channelopathy and arrhythmias must all be investigated and appropriately treated in order to ensure diver safety. A patient-centred approach facilitating shared decision-making between divers and experienced practitioners should be utilised in the management of prospective scuba divers.

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Heart: 19 Oct 2021; epub ahead of print
Tso JV, Powers JM, Kim JH
Heart: 19 Oct 2021; epub ahead of print | PMID: 34670825
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Abstract

Non-invasive markers for sudden cardiac death risk stratification in dilated cardiomyopathy.

Pooranachandran V, Nicolson W, Vali Z, Li X, Ng GA
Dilated cardiomyopathy (DCM) is a common yet challenging cardiac disease. Great strides have been made in improving DCM prognosis due to heart failure but sudden cardiac death (SCD) due to ventricular arrhythmias remains significant and challenging to predict. High-risk patients can be effectively managed with implantable cardioverter defibrillators (ICDs) but because identification of what is high risk is very limited, many patients unnecessarily experience the morbidity associated with an ICD implant and many others are not identified and have preventable mortality. Current guidelines recommend use of left ventricular ejection fraction and New York Heart Association class as the main markers of risk stratification to identify patients who would be at higher risk of SCD. However, when analysing the data from the trials that these recommendations are based on, the number of patients in whom an ICD delivers appropriate therapy is modest. In order to improve the effectiveness of therapy with an ICD, the patients who are most likely to benefit need to be identified. This review article presents the evidence behind current guideline-directed SCD risk markers and then explores new potential imaging, electrophysiological and genetic risk markers for SCD in DCM.

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Heart: 19 Oct 2021; epub ahead of print
Pooranachandran V, Nicolson W, Vali Z, Li X, Ng GA
Heart: 19 Oct 2021; epub ahead of print | PMID: 34670824
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Abstract

Brugada syndrome: update and future perspectives.

Marsman EMJ, Postema PG, Remme CA
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.

© Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.

Heart: 13 Oct 2021; epub ahead of print
Marsman EMJ, Postema PG, Remme CA
Heart: 13 Oct 2021; epub ahead of print | PMID: 34649929
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Abstract

Influenza vaccine and risk of acute myocardial infarction in a population-based case-control study.

de Abajo FJ, Rodríguez-Martín S, Barreira D, Rodríguez-Miguel A, ... Gil M, García-Lledó A
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.

© Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.

Heart: 12 Oct 2021; epub ahead of print
de Abajo FJ, Rodríguez-Martín S, Barreira D, Rodríguez-Miguel A, ... Gil M, García-Lledó A
Heart: 12 Oct 2021; epub ahead of print | PMID: 34645644
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Abstract

Anticoagulant prescribing for atrial fibrillation and risk of incident dementia.

Cadogan SL, Powell E, Wing K, Wong AY, Smeeth L, Warren-Gash C
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.

© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY. Published by BMJ.

Heart: 12 Oct 2021; epub ahead of print
Cadogan SL, Powell E, Wing K, Wong AY, Smeeth L, Warren-Gash C
Heart: 12 Oct 2021; epub ahead of print | PMID: 34645643
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Abstract

Association of age with clinical features and ablation outcomes of paroxysmal supraventricular tachycardias.

Ávila P, Calvo D, Tamargo M, Uribarri A, ... Fernández-Avilés F, González-Torrecilla E
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 (p<0.001 for both). Age was not associated with catheter ablation acute success, periprocedural complications or 1-year recurrence rates (p>0.05 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.

© Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.

Heart: 10 Oct 2021; epub ahead of print
Ávila P, Calvo D, Tamargo M, Uribarri A, ... Fernández-Avilés F, González-Torrecilla E
Heart: 10 Oct 2021; epub ahead of print | PMID: 34635482
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Abstract

MRI and CT coronary angiography in survivors of COVID-19.

Singh T, Kite TA, Joshi SS, Spath NB, ... Dweck M, McCann GP
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.

© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

Heart: 05 Oct 2021; epub ahead of print
Singh T, Kite TA, Joshi SS, Spath NB, ... Dweck M, McCann GP
Heart: 05 Oct 2021; epub ahead of print | PMID: 34615668
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Abstract

Race, sex and age disparities in echocardiography among Medicare beneficiaries in an integrated healthcare system.

Hyland PM, Xu J, Shen C, Markson LJ, Manning WJ, Strom JB
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.

© Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.

Heart: 05 Oct 2021; epub ahead of print
Hyland PM, Xu J, Shen C, Markson LJ, Manning WJ, Strom JB
Heart: 05 Oct 2021; epub ahead of print | PMID: 34615667
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Abstract

Trimethylamine oxide: a potential target for heart failure therapy.

Lv S, Wang Y, Zhang W, Shang H
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.

© Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.

Heart: 04 Oct 2021; epub ahead of print
Lv S, Wang Y, Zhang W, Shang H
Heart: 04 Oct 2021; epub ahead of print | PMID: 34611047
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Abstract

Antiplatelet therapy and outcome in COVID-19: the Health Outcome Predictive Evaluation Registry.

Santoro F, Nuñez-Gil IJ, Vitale E, Viana-Llamas MC, ... Fernandez-Ortiz A, Brunetti ND
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.

© Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.

Heart: 04 Oct 2021; epub ahead of print
Santoro F, Nuñez-Gil IJ, Vitale E, Viana-Llamas MC, ... Fernandez-Ortiz A, Brunetti ND
Heart: 04 Oct 2021; epub ahead of print | PMID: 34611045
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Abstract

Multicentre comparative analysis of long-term outcomes after aortic valve replacement in children.

Knight JH, Sarvestani AL, Ibezim C, Turk E, ... Raghuveer G, Kochilas LK
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.

© Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.

Heart: 04 Oct 2021; epub ahead of print
Knight JH, Sarvestani AL, Ibezim C, Turk E, ... Raghuveer G, Kochilas LK
Heart: 04 Oct 2021; epub ahead of print | PMID: 34611043
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Abstract

Severity of anaemia and association with all-cause mortality in patients with medically managed left-sided endocarditis.

Pries-Heje MM, Hasselbalch RB, Wiingaard C, Fosbøl EL, ... Iversen K, Bundgaard H
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.

© Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.

Heart: 04 Oct 2021; epub ahead of print
Pries-Heje MM, Hasselbalch RB, Wiingaard C, Fosbøl EL, ... Iversen K, Bundgaard H
Heart: 04 Oct 2021; epub ahead of print | PMID: 34611042
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Abstract

Prediction of incident atrial fibrillation in community-based electronic health records: a systematic review with meta-analysis.

Nadarajah R, Alsaeed E, Hurdus B, Aktaa S, ... Wu J, Gale CP
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.

© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY. Published by BMJ.

Heart: 03 Oct 2021; epub ahead of print
Nadarajah R, Alsaeed E, Hurdus B, Aktaa S, ... Wu J, Gale CP
Heart: 03 Oct 2021; epub ahead of print | PMID: 34607811
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Abstract

What is the normal composition of pericardial fluid?

Buoro S, Tombetti E, Ceriotti F, Simon C, ... Imazio M, Brucato A
Objective
Biochemical and cytological pericardial fluid (PF) analysis is essentially based on the knowledge of pleural fluid composition. The aim of the present study is to identify reference intervals (RIs) for PF according to state-of-art methodological standards.
Methods
We prospectively collected and analysed the PF and venous blood of consecutive subjects undergoing elective open-heart surgery from July 2017 to October 2018. Exclusion criteria for study enrolment were evidence of pericardial diseases at preoperatory workup or at intraoperatory assessment, or any other condition that could affect PF analysis.
Results
The final study sample included 120 patients (median age 69 years, 83 men, 69.1%). The main findings were (1) High levels of proteins, albumin and lactate dehydrogenase (LDH), but not of glucose and cholesterol (2) High cellularity, mainly represented by mesothelial cells. RIs for pericardial biochemistry were: protein content 1.7-4.6 g/dL PF/serum protein ratio 0.29-0.83, albumin 1.19-3.06 g/dL, pericardium-to-serum albumin gradient 0.18-2.37 g/dL, LDH 141-2613 U/L, PF/serum LDH ratio 0.40-2.99, glucose 80-134 mg/dL, total cholesterol 12-69 mg/dL, PF/serum cholesterol ratio 0.07-0.51. RIs for pericardial cells by optic microscopy were: 278-5608 × 106 nucleated cells/L, 40-3790 × 106 mesothelial cells/L, 35-2210 × 106 leucocytes/L, 19-1634 × 106 lymphocytes/L.
Conclusions
PF is rich in nucleated cells, protein, albumin, LDH, at levels consistent with inflammatory exudates in other biological fluids. Physicians should stop to interpret PF as exudate or transudate according to tools not validated for this setting.

© Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.

Heart: 29 Sep 2021; 107:1584-1590
Buoro S, Tombetti E, Ceriotti F, Simon C, ... Imazio M, Brucato A
Heart: 29 Sep 2021; 107:1584-1590 | PMID: 33177118
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Impact:
Abstract

Effect of blood pressure lowering drugs and antibiotics on abdominal aortic aneurysm growth: a systematic review and meta-analysis.

Golledge J, Singh TP
Objective
There is currently no medical treatment proven to limit abdominal aortic aneurysm (AAA) progression. The aim of this systematic review and meta-analysis was to pool data from previous randomised controlled trials assessing the efficacy of blood pressure-lowering and antibiotic medications in limiting AAA growth and AAA-related events, that is, rupture or repair.
Methods
A systematic literature search was performed to identify randomised controlled trials that examined the efficacy of blood pressure-lowering medications or antibiotics in reducing AAA growth and AAA-related events. AAA growth (mm/year) was measured by ultrasound or computed tomography imaging. Meta-analyses were performed using random effects models. A subanalysis was conducted including trials that investigated tetracycline or macrolide antibiotics.
Results
Ten randomised controlled trials including 2045 participants with an asymptomatic AAA were included. Follow-up was between 18 and 63 months. Neither blood pressure-lowering medications (mean growth±SD 2.0±2.4 vs 2.3±2.7 mm/year; standardised mean difference (SMD) -0.07, 95% CI -0.19 to 0.06; p=0.288) or antibiotics (mean growth±SD 2.6±2.1 vs 2.6±2.5 mm/year; SMD -0.11, 95% CI -0.38 to 0.16; p=0.418) reduced AAA growth or AAA-related events (blood pressure-lowering medications: 92 vs 95 events; risk ratio (RR) 0.86, 95% CI 0.66 to 1.11; p=0.244; and antibiotics: 69 vs 73 events; RR 0.93, 95% CI 0.69 to 1.25; p=0.614). The subanalysis of antibiotics showed similar results.
Conclusions
This meta-analysis suggests that neither blood pressure-lowering medications or antibiotics limit growth or clinically relevant events in people with AAAs.

© Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.

Heart: 29 Sep 2021; 107:1465-1471
Golledge J, Singh TP
Heart: 29 Sep 2021; 107:1465-1471 | PMID: 33199361
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Abstract

Bleeding and thrombotic risk in pregnant women with Fontan physiology.

Girnius A, Zentner D, Valente AM, Pieper PG, ... Mulder BJM, Veldtman GR
Background/objectives
Pregnancy may potentiate the inherent hypercoagulability of the Fontan circulation, thereby amplifying adverse events. This study sought to evaluate thrombosis and bleeding risk in pregnant women with a Fontan.
Methods
We performed a retrospective observational cohort study across 13 international centres and recorded data on thrombotic and bleeding events, antithrombotic therapies and pre-pregnancy thrombotic risk factors.
Results
We analysed 84 women with Fontan physiology undergoing 108 pregnancies, average gestation 33±5 weeks. The most common antithrombotic therapy in pregnancy was aspirin (ASA, 47 pregnancies (43.5%)). Heparin (unfractionated (UFH) or low molecular weight (LMWH)) was prescribed in 32 pregnancies (30%) and vitamin K antagonist (VKA) in 10 pregnancies (9%). Three pregnancies were complicated by thrombotic events (2.8%). Thirty-eight pregnancies (35%) were complicated by bleeding, of which 5 (13%) were severe. Most bleeds were obstetric, occurring antepartum (45%) and postpartum (42%). The use of therapeutic heparin (OR 15.6, 95% CI 1.88 to 129, p=0.006), VKA (OR 11.7, 95% CI 1.06 to 130, p=0.032) or any combination of anticoagulation medication (OR 13.0, 95% CI 1.13 to 150, p=0.032) were significantly associated with bleeding events, while ASA (OR 5.41, 95% CI 0.73 to 40.4, p=0.067) and prophylactic heparin were not (OR 4.68, 95% CI 0.488 to 44.9, p=0.096).
Conclusions
Current antithrombotic strategies appear effective at attenuating thrombotic risk in pregnant women with a Fontan. However, this comes with high (>30%) bleeding risk, of which 13% are life threatening. Achieving haemostatic balance is challenging in pregnant women with a Fontan, necessitating individualised risk-adjusted counselling and therapeutic approaches that are monitored during the course of pregnancy.

© Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.

Heart: 29 Sep 2021; 107:1390-1397
Girnius A, Zentner D, Valente AM, Pieper PG, ... Mulder BJM, Veldtman GR
Heart: 29 Sep 2021; 107:1390-1397 | PMID: 33234672
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Impact:
Abstract

Bleeding risk with rivaroxaban compared with vitamin K antagonists in patients aged 80 years or older with atrial fibrillation.

Hanon O, Vidal JS, Pisica-Donose G, Orvoën G, ... Boureau AS, SAFIR study group
Objective
Direct oral anticoagulants have been evaluated in the general population, but proper evidence for their safe use in the geriatric population is still missing. We compared the bleeding risk of a direct oral anticoagulant (rivaroxaban) and vitamin K antagonists (VKAs) among French geriatric patients with non-valvular atrial fibrillation (AF) aged ≥80 years.
Methods
We performed a sequential observational prospective cohort study, using data from 33 geriatric centres. The sample comprised 908 patients newly initiated on VKAs between September 2011 and September 2014 and 995 patients newly initiated on rivaroxaban between September 2014 and September 2017. Patients were followed up for up to 12 months. One-year risks of major, intracerebral, gastrointestinal bleedings, ischaemic stroke and all-cause mortality were compared between rivaroxaban-treated and VKA-treated patients with propensity score matching and Cox models.
Results
Major bleeding risk was significantly lower in rivaroxaban-treated patients (7.4/100 patient-years) compared with VKA-treated patients (14.6/100 patient-years) after multivariate adjustment (HR 0.66; 95% CI 0.43 to 0.99) and in the propensity score-matched sample (HR 0.53; 95% CI 0.33 to 0.85). Intracerebral bleeding occurred less frequently in rivaroxaban-treated patients (1.3/100 patient-years) than in VKA-treated patients (4.0/100 patient-years), adjusted HR 0.59 (95% CI 0.24 to 1.44) and in the propensity score-matched sample HR 0.26 (95% CI 0.09 to 0.80). Major lower bleeding risk was largely driven by lower risk of intracerebral bleeding.
Conclusions
Our study findings indicate that bleeding risk, largely driven by lower risk of intracerebral bleeding, is lower with rivaroxaban than with VKA in stroke prevention in patients ≥80 years old with non-valvular AF.

© Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.

Heart: 29 Sep 2021; 107:1376-1382
Hanon O, Vidal JS, Pisica-Donose G, Orvoën G, ... Boureau AS, SAFIR study group
Heart: 29 Sep 2021; 107:1376-1382 | PMID: 33262185
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Impact:
Abstract

N-terminal pro-brain natriuretic peptide and sudden cardiac death in hypertrophic cardiomyopathy.

Wu G, Liu J, Wang S, Yu S, ... Wang J, Song L
Objective
Elevated levels of N-terminal pro-brain natriuretic peptide (NT-proBNP) are associated with heart failure-related death in hypertrophic cardiomyopathy (HCM), but the relationship between NT-proBNP level and sudden cardiac death (SCD) in HCM remains undefined.
Methods
The study prospectively enrolled 977 unrelated patients with HCM with available NT-proBNP results who were prospectively enrolled and followed for 3.0±2.1 years. The Harrell\'s C-statistic under the receiver operating characteristic curve was calculated to evaluate discrimination performance. A combination model was constructed by adding NT-proBNP tertiles to the HCM Risk-SCD model. The correlation between log NT-proBNP level and cardiac fibrosis as measured by late gadolinium enhancement (LGE) or Masson\'s staining was analysed.
Results
During follow-up, 29 patients had SCD. Increased log NT-proBNP levels were associated with an increased risk of SCD events (adjusted HR 22.27, 95% CI 10.93 to 65.63, p<0.001). The C-statistic of NT-proBNP in predicting SCD events was 0.80 (p<0.001). The combined model significantly improved the predictive efficiency of the HCM Risk-SCD model from 0.72 to 0.81 (p<0.05), with a relative integrated discrimination improvement of 0.002 (p<0.001) and net reclassification improvement of 0.67 (p<0.001). Furthermore, log NT-proBNP levels were significantly correlated with cardiac fibrosis as detected either by LGE (r=0.257, p<0.001) or by Masson\'s trichrome staining in the myocardium (r=0.198, p<0.05).
Conclusion
NT-proBNP is an independent predictor of SCD in patients with HCM and may help with risk stratification of this disease.

© Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.

Heart: 29 Sep 2021; 107:1576-1583
Wu G, Liu J, Wang S, Yu S, ... Wang J, Song L
Heart: 29 Sep 2021; 107:1576-1583 | PMID: 33361398
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Impact:
Abstract

Prognostic value of electrocardiographic abnormalities in adults from the Brazilian longitudinal study of adults\' health.

Pinto-Filho MM, Brant LC, Dos Reis RP, Giatti L, ... Barreto SM, Ribeiro ALP
Objective
Cardiovascular diseases (CVDs) are highly preventable non-communicable diseases. ECG is a potential tool for risk stratification with respect to CVD. Our aim was to evaluate ECG\'s role in all-cause and cardiovascular mortality prediction.
Methods
Participants from the Brazilian Longitudinal Study of Adult Health, free of known CVD at baseline were included. A 12-lead ECG was obtained at baseline (2008-2010). Participants were followed up to 2018 by annual interviews. Deaths were independently reviewed. Cox as well as Fine and Grey multivariable regression models were applied to evaluate if the presence of any major electrocardiographic abnormality (MEA), defined according to the Minnesota Code system, would predict total and cardiovascular deaths. We also evaluated the Net Reclassification Index of adding MEA to the Systematic Coronary Risk Evaluation (SCORE).
Results
The 13 428 participants (median age 51 years, 45% men) were followed up for 8±1 years. All-cause and cardiovascular mortality occurred in 2.8% and 1.2% of the population, respectively. Prevalent MEA was an independent predictor of overall (HR=2.3, 95% CI 1.7 to 2.9) and cardiovascular mortality (HR=4.6, 95% CI 3.0 to 7.0) after adjustments for age, race, education and traditional cardiovascular risk factors. Adding MEA to the SCORE resulted in 9% mis-reclassification in the non-event subgroup and 33% correct reclassification in those with a fatal cardiovascular event.
Conclusion
Presence of MEA was an independent predictor of overall and cardiovascular mortality. ECG may have a role in risk prediction of cardiovascular mortality in primary care.

© Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.

Heart: 29 Sep 2021; 107:1560-1566
Pinto-Filho MM, Brant LC, Dos Reis RP, Giatti L, ... Barreto SM, Ribeiro ALP
Heart: 29 Sep 2021; 107:1560-1566 | PMID: 33361354
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Impact:
Abstract

Transcatheter tricuspid valve replacement in patients with severe tricuspid regurgitation.

Lu FL, An Z, Ma Y, Song ZG, ... Qiao F, Xu ZY
Objective
Tricuspid regurgitation (TR) is a common valvular heart disease with unsatisfactory medical therapeutics and high surgical mortality. The present study aims to evaluate the safety and effectiveness of transcatheter tricuspid valve replacement (TTVR) in high-risk patients with severe TR.
Methods
This was a compassionate multicentre study. Between September 2018 and November 2019, 46 patients with TR who were not suitable for surgery received compassionate TTVR under general anaesthesia and the guidance of trans-oesophageal echocardiography and fluoroscopy in four institutions. Access to the tricuspid valve was obtained via a minimally invasive thoracotomy and transatrial approach. Patients\' data at baseline, before discharge, 30 days and 6 months after the procedure were collected.
Results
All patients had severe TR with vena contracta width of 12.6 (11.0, 14.5) mm. Procedural success (97.8%) was achieved in all but one case with right ventricle perforation. The procedural time was 150.0 (118.8, 180.0) min. Intensive care unit time was 2.0 (1.0, 4.0) days. 6-month mortality was 17.4%. Device migration occurred in one patient (2.4%) during follow-up. Transthoracic echocardiography at 6 months after operation showed TR was significantly reduced (none/trivial in 33, mild in 4 and moderate in 1) and the primary safety end point was achieved in 38 cases (82.6%). Patients suffered from peripheral oedema and ascites decreased from 100.0% and 47.8% at baseline to 2.6% and 0.0% at 6 months.
Conclusions
The present study showed TTVR was feasible, safe and with low complication rates in patients with severe TR.

© Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.

Heart: 29 Sep 2021; 107:1664-1670
Lu FL, An Z, Ma Y, Song ZG, ... Qiao F, Xu ZY
Heart: 29 Sep 2021; 107:1664-1670 | PMID: 33419880
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Impact:
Abstract

Sex differences in heart failure hospitalisation risk following acute myocardial infarction.

Yandrapalli S, Malik A, Pemmasani G, Aronow W, ... Frishman W, Panza J
Objective
We evaluated the sex differences in 6-month heart failure (HF) hospitalisation risk in acute myocardial infarction (AMI) survivors.
Methods
For this retrospective cohort analysis, adult survivors of an AMI between January and June 2014 were identified from the US Nationwide Readmissions Database. The primary outcome was a HF hospitalisation within 6 months. Secondary outcomes were fatal HF hospitalisation and the composite of index in-hospital HF or 6-month HF hospitalisation.
Results
Of 237 549 AMI survivors, females (37.9%) were older (70±14 years vs 65±13 years; p<0.001), had a higher prevalence of cardiac comorbidities and a lower revascularisation rate compared with males. The primary outcome occurred in 12 934 patients (5.4%), at a 49% higher rate in females (6.8% vs 4.6% in males, p<0.001), which was attenuated to a 19% higher risk after multivariable adjustment. Findings were consistent across subgroups of age, AMI type and major risk factors. In the propensity-matched time-to-event analysis, female sex was associated with a 13% higher risk for 6-month HF readmission (6.4% vs 5.8% in males; HR 1.13, 95% CI 1.05 to 1.21, p<0.001), and the increased risk was evident early on after the AMI. Fatal HF rate was similar between groups (4.7% vs 4.6%, p=0.936), but females had a higher rate of the composite HF outcome (36.2% vs 27.5%, p<0.001).
Conclusion
In a large all-comers AMI survivors\' cohort, females had a higher HF hospitalisation risk that persisted after adjustment for baseline risk differences. This was consistent across several clinically relevant subgroups and was evident early on after the AMI.

© Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.

Heart: 29 Sep 2021; 107:1657-1663
Yandrapalli S, Malik A, Pemmasani G, Aronow W, ... Frishman W, Panza J
Heart: 29 Sep 2021; 107:1657-1663 | PMID: 33431424
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Impact:
Abstract

Risk of out-of-hospital cardiac arrest in patients with bipolar disorder or schizophrenia.

Barcella CA, Mohr G, Kragholm K, Christensen D, ... Gislason GH, Bach Søndergaard K
Objective
Patients with bipolar disorder and schizophrenia are at high cardiovascular risk; yet, the risk of out-of-hospital cardiac arrest (OHCA) compared with the general population remains scarcely investigated.
Methods
We conducted a nested case-control study using Cox regression to assess the association of bipolar disorder and schizophrenia with the HRs of OHCA of presumed cardiac cause (2001-2015). Reported are the HRs with 95% CIs overall and in subgroups defined by established cardiac disease, cardiovascular risk factors and psychotropic drugs.
Results
We included 35 017 OHCA cases and 175 085 age-matched and sex-matched controls (median age 72 years and 66.9% male). Patients with bipolar disorder or schizophrenia had overall higher rates of OHCA compared with the general population: HR 2.74 (95% CI 2.41 to 3.13) and 4.49 (95% CI 4.00 to 5.10), respectively. The association persisted in patients with both cardiac disease and cardiovascular risk factors at baseline (bipolar disorder HR 2.14 (95% CI 1.72 to 2.66), schizophrenia 2.84 (95% CI 2.20 to 3.67)) and among patients without known risk factors (bipolar disorder HR 2.14 (95% CI 1.09 to 4.21), schizophrenia HR 5.16 (95% CI 3.17 to 8.39)). The results were confirmed in subanalyses only including OHCAs presenting with shockable rhythm or receiving an autopsy. Antipsychotics-but not antidepressants, lithium or antiepileptics (the last two only tested in bipolar disorder)-increased OHCA hazard compared with no use in both disorders.
Conclusions
Patients with bipolar disorder or schizophrenia have a higher rate of OHCA compared with the general population. Cardiac disease, cardiovascular risk factors and antipsychotics represent important underlying mechanisms.

© Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.

Heart: 29 Sep 2021; 107:1544-1551
Barcella CA, Mohr G, Kragholm K, Christensen D, ... Gislason GH, Bach Søndergaard K
Heart: 29 Sep 2021; 107:1544-1551 | PMID: 33452118
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Impact:
Abstract

Fried-food consumption and risk of cardiovascular disease and all-cause mortality: a meta-analysis of observational studies.

Qin P, Zhang M, Han M, Liu D, ... Hu D, Hu F
Objective
We performed a meta-analysis, including dose-response analysis, to quantitatively determine the association of fried-food consumption and risk of cardiovascular disease and all-cause mortality in the general adult population.
Methods
We searched PubMed, EMBASE and Web of Science for all articles before 11 April 2020. Random-effects models were used to estimate the summary relative risks (RRs) and 95% CIs.
Results
In comparing the highest with lowest fried-food intake, summary RRs (95% CIs) were 1.28 (1.15 to 1.43; n=17, I2=82.0%) for major cardiovascular events (prospective: 1.24 (1.12 to 1.38), n=13, I2=75.7%; case-control: 1.91 (1.15 to 3.17), n=4, I2=92.1%); 1.22 (1.07 to 1.40; n=11, I2=77.9%) for coronary heart disease (prospective: 1.16 (1.05 to 1.29), n=8, I2=44.6%; case-control: 1.91 (1.05 to 3.47), n=3, I2=93.9%); 1.37 (0.97 to 1.94; n=4, I2=80.7%) for stroke (cohort: 1.21 (0.87 to 1.69), n=3, I2=77.3%; case-control: 2.01 (1.27 to 3.19), n=1); 1.37 (1.07 to 1.75; n=4, I2=80.0%) for heart failure; 1.02 (0.93 to 1.14; n=3, I2=27.3%) for cardiovascular mortality; and 1.03 (95% CI 0.96 to 1.12; n=6, I2=38.0%) for all-cause mortality. The association was linear for major cardiovascular events, coronary heart disease and heart failure.
Conclusions
Fried-food consumption may increase the risk of cardiovascular disease and presents a linear dose-response relation. However, the high heterogeneity and potential recall and misclassification biases for fried-food consumption from the original studies should be considered.

© Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.

Heart: 29 Sep 2021; 107:1567-1575
Qin P, Zhang M, Han M, Liu D, ... Hu D, Hu F
Heart: 29 Sep 2021; 107:1567-1575 | PMID: 33468573
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Impact:
Abstract

Vaping and cardiac disease.

Shahandeh N, Chowdhary H, Middlekauff HR
Tobacco cigarette smoking is the most prevalent reversible risk factor for cardiovascular disease in the USA. Electronic cigarettes, invented as an alternative nicotine source for smokers unable or unwilling to stop smoking, have gained skyrocketing popularity, but their cardiovascular risk remains uncertain. Although data recently analysed in a Cochran report do support their superior effectiveness to other forms of nicotine replacement therapies for smoking cessation, electronic cigarettes are also frequently used by non-smokers-especially high school students. There are no long-term outcome studies on the cardiovascular risk of vaping electronic cigarettes, but the effects of electronic cigarettes on known risk factors for cardiovascular disease, including neurohumoural activation, oxidative stress and inflammation, endothelial function and thrombosis, have been studied. In this review, we summarise evidence in humans that supports the notion that while electronic cigarettes may be less harmful than traditional cigarettes, they are not harmless. Additionally, the increasing popularity of vaping marijuana with its unknown cardiovascular risks as well as the outbreak in 2019 of EVALI (electronic cigarette, or vaping, product use-associated lung injury) related to bootlegged vaping products raise further concerns. Before physicians can confidently advise their smoking patients about the role of electronic cigarettes as a means of smoking cessation to lower cardiovascular risk, improved regulation and quality control is necessary.

© Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.

Heart: 29 Sep 2021; 107:1530-1535
Shahandeh N, Chowdhary H, Middlekauff HR
Heart: 29 Sep 2021; 107:1530-1535 | PMID: 33574049
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Impact:
Abstract

Aortitis: recent advances, current concepts and future possibilities.

Pugh D, Grayson P, Basu N, Dhaun N
Broadly defined, aortitis refers to inflammation of the aorta and incorporates both infectious and non-infectious aetiologies. As advanced imaging modalities are increasingly incorporated into clinical practice, the phenotypic spectrum associated with aortitis has widened. The primary large vessel vasculitides, giant cell arteritis and Takayasu arteritis, are the most common causes of non-infectious aortitis. Aortitis without systemic disease or involvement of other vascular territories is classified as clinically isolated aortitis. Periaortitis, where inflammation spreads beyond the aortic wall, is an important disease subset with a distinct group of aetiologies. Infectious aortitis can involve bacterial, viral or fungal pathogens and, while uncommon, can be devastating. Importantly, optimal management strategies and patient outcomes differ between aortitis subgroups highlighting the need for a thorough diagnostic workup. Monitoring disease activity over time is also challenging as normal inflammatory markers do not exclude significant vascular inflammation, particularly after starting treatment. Additional areas of unmet clinical need include clear disease classifications and improved short-term and long-term management strategies. Some of these calls are now being answered, particularly with regard to large vessel vasculitis where our understanding has advanced significantly in recent years. Work extrapolated from temporal artery histology has paved the way for targeted biological agents and, although glucocorticoids remain central to the management of non-infectious aortitis, these may allow reduced glucocorticoid reliance. Future work should seek to clarify disease definitions, improve diagnostic pathways and ultimately allow a more stratified approach to patient management.

© Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.

Heart: 29 Sep 2021; 107:1620-1629
Pugh D, Grayson P, Basu N, Dhaun N
Heart: 29 Sep 2021; 107:1620-1629 | PMID: 33593995
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Impact:
Abstract

Management considerations in the adult with surgically modified d-transposition of the great arteries.

Gaur L, Cedars A, Diller GP, Kutty S, Orwat S
Dextro-transposition of the great arteries (D-TGA) has undergone a significant evolution in surgical repair, leading to survivors with vastly different postsurgical anatomy which in turn guides their long-term cardiovascular morbidity and mortality. Atrial switch repair survivors are limited by a right ventricle in the systemic position, arrhythmia and atrial baffles prone to obstruction or leak. Functional assessment of the systemic right ventricle is complex, requiring multimodality imaging to include specialised echocardiography and cross-sectional imaging (MRI and CT). In the current era, most neonates undergo the arterial switch operation with increasing understanding of near-term and long-term outcomes specific to their cardiac anatomy. Long-term observations of the Lecompte manoeuvre or coronary stenoses following transfer continue, with evolving understanding to improve surveillance. Ultimately, an understanding of postsurgical anatomy, specialised imaging techniques and interventional and electrophysiological procedures is essential to comprehensive care of D-TGA survivors.

© Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.

Heart: 29 Sep 2021; 107:1613-1619
Gaur L, Cedars A, Diller GP, Kutty S, Orwat S
Heart: 29 Sep 2021; 107:1613-1619 | PMID: 33741578
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Impact:
Abstract

Intensive low-density lipoprotein cholesterol lowering in cardiovascular disease prevention: opportunities and challenges.

Packard C, Chapman MJ, Sibartie M, Laufs U, Masana L
Elevated levels of low-density lipoprotein cholesterol (LDL-C) are associated with increased risk of coronary heart disease and stroke. Guidelines for the management of dyslipidaemia from the European Society of Cardiology (ESC) and the European Atherosclerosis Society (EAS) were updated in late 2019 in light of recent intervention trials involving the use of innovative lipid-lowering agents in combination with statins. The new guidelines advocate achieving very low LDL-C levels in individuals at highest risk, within the paradigm of \'lower is better\'. With the advent of combination therapy using ezetimibe and/or proprotein convertase subtilisin/kexin type 9 inhibitors in addition to statins, the routine attainment of extremely low LDL-C levels in the clinic has become a reality. Moreover, clinical trials in this setting have shown that, over the 5-7 years of treatment experience to date, profound LDL-C lowering leads to further reduction in cardiovascular events compared with more moderate lipid lowering, with no associated safety concerns. These reassuring findings are bolstered by genetic studies showing lifelong very low LDL-C levels (<1.4 mmol/L; <55 mg/dL) are associated with lower cardiovascular risk than in the general population, with no known detrimental health effects. Nevertheless, long-term safety studies are required to consolidate the present evidence base. This review summarises key data supporting the ESC/EAS recommendation to reduce markedly LDL-C levels, with aggressive goals for LDL-C in patients at highest risk, and provides expert opinion on its significance for clinical practice.

© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

Heart: 29 Sep 2021; 107:1369-1375
Packard C, Chapman MJ, Sibartie M, Laufs U, Masana L
Heart: 29 Sep 2021; 107:1369-1375 | PMID: 33795379
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Impact:
Abstract

Lipoprotein(a) is robustly associated with aortic valve calcium.

Kaiser Y, Singh SS, Zheng KH, Verbeek R, ... Stroes ESG, Bos D
Objectives
To investigate the prevalence and quantity of aortic valve calcium (AVC) in two large cohorts, stratified according to age and lipoprotein(a) (Lp(a)), and to assess the association between Lp(a) and AVC.
Methods
We included 2412 participants from the population-based Rotterdam Study (52% women, mean age=69.6±6.3 years) and 859 apparently healthy individuals from the Amsterdam University Medical Centers (UMC) outpatient clinic (57% women, mean age=45.9±11.6 years). All individuals underwent blood sampling to determine Lp(a) concentration and non-enhanced cardiac CT to assess AVC. Logistic and linear regression analyses were performed to investigate the associations of Lp(a) with the presence and amount of AVC.
Results
The prevalence of AVC was 33.1% in the Rotterdam Study and 5.4% in the Amsterdam UMC cohort. Higher Lp(a) concentrations were independently associated with presence of AVC in both cohorts (OR per 50 mg/dL increase in Lp(a): 1.54 (95% CI 1.36 to 1.75) in the Rotterdam Study cohort and 2.02 (95% CI 1.19 to 3.44) in the Amsterdam UMC cohort). In the Rotterdam Study cohort, higher Lp(a) concentrations were also associated with increase in aortic valve Agatston score (β 0.19, 95% CI 0.06 to 0.32 per 50 mg/dL increase).
Conclusions
Lp(a) is robustly associated with presence of AVC in a wide age range of individuals. These results provide further rationale to assess the effect of Lp(a) lowering interventions in individuals with early AVC to prevent end-stage aortic valve stenosis.

© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

Heart: 29 Sep 2021; 107:1422-1428
Kaiser Y, Singh SS, Zheng KH, Verbeek R, ... Stroes ESG, Bos D
Heart: 29 Sep 2021; 107:1422-1428 | PMID: 33963048
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Impact:
Abstract

Risks and benefits of percutaneous coronary intervention in spontaneous coronary artery dissection.

Kotecha D, Garcia-Guimaraes M, Premawardhana D, Pellegrini D, ... Alfonso F, Adlam D
Objective
To investigate percutaneous coronary intervention (PCI) practice in an international cohort of patients with spontaneous coronary artery dissection (SCAD). To explore factors associated with complications and study angiographic and longer term outcomes.
Methods
SCAD patients (n=215, 94% female) who underwent PCI from three national cohort studies were investigated and compared with a matched cohort of conservatively managed SCAD patients (n=221).
Results
SCAD-PCI patients were high risk at presentation with only 8.8% undergoing PCI outside the context of ST-elevation myocardial infarction/cardiac arrest, thrombolysis in myocardial infarction (TIMI) 0/1 flow or proximal dissections. PCI complications occurred in 38.6% (83/215), with 13.0% (28/215) serious complications. PCI-related complications were associated with more extensive dissections (multiple vs single American Heart Association coronary segments, OR 1.9 (95% CI: 1.06-3.39),p=0.030), more proximal dissections (proximal diameter per mm, OR 2.25 (1.38-3.67), p=0.001) and dissections with no contrast penetration of the false lumen (Yip-Saw 2 versus 1, OR 2.89 (1.12-7.43), p=0.028). SCAD-PCI involved long lengths of stent (median 46mm, IQR: 29-61mm). Despite these risks, SCAD-PCI led to angiographic improvements in those with reduced TIMI flow in 84.3% (118/140). Worsening TIMI flow was only seen in 7.0% (15/215) of SCAD-PCI patients. Post-PCI major adverse cardiovascular and cerebrovascular events (MACCE) and left ventricular function outcomes were favourable.
Conclusion
While a conservative approach to revascularisation is favoured, SCAD cases with higher risk presentations may require PCI. SCAD-PCI is associated with longer stent lengths and a higher risk of complications but leads to overall improvements in coronary flow and good medium-term outcomes in patients.

© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY. Published by BMJ.

Heart: 29 Sep 2021; 107:1398-1406
Kotecha D, Garcia-Guimaraes M, Premawardhana D, Pellegrini D, ... Alfonso F, Adlam D
Heart: 29 Sep 2021; 107:1398-1406 | PMID: 34006503
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Impact:
Abstract

Lipoprotein(a) has no major impact on calcification activity in patients with mild to moderate aortic valve stenosis.

Kaiser Y, Nurmohamed NS, Kroon J, Verberne HJ, ... Zheng KH, Boekholdt SM
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.

© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY. Published by BMJ.

Heart: 29 Sep 2021; epub ahead of print
Kaiser Y, Nurmohamed NS, Kroon J, Verberne HJ, ... Zheng KH, Boekholdt SM
Heart: 29 Sep 2021; epub ahead of print | PMID: 34593533
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Impact:
Abstract

Weight management and determinants of weight change in patients with coronary artery disease.

Tijssen A, Snaterse M, Minneboo M, Lachman S, ... Peters RJ, Jørstad HT
Objective
To study the effects of a comprehensive secondary prevention programme on weight loss and to identify determinants of weight change in patients with coronary artery disease (CAD).
Methods
We performed a secondary analysis focusing on the subgroup of overweight CAD patients (BMI ≥27 kg/m2) in the Randomised Evaluation of Secondary Prevention by Outpatient Nurse SpEcialists-2 (RESPONSE-2) multicentre randomised trial. We evaluated weight change from baseline to 12-month follow-up; multivariable logistic regression with backward elimination was used to identify determinants of weight change.
Results
Intervention patients (n=280) lost significantly more weight than control patients (n=257) (-2.4±7.1 kg vs -0.2±4.6 kg; p<0.001). Individual weight change varied widely, with weight gain (≥1.0 kg) occurring in 36% of interventions versus 41% controls (p=0.21). In the intervention group, weight loss of ≥5% was associated with higher age (OR 2.94), lower educational level (OR 1.91), non-smoking status (OR 2.92), motivation to start with weight loss directly after the baseline visit (OR 2.31) and weight loss programme participation (OR 3.33), whereas weight gain (≥1 kg) was associated with smoking cessation ≤6 months before or during hospitalisation (OR 3.21), non-Caucasian ethnicity (OR 2.77), smoking at baseline (OR 2.70), lower age (<65 years) (OR 1.47) and weight loss programme participation (OR 0.59).
Conclusion
The comprehensive secondary prevention programme was, on average, effective in achieving weight loss. However, wide variation was observed. As weight gain was observed in over one in three participants in both groups, prevention of weight gain may be as important as attempts to lose weight.
Trial registration number
NTR3937.

© Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.

Heart: 29 Sep 2021; 107:1552-1559
Tijssen A, Snaterse M, Minneboo M, Lachman S, ... Peters RJ, Jørstad HT
Heart: 29 Sep 2021; 107:1552-1559 | PMID: 34326136
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Impact:
Abstract

Catheter ablation as first-line treatment for paroxysmal atrial fibrillation: a systematic review and meta-analysis.

Imberti JF, Ding WY, Kotalczyk A, Zhang J, ... Andrade J, Gupta D
Objective
To assess the efficacy and safety of catheter ablation (CA) compared with antiarrhythmic drugs (AADs) as first-line treatment for symptomatic paroxysmal atrial fibrillation (AF).
Methods
Systematic review and meta-analysis of randomised controlled trials identified using MEDLINE, Cochrane Library and Embase published between 01/01/2000 and 19/03/2021. The primary efficacy endpoint was the first documented recurrence of atrial arrhythmias following the blanking period. The primary safety endpoint was a composite of all serious adverse events (SAEs).
Results
From 441 records, 6 studies met the inclusion criteria. 609 patients received CA, while 603 received AAD therapy. 212/609 patients in the CA group had a recurrence of atrial arrhythmias as compared with 318/603 in the AADs group resulting in a 36% relative risk reduction (risk ratio: 0.64, 95% CI 0.51 to 0.80, p<0.01). The risk of all SAEs was not statistically different between CA and AAD (0.87, 0.58 to 1.30, p=0.49); 107/609 SAE in the CA group vs 126/603 in the AAD group. Both recurrence of symptomatic atrial arrhythmias (109/505 vs 186/504) and healthcare utilisation (126/397 vs 185/394) were significantly lower in the CA group (0.53, 0.35 to 0.79 and 0.65, 0.48 to 0.89, respectively). There was a 79% reduction in the crossover rate during follow-up among patients randomised to CA compared with AAD (0.21, 0.13 to 0.32, p<0.01).
Conclusions
First-line treatment with CA is superior to AAD therapy in patients with symptomatic paroxysmal AF, as it significantly reduces the recurrence of any atrial arrhythmias and symptomatic atrial arrhythmias, and healthcare resource utilisation with comparable safety profile.

© Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.

Heart: 29 Sep 2021; 107:1630-1636
Imberti JF, Ding WY, Kotalczyk A, Zhang J, ... Andrade J, Gupta D
Heart: 29 Sep 2021; 107:1630-1636 | PMID: 34261737
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Impact:
Abstract

Clinical significance of pulmonary hypertension in patients with constrictive pericarditis.

Lim K, Yang JH, Miranda WR, Chang SA, ... Greason KL, Oh JK
Objectives
We investigated haemodynamics and clinical outcomes according to type of pulmonary hypertension (PH) in patients with constrictive pericarditis (CP).
Background
As the prevalence of CP with concomitant myocardial disease (mixed CP) grows, PH is more commonly seen in patients with CP. However, haemodynamic and outcome data according to the presence or absence of PH are limited.
Methods
150 patients with surgically confirmed CP who underwent echocardiography and cardiac catheterisation within 7 days at two tertiary centres were divided into three groups: no-PH, isolated postcapillary PH (Ipc-PH) and combined postcapillary and precapillary PH (Cpc-PH). Primary outcome was all-cause mortality during follow-up.
Result
In this retrospective cohort study, 110 (73.3%) had PH (mean pulmonary artery pressure ≥25 mm Hg). Cpc-PH, using defined cut-offs for pulmonary vascular resistance (>3 Wood units) or diastolic pulmonary gradient (≥7 mm Hg), was seen in 18 patients (12%). The Cpc-PH group had a higher prevalence of comorbidities (diabetes and atrial fibrillation) and concomitant myocardial disease as an aetiology of CP than other groups. Pulmonary vascular resistance had a significant direct correlation with medial E/e\' by Doppler echocardiography (r=0.404, p<0.001). Survival rate was significantly lower in the Cpc-PH than the no-PH (p=0.002) and Ipc-PH (p=0.024) groups. On multivariable analysis, age, New York Heart Association functional class IV, medial e\' velocity, Cpc-PH and Ipc-PH were independently associated with long-term mortality.
Conclusion
Combined postcapillary and precapillary PH develops in a subset of patients with CP and is associated with long-term mortality after pericardiectomy.

© Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.

Heart: 29 Sep 2021; 107:1651-1656
Lim K, Yang JH, Miranda WR, Chang SA, ... Greason KL, Oh JK
Heart: 29 Sep 2021; 107:1651-1656 | PMID: 34285103
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Impact:
Abstract

Education on cardiac risk and CPR in cardiology clinic waiting rooms: a randomised clinical trial.

McIntyre D, Thiagalingam A, Klimis H, Von Huben A, Marschner S, Chow CK
Objective
Waiting time is inevitable during cardiovascular (CV) care. This study examines whether waiting room-based CV education could complement CV care.
Methods
A 2:1 randomised clinical trial of patients in waiting rooms of hospital cardiology clinics. Intervention participants received a series of tablet-delivered CV educational videos and were randomised 1:1 to receive another video on cardiopulmonary resuscitation (CPR) or no extra video. Control received usual care. The primary outcome was the proportion of participants reporting high motivation to improve CV risk-modifying behaviours (physical activity, diet and blood pressure monitoring) post-clinic.
Secondary outcomes
clinic satisfaction, CV lifestyle risk factors (RFs) and confidence to perform CPR. Assessors were blinded to treatment allocation.
Results
Among 514 screened, 330 were randomised (n=220 intervention, n=110 control) between December 2018 and March 2020, mean age 53.8 (SD 15.2), 55.2% male. Post-clinic, more intervention participants reported high motivation to improve CV risk-modifying behaviours: 29.6% (64/216) versus 18.7% (20/107), relative risk (RR) 1.63 (95% CI 1.04 to 2.55). Intervention participants reported higher clinic satisfaction RR: 2.19 (95% CI 1.45 to 3.33). Participants that received the CPR video (n=110) reported greater confidence to perform CPR, RR 1.61 (95% CI 1.20 to 2.16). Overall, the proportion of participants reporting optimal CV RFs increased between baseline and 30-day follow-up (16.1% vs 24.8%, OR=2.44 (95% CI 1.38 to 4.49)), but there was no significant between-group difference at 30 days.
Conclusion
CV education delivery in the waiting room is a scalable concept and may be beneficial to CV care. Larger studies could explore its impact on clinical outcomes.
Trial registration number
ANZCTR12618001725257.

© Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.

Heart: 29 Sep 2021; 107:1637-1643
McIntyre D, Thiagalingam A, Klimis H, Von Huben A, Marschner S, Chow CK
Heart: 29 Sep 2021; 107:1637-1643 | PMID: 34290036
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Impact:
Abstract

Ventricular and atrial function and deformation is largely preserved after arterial switch operation.

Schuwerk R, Freitag-Wolf S, Krupickova S, Gabbert DD, ... Langguth P, Voges I
Objective
To test the hypothesis that ventricular and atrial function are different between patients with transposition of the great arteries (TGA) after arterial switch operation (ASO) and healthy controls.
Methods
103 consecutive patients with TGA (median age: 16.7 years, 4.3-39.6 years, 71.8% male) were compared with 77 controls (median age: 15.4 years, 6.3-43.2 years, 66.2% male). Biventricular and biatrial function were assessed using standard cardiovascular magnetic resonance (CMR) techniques and feature tracking. Group comparison was performed with conventional non-parametrical statistics and machine learning methods to find the variables most discriminative between patients and controls. These variables were used to build a multivariable logistic regression model to assess the case-control status.
Results
Markers of left and right ventricular function (LV; RV) (ejection fraction, MAPSE, TAPSE, LV long-axis strain) as well as LV global longitudinal (-20.7 (-24.1; -17.9) vs -23.7 (-26.1; -21.6), p<0.001), circumferential (-29.4 (-32.2; -26.5) vs -30.5 (-33.6; 29), p=0.001) and atrial longitudinal strain (left atrium (LA): 23.3 (18.6; 28.8) vs 36.7 (30.7; 44), p<0001; right atrium: 21.7 (18.2; 27.8) vs 34.9 (26.9; 40.3), p<0.001) were reduced in patients compared with controls using non-parametrical testing. The logistic regression model including the most discriminative variables from univariate and machine learning analysis demonstrated significant differences between patients and controls only for TAPSE and LA global longitudinal strain.
Conclusions
Biventricular and biatrial function are largely preserved after ASO for TGA. Using a comprehensive CMR protocol along with statistical machine learning methods and a regression approach, only RV longitudinal function and LA function are significantly impaired.

© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

Heart: 29 Sep 2021; 107:1644-1650
Schuwerk R, Freitag-Wolf S, Krupickova S, Gabbert DD, ... Langguth P, Voges I
Heart: 29 Sep 2021; 107:1644-1650 | PMID: 34349009
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Impact:
Abstract

Cross-sectional study of aortic valve calcification and cardiovascular risk factors in older Danish men.

Khurrami L, Møller JE, Lindholt JS, Urbonaviciene G, ... Fredgart MH, Diederichsen ACP
Objective
Aortic valve calcification (AVC) and coronary artery calcification (CAC) are predictors of cardiovascular disease (CVD), presumably sharing risk factors. Our objectives were to determine the prevalence and extent of AVC in a large population of men aged 60-74 years and to assess the association between AVC and cardiovascular risk factors including CAC and biomarkers.
Methods
Participants from the DANish CArdioVAscular Screening and intervention trial (DANCAVAS) with AVC and CAC scores and without previous valve replacement were included in the study. Calcification scores were calculated on non-contrast CT scans. Cardiovascular risk factors were self-reported, measured or both, and further explored using descriptive and regression analysis for AVC association.
Results
14 073 men aged 60-74 years were included. The AVC scores ranged from 0 to 9067 AU, with a median AVC of 6 AU (IQR 0-82). In 8156 individuals (58.0%), the AVC score was >0 and 215 (1.5%) had an AVC score ≥1200. In the regression analysis, all cardiovascular risk factors were associated with AVC; however, after inclusion of CAC ≥400, only age (ratio of expected counts (REC) 1.07 (95% CI 1.06 to 1.09)), hypertension (REC 1.24 (95% CI 1.09 to 1.41)), obesity (REC 1.34 (95% CI 1.20 to 1.50)), known CVD (REC 1.16 (95% CI 1.03 to 1.31)) and serum phosphate (REC 2.25 (95% CI 1.66 to 3.10) remained significantly associated, while smoking, diabetes, hyperlipidaemia, estimated glomerular filtration rate and serum calcium were not.
Conclusions
AVC was prevalent in the general population of men aged 60-74 years and was significantly associated with all modifiable cardiovascular risk factors, but only selectively after adjustment for CAC ≥400 AU.
Trial registration number
NCT03946410 and ISRCTN12157806.

© Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.

Heart: 29 Sep 2021; 107:1536-1543
Khurrami L, Møller JE, Lindholt JS, Urbonaviciene G, ... Fredgart MH, Diederichsen ACP
Heart: 29 Sep 2021; 107:1536-1543 | PMID: 34376488
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Impact:
Abstract

Novel bleeding prediction model in atrial fibrillation patients on new oral anticoagulants.

Barnett-Griness O, Stein N, Kotler A, Saliba W, Gronich N
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.

© Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.

Heart: 20 Sep 2021; epub ahead of print
Barnett-Griness O, Stein N, Kotler A, Saliba W, Gronich N
Heart: 20 Sep 2021; epub ahead of print | PMID: 34548336
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Impact:
Abstract

Prognostic value of admission high-sensitivity troponin in patients with ST-elevation myocardial infarction.

Coelho-Lima J, Georgiopoulos G, Ahmed J, Adil SER, ... Stamatelopoulos K, Spyridopoulos I
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.

© Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.

Heart: 19 Sep 2021; epub ahead of print
Coelho-Lima J, Georgiopoulos G, Ahmed J, Adil SER, ... Stamatelopoulos K, Spyridopoulos I
Heart: 19 Sep 2021; epub ahead of print | PMID: 34544804
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Impact:
Abstract

Late complication rates after aortic coarctation repair in patients with or without a bicuspid aortic valve.

Lim MS, Cordina R, Kotchetkova I, Celermajer DS
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.

© Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.

Heart: 16 Sep 2021; epub ahead of print
Lim MS, Cordina R, Kotchetkova I, Celermajer DS
Heart: 16 Sep 2021; epub ahead of print | PMID: 34535439
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Impact:
Abstract

Early percutaneous mitral commissurotomy or conventional management for asymptomatic mitral stenosis: a randomised clinical trial.

Kang DH, Park SJ, Lee SA, Lee S, ... Park SW, Park SJ
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.

© Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.

Heart: 14 Sep 2021; epub ahead of print
Kang DH, Park SJ, Lee SA, Lee S, ... Park SW, Park SJ
Heart: 14 Sep 2021; epub ahead of print | PMID: 34526318
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Impact:
Abstract

Case-finding and genetic testing for familial hypercholesterolaemia in primary care.

Qureshi N, Akyea RK, Dutton B, Humphries SE, ... Kai J, FAMCAT study
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.

© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY. Published by BMJ.

Heart: 13 Sep 2021; epub ahead of print
Qureshi N, Akyea RK, Dutton B, Humphries SE, ... Kai J, FAMCAT study
Heart: 13 Sep 2021; epub ahead of print | PMID: 34521694
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Impact:
Abstract

Association of carbohydrate and saturated fat intake with cardiovascular disease and mortality in Australian women.

Gribbin S, Enticott J, Hodge AM, Moran L, ... Joham A, Zaman S
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.

© Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.

Heart: 10 Sep 2021; epub ahead of print
Gribbin S, Enticott J, Hodge AM, Moran L, ... Joham A, Zaman S
Heart: 10 Sep 2021; epub ahead of print | PMID: 34509998
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Impact:
Abstract

Hydration for prevention of kidney injury after primary coronary intervention for acute myocardial infarction: a randomised clinical trial.

Liu Y, Tan N, Huo Y, Chen S, ... Xian Y, Chen J
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.

© Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.

Heart: 10 Sep 2021; epub ahead of print
Liu Y, Tan N, Huo Y, Chen S, ... Xian Y, Chen J
Heart: 10 Sep 2021; epub ahead of print | PMID: 34509996
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Impact:
Abstract

Prognostic impact of cardiac surgery in left-sided infective endocarditis according to risk profile.

Garcia Granja PE, Lopez J, Vilacosta I, Saéz C, ... Carrasco-Moraleja M, San Román JA
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.

© Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.

Heart: 10 Sep 2021; epub ahead of print
Garcia Granja PE, Lopez J, Vilacosta I, Saéz C, ... Carrasco-Moraleja M, San Román JA
Heart: 10 Sep 2021; epub ahead of print | PMID: 34509995
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Abstract

Impact of afterload and infiltration on coexisting aortic stenosis and transthyretin amyloidosis.

Patel KP, Scully PR, Nitsche C, Kammerlander AA, ... Mascherbauer J, Moon JC
Objective
The coexistence of wild-type transthyretin cardiac amyloidosis (ATTR) is common in patients with severe aortic stenosis (AS) undergoing transcatheter aortic valve implantation (TAVI). However, the impact of ATTR and AS on the resultant AS-ATTR is unclear and poses diagnostic and management challenges. We therefore used a multicohort approach to evaluate myocardial structure, function, stress and damage by assessing age-related, afterload-related and amyloid-related remodelling on the resultant AS-ATTR phenotype.
Methods
We compared four samples (n=583): 359 patients with AS, 107 with ATTR (97% Perugini grade 2), 36 with AS-ATTR (92% Perugini grade 2) and 81 age-matched and ethnicity-matched controls. 99mTc-3,3-diphosphono-1,2-propanodicarboxylic acid (DPD) scintigraphy was used to diagnose amyloidosis (Perugini grade 1 was excluded). The primary end-point was NT-pro Brain Natriuretic Peptide (BNP) and secondary end-points related to myocardial structure, function and damage.
Results
Compared with older age controls, the three disease cohorts had greater cardiac remodelling, worse function and elevated NT-proBNP/high-sensitivity Troponin-T (hsTnT). NT-proBNP was higher in AS-ATTR (2844 (1745, 4635) ng/dL) compared with AS (1294 (1077, 1554)ng/dL; p=0.002) and not significantly different to ATTR (3272 (2552, 4197) ng/dL; p=0.63). Diastology, hsTnT and prevalence of carpal tunnel syndrome were statistically similar between AS-ATTR and ATTR and higher than AS. The left ventricular mass indexed in AS-ATTR was lower than ATTR (139 (112, 167) in AS-ATTR was lower than ATTR (139 (112, 167) in AS-ATTR was lower than ATTR (139 (112, 167) vs 180 (167, 194) g; p=0.013) and non-significantly different to AS (120 (109, 130) g; p=0.179).
Conclusions
The AS-ATTR phenotype likely reflects an early stage of amyloid infiltration, but the combined insult resembles ATTR. Even after treatment of AS, ATTR-specific therapy is therefore likely to be beneficial.

© Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.

Heart: 07 Sep 2021; epub ahead of print
Patel KP, Scully PR, Nitsche C, Kammerlander AA, ... Mascherbauer J, Moon JC
Heart: 07 Sep 2021; epub ahead of print | PMID: 34497140
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Abstract

Premature ventricular complexes and development of heart failure in a community-based population.

Limpitikul WB, Dewland TA, Vittinghoff E, Soliman E, ... Hempfling R, Marcus GM
Objective
A higher premature ventricular complex (PVC) frequency is associated with incident congestive heart failure (CHF) and death. While certain PVC characteristics may contribute to that risk, the current literature stems from patients in medical settings and is therefore prone to referral bias. This study aims to identify PVC characteristics associated with incident CHF in a community-based setting.
Methods
The Cardiovascular Health Study is a cohort of community-dwelling individuals who underwent prospective evaluation and follow-up. We analysed 24-hour Holter data to assess PVC characteristics and used multivariable logistic and Cox proportional hazards models to identify predictors of a left ventricular ejection fraction (LVEF) decline and incident CHF, respectively.
Results
Of 871 analysed participants, 316 participants exhibited at least 10 PVCs during the 24-hour recording. For participants with PVCs, the average age was 72±5 years, 41% were women and 93% were white. Over a median follow-up of 11 years, 34% developed CHF. After adjusting for demographics, cardiovascular comorbidities, antiarrhythmic drug use and PVC frequency, a greater heterogeneity of the PVC coupling interval was associated with an increased risk of LVEF decline and incident CHF. Of note, neither PVC duration nor coupling interval duration exhibited a statistically significant relationship with either outcome.
Conclusions
In this first community-based study to identify Holter-based features of PVCs that are associated with LVEF reduction and incident CHF, the fact that coupling interval heterogeneity was an independent risk factor suggests that the mechanism of PVC generation may influence the risk of heart failure.

© Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.

Heart: 06 Sep 2021; epub ahead of print
Limpitikul WB, Dewland TA, Vittinghoff E, Soliman E, ... Hempfling R, Marcus GM
Heart: 06 Sep 2021; epub ahead of print | PMID: 34493549
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Impact:
Abstract

Cardiac myxomas: clinical presentation, diagnosis and management.

Griborio-Guzman AG, Aseyev OI, Shah H, Sadreddini M
Cardiac myxomas (CM) are the most common type of primary cardiac tumours in adults, which have an approximate incidence of up to 0.2% in some autopsy series. The purpose of this review is to summarise the literature on CM, including clinical presentation, differential diagnosis, work-up including imaging modalities and histopathology, management, and prognosis. CM are benign neoplasms developed from multipotent mesenchyme and usually present as an undifferentiated atrial mass. They are typically pedunculated and attached at the fossa ovalis, on the left side of the atrial septum. Potentially life-threatening, the presence of CM calls for prompt diagnosis and surgical resection. Infrequently asymptomatic, patients with CM exhibit various manifestations, ranging from influenza-like symptoms, heart failure and stroke, to sudden death. Although non-specific, a classic triad for CM involves constitutional, embolic, and obstructive or cardiac symptoms. CM may be purposefully characterised or incidentally diagnosed on an echocardiogram, CT scan or cardiac MRI, all of which can help to differentiate CM from other differentials. Echocardiogram is the first-line imaging technique; however, it is fallible, potentially resulting in uncommonly situated CM being overlooked. The diagnosis of CM can often be established based on clinical, imaging and histopathology features. Definitive diagnosis requires macroscopic and histopathological assessment, including positivity for endothelial cell markers such as CD31 and CD34. Their prognosis is excellent when treated with prompt surgical resection, with postsurgical survival rates analogous to overall survival in the age-matched general population.

© Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.

Heart: 06 Sep 2021; epub ahead of print
Griborio-Guzman AG, Aseyev OI, Shah H, Sadreddini M
Heart: 06 Sep 2021; epub ahead of print | PMID: 34493547
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Abstract

Prognostic significance of longitudinal strain in dilated cardiomyopathy with recovered ejection fraction.

Merlo M, Masè M, Perry A, La Franca E, ... Sinagra G, Adamo L
Objective
Patients with non-ischaemic dilated cardiomyopathy (NICM) may experience a normalisation in left ventricular ejection fraction (LVEF). Although this correlates with improved prognosis, it does not correspond to a normalisation in the risk of death during follow-up. Currently, there are no tools to risk stratify this population. We tested the hypothesis that absolute global longitudinal strain (aGLS) is associated with mortality in patients with NICM and recovered ejection fraction (LVEF).
Methods
We designed a retrospective, international, longitudinal cohort study enrolling patients with NICM with LVEF <40% improved to the normal range (>50%). We studied the relationship between aGLS measured at the time of the first recording of a normalised LVEF and all-cause mortality during follow-up. We considered aGLS >18% as normal and aGLS ≥16% as of potential prognostic value.
Results
206 patients met inclusion criteria. Median age was 53.5 years (IQR 44.3-62.8) and 56.6% were males. LVEF at diagnosis was 32.0% (IQR 24.0-38.8). LVEF at the time of recovery was 55.0% (IQR 51.7-60.0). aGLS at the time of LVEF recovery was 13.6%±3.9%. 166 (80%) and 141 (68%) patients had aGLS ≤18% and <16%, respectively. During a follow-up of 5.5±2.8 years, 35 patients (17%) died. aGLS at the time of first recording of a recovered LVEF correlated with mortality during follow-up (HR 0.90, 95% CI 0.91 to 0.99, p=0.048 in adjusted Cox model). No deaths were observed in patients with normal aGLS (>18%). In unadjusted Kaplan-Meier survival analysis, aGLS <16% was associated with higher mortality during follow-up (31 deaths (22%) in patients with GLS <16% vs 4 deaths (6.2%) in patients with GLS ≥16%, HR 3.2, 95% CI 1.1 to 9, p=0.03).
Conclusions
In patients with NICM and normalised LVEF, an impaired aGLS at the time of LVEF recovery is frequent and associated with worse outcomes.

© Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.

Heart: 06 Sep 2021; epub ahead of print
Merlo M, Masè M, Perry A, La Franca E, ... Sinagra G, Adamo L
Heart: 06 Sep 2021; epub ahead of print | PMID: 34493546
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Abstract

Incidence, risk factors, natural history and outcomes of heart failure in patients with Graves\' disease.

Naser JA, Pislaru S, Stan MN, Lin G
Objective
Graves\' disease (GD) can both aggravate pre-existing cardiac disease and cause de novo heart failure (HF), but large-scale studies are lacking. We aimed to investigate the incidence, risk factors and outcomes of incident GD-related HF.
Methods
Patients with GD (2009-2019) were retrospectively included. HF with reduced ejection fraction (HFrEF) was defined by left ventricular ejection fraction <50% and Framingham criteria, while HF with preserved ejection fraction (HFpEF) was defined according to the HFA-PEFF criteria. HF due to ischaemia, valve disorder or other structural heart disease was excluded. Proportional hazards regression was used to analyse risk factors and outcomes.
Results
Of 1371 patients with GD, HF occurred in 74 (5.4%) patients (31 (2.3%) HFrEF; 43 (3.1%) HFpEF). In HFrEF, atrial fibrillation (AF) (HR 10.5 (3.0-37.3), p<0.001) and thyrotropin receptor antibody (TRAb) level (HR 1.05 (1.01-1.09) per unit, p=0.007) were independent risk factors. In HFpEF, the independent risk factors were chronic obstructive pulmonary disease (HR 7.2 (3.5-14.6), p<0.001), older age (HR 1.5 (1.2-2.0) per 10 years, p=0.001), overt hyperthyroidism (HR 6.4 (1.5-27.1), p=0.01), higher body mass index (BMI) (HR 1.07 (1.03-1.10) per unit, p=0.001) and hypertension (HR 3.1 (1.3-7.2), p=0.008). The risk of cardiovascular hospitalisations was higher in both HFrEF (HR 10.3 (5.5-19.4), p<0.001) and HFpEF (HR 6.7 (3.7-12.2), p<0.001). However, only HFrEF was associated with an increased risk of all-cause mortality (HR 5.17 (1.3-19.9), p=0.02) and ventricular tachycardia/fibrillation (HR 64.3 (15.9-259.7), p<0.001).
Conclusion
De novo HF occurs in 5.4% of patients with GD and is associated with increased risk of cardiovascular hospitalisations and mortality. Risk factors include AF, higher TRAb, higher BMI and overt hyperthyroidism.

© Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.

Heart: 05 Sep 2021; epub ahead of print
Naser JA, Pislaru S, Stan MN, Lin G
Heart: 05 Sep 2021; epub ahead of print | PMID: 34489313
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Abstract

Cardiac resynchronisation therapy in anthracycline-induced cardiomyopathy.

Patel D, Kumar A, Moennich LA, Trulock K, ... Wilkoff BL, Rickard J
Introduction
Chemotherapy-induced cardiomyopathy has been increasingly recognised as patients are living longer with more effective treatments for their malignancies. Anthracyclines are known to cause left ventricular (LV) dysfunction. While heart failure medications are frequently used, some patients may need consideration for device-based therapies such as cardiac resynchronisation therapy (CRT). However, the role of CRT in anthracycline-induced cardiomyopathy (AIC) is not well understood.
Methods
We performed a retrospective review of all patients undergoing CRT implantation at our centre from 2003 to 2019 with a diagnosis of AIC. The LV remodelling and survival outcomes of this population were obtained and then compared with consecutive patients with other aetiologies of non-ischaemic cardiomyopathy (NICM).
Results
A total of 34 patients underwent CRT implantation with a diagnosis of AIC with a mean age of 60.5±12.7 years, left ventricular ejection fraction (LVEF) of 21.7%±7.4%, and 11.3±7.5 years and 10.2±7.4 years from cancer diagnosis and last anthracycline exposure, respectively. At 9.6±8.1 months after CRT implantation, there was an increase of LVEF from 21.8%±7.6% to 30.4%±13.0% (p<0.001). Patients whose LVEF increased by at least 10% post-CRT implant (42.5% of cohort) survived significantly longer than patients who failed to improve their LVEF by that amount (p=0.01). A propensity matched analysis between patients with AIC and 369 consecutive patients with other aetiologies of NICM who underwent CRT implantation during the same period revealed no significant differences in improvement in LVEF or long-term survival.
Conclusions
Patients with AIC undergo LV remodelling with CRT at rates similar to other aetiologies of NICM. Furthermore, AIC post-CRT responders have a favourable long-term mortality compared with non-responders.

© Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.

Heart: 05 Sep 2021; epub ahead of print
Patel D, Kumar A, Moennich LA, Trulock K, ... Wilkoff BL, Rickard J
Heart: 05 Sep 2021; epub ahead of print | PMID: 34489312
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Impact:
Abstract

Association of heart failure and its comorbidities with loss of life expectancy.

Drozd M, Relton SD, Walker AMN, Slater TA, ... Kearney MT, Cubbon RM
Objective
Estimating survival can aid care planning, but the use of absolute survival projections can be challenging for patients and clinicians to contextualise. We aimed to define how heart failure and its major comorbidities contribute to loss of actuarially predicted life expectancy.
Methods
We conducted an observational cohort study of 1794 adults with stable chronic heart failure and reduced left ventricular ejection fraction, recruited from cardiology outpatient departments of four UK hospitals. Data from an 11-year maximum (5-year median) follow-up period (999 deaths) were used to define how heart failure and its major comorbidities impact on survival, relative to an age-sex matched control UK population, using a relative survival framework.
Results
After 10 years, mortality in the reference control population was 29%. In people with heart failure, this increased by an additional 37% (95% CI 34% to 40%), equating to an additional 2.2 years of lost life or a 2.4-fold (2.2-2.5) excess loss of life. This excess was greater in men than women (2.4 years (2.2-2.7) vs 1.6 years (1.2-2.0); p<0.001). In patients without major comorbidity, men still experienced excess loss of life, while women experienced less and were non-significantly different from the reference population (1 year (0.6-1.5) vs 0.4 years (-0.3 to 1); p<0.001). Accrual of comorbidity was associated with substantial increases in excess lost life, particularly for diabetes, chronic kidney and lung disease.
Conclusions
Comorbidity accounts for the majority of lost life expectancy in people with heart failure. Women, but not men, without comorbidity experience survival close to reference controls.

© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY. Published by BMJ.

Heart: 30 Aug 2021; 107:1417-1421
Drozd M, Relton SD, Walker AMN, Slater TA, ... Kearney MT, Cubbon RM
Heart: 30 Aug 2021; 107:1417-1421 | PMID: 33153996
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Impact:
Abstract

Revisiting heart failure assessment based on objective measures in NYHA functional classes I and II.

Blacher M, Zimerman A, Engster PHB, Grespan E, ... Biolo A, Rohde LE
Objective
New York Heart Association (NYHA) functional class plays a central role in heart failure (HF) assessment but might be unreliable in mild presentations. We compared objective measures of HF functional evaluation between patients classified as NYHA I and II in the Rede Brasileira de Estudos em Insuficiência Cardíaca (ReBIC)-1 Trial.
Methods
The ReBIC-1 Trial included outpatients with stable HF with reduced ejection fraction. All patients had simultaneous protocol-defined assessment of NYHA class, 6 min walk test (6MWT), N-terminal pro-brain natriuretic peptide (NT-proBNP) levels and patient\'s self-perception of dyspnoea using a Visual Analogue Scale (VAS, range 0-100).
Results
Of 188 included patients with HF, 122 (65%) were classified as NYHA I and 66 (35%) as NYHA II at baseline. Although NYHA class I patients had lower dyspnoea VAS Scores (median 16 (IQR, 4-30) for class I vs 27.5 (11-49) for class II, p=0.001), overlap between classes was substantial (density overlap=60%). A similar profile was observed for NT-proBNP levels (620 pg/mL (248-1333) vs 778 (421-1737), p=0.015; overlap=78%) and for 6MWT distance (400 m (330-466) vs 351 m (286-408), p=0.028; overlap=64%). Among NYHA class I patients, 19%-34% had one marker of HF severity (VAS Score >30 points, 6MWT <300 m or NT-proBNP levels >1000 pg/mL) and 6%-10% had two of them. Temporal change in functional class was not accompanied by variation on dyspnoea VAS (p=0.14).
Conclusions
Most patients classified as NYHA classes I and II had similar self-perception of their limitation, objective physical capabilities and levels of natriuretic peptides. These results suggest the NYHA classification poorly discriminates patients with mild HF.

© Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.

Heart: 30 Aug 2021; 107:1487-1492
Blacher M, Zimerman A, Engster PHB, Grespan E, ... Biolo A, Rohde LE
Heart: 30 Aug 2021; 107:1487-1492 | PMID: 33361353
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Impact:
Abstract

Cardiovascular or mortality risk of controlled hypertension and importance of physical activity.

Park S, Han K, Lee S, Kim Y, ... Kim YS, Kim DK
Objective
To investigate the risk of major adverse cardiac and cerebrovascular events (MACCEs) and all-cause death of patients with controlled hypertension and suggest the benefits of physical activity in their prognosis.
Methods
People aged 40-69 years from the prospective UK Biobank cohort (UKB, n=220 026) and the retrospective Korean National Health Insurance Service cohort (KNHIS, n=3 593 202) were included in this observational cohort study, excluding those with previous cerebrocardiovascular diseases or hypertension without treatment. The study groups were stratified into normotension, controlled hypertension (patients with hypertension with systolic blood pressure <140 mm Hg and diastolic blood pressure <90 mm Hg) and uncontrolled hypertension groups. The outcomes were MACCEs and all-cause mortality, analysed by Cox regression analysis.
Results
We included 161 405/18 844/39 777 and 3 122 890/383 828/86 484 individuals with normotension/controlled hypertension/uncontrolled hypertension state from the UKB and KNHIS cohorts, respectively. The controlled hypertension group showed significantly higher risk of MACCEs (UKB: adjusted HR 1.73 (95% CI 1.55 to 1.92); KNHIS: 1.46 (95% CI 1.43 to 1.49)) and all-cause mortality (UKB: adjusted HR 1.28 (95% CI 1.18 to 1.39); KNHIS: 1.29 (95% CI 1.26 to 1.32)) than individuals with normotension. The controlled hypertension group not involved in any moderate or moderate-to-vigorous physical activity showed high risk of adverse outcomes, which was comparable with or even higher than the risk of patients with uncontrolled hypertension who were engaged in physical activity.
Conclusions
Controlled hypertension is associated with residual risks of adverse outcomes. Clinicians may encourage physical activity for patients with controlled hypertension, not being reassured by their achieved target blood pressure values.

© Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.

Heart: 30 Aug 2021; 107:1472-1479
Park S, Han K, Lee S, Kim Y, ... Kim YS, Kim DK
Heart: 30 Aug 2021; 107:1472-1479 | PMID: 33402363
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Impact:
Abstract

MINOCA: a heterogenous group of conditions associated with myocardial damage.

Singh T, Chapman AR, Dweck MR, Mills NL, Newby DE
Myocardial infarction with non-obstructive coronary arteries (MINOCA) was first described over 80 years ago. The term has been widely and inconsistently used in clinical practice, influencing various aspects of disease classification, investigation and management. MINOCA encompasses a heterogenous group of conditions that include both atherosclerotic and non-atherosclerotic disease resulting in myocardial damage that is not due to obstructive coronary artery disease. In many ways, it is a term that describes a moment in the diagnostic pathway of the patient and is arguably not a diagnosis. Central to the definition is also the distinction between myocardial infarction and injury. The universal definition of myocardial infarction distinguishes acute myocardial infarction, including those with MINOCA, from other causes of myocardial injury by the presence of clinical evidence of ischaemia. However, these ischaemic features are often non-specific causing diagnostic confusion, and can create difficulties for patient management and follow-up. The purpose of this review is to summarise our current understanding of MINOCA and highlight important issues relating to the diagnosis, investigation and management of patients with MINOCA.

© Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.

Heart: 30 Aug 2021; 107:1458-1464
Singh T, Chapman AR, Dweck MR, Mills NL, Newby DE
Heart: 30 Aug 2021; 107:1458-1464 | PMID: 33568434
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Impact:
Abstract

Sex differences in investigations and outcomes among patients with type 2 myocardial infarction.

Kimenai DM, Lindahl B, Chapman AR, Baron T, ... Mills NL, Eggers KM
Objectives
Type 2 myocardial infarction (MI) is a heterogenous condition and whether there are differences between women and men is unknown. We evaluated sex differences in clinical characteristics, investigations and outcomes in patients with type 2 MI.
Methods
In the Swedish Web based system for Enhancement and Development of Evidence based care in Heart disease Evaluated According to Recommended Therapies (SWEDEHEART) registry, we compared patients admitted to coronary care units with a diagnosis of type 1 or type 2 MI. Sex-stratified Cox regression models evaluated the association with all-cause death in men and women separately.
Results
We included 57 264 (median age 73 years, 65% men) and 6485 (median age 78 years, 50% men) patients with type 1 and type 2 MI, respectively. No differences were observed in the proportion of men and women with type 2 MI who underwent echocardiography and coronary angiography, but women were less likely than men to have left ventricular (LV) impairment and obstructive coronary artery disease (CAD). Compared with type 1 MI, patients with type 2 MI had higher risk of death regardless of sex (men: adjusted HR 1.55 (95% CI 1.44 to 1.67); women: adjusted HR 1.34 (95% CI 1.24 to 1.45)). In those with type 2 MI, the risk of death was lower for women than men (adjusted HR 0.85 (95% CI 0.76 to 0.92) (men, reference)).
Conclusions
Type 2 MI occurred in men and women equally and we found no evidence of sex bias in the selection of patients for cardiac investigations. Patients with type 2 MI had worse outcomes, but women were less likely to have obstructive CAD or severe LV impairment and were more likely to survive than men.

© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

Heart: 30 Aug 2021; 107:1480-1486
Kimenai DM, Lindahl B, Chapman AR, Baron T, ... Mills NL, Eggers KM
Heart: 30 Aug 2021; 107:1480-1486 | PMID: 33879450
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Impact:
Abstract

Effect of medical treatment on heart failure incidence in patients with a systemic right ventricle.

Ladouceur M, Segura de la Cal T, Gaye B, Valentin E, ... Gatzoulis MA, Dimopoulos K
Background
To date, clinical trials have been underpowered to demonstrate a benefit from ACE inhibitors (ACEis) or angiotensin II receptor blockers (ARBs) in preventing systemic right ventricle (sRV) failure and disease progression in patients with transposition of the great arteries (TGA). This observational study aimed to estimate the effect of ACEi and ARB on heart failure (HF) incidence and mortality in a large population of patients with an sRV.
Methods
Data on all patients with an sRV under active follow-up at two tertiary centres between January 2007 and September 2018 were studied. The effect of ACEi and ARB on the incidence of HF and mortality was estimated using a propensity score weighting approach to control confounding.
Results
Among the 359 patients with an sRV (32.2 (IQR 26.4-38.3) years, 59.3% male, 66% complete TGA with atrial switch repair and 34% congenitally corrected TGA), 79 (22%) had a moderate to severe sRV dysfunction and 138 (38%) were treated with ACEi or ARB. Fourteen (3.6%) patients died, 8 (2.1%) underwent heart transplantation and 46 (11.8%) had a new HF event over a median follow-up of 7.1 (IQR 4.0-9.4) years. On multivariate Cox analysis with adjustment using propensity score weighting approaches, ACEi or ARBs treatment was not significantly associated with a lower HF incidence or mortality in patients with an sRV.
Conclusions
Despite significant neurohormonal activation described in patients with an sRV, there is still no evidence of a beneficial effect of ACEi or ARB on morbidity and mortality in this population.

© Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.

Heart: 30 Aug 2021; 107:1384-1389
Ladouceur M, Segura de la Cal T, Gaye B, Valentin E, ... Gatzoulis MA, Dimopoulos K
Heart: 30 Aug 2021; 107:1384-1389 | PMID: 33958396
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Impact:
Abstract

Cumulative burden of clinically significant aortic stenosis in community-dwelling older adults.

Owens DS, Bartz TM, Buzkova P, Massera D, ... Gottdiener JS, Kizer JR
Objectives
Current estimates of aortic stenosis (AS) frequency have mostly relied on cross-sectional echocardiographic or longitudinal administrative data, making understanding of AS burden incomplete. We performed case adjudications to evaluate the frequency of AS and assess differences by age, sex and race in an older cohort with long-term follow-up.
Methods
We developed case-capture methods using study echocardiograms, procedure and diagnosis codes, heart failure events and deaths for targeted review of medical records in the Cardiovascular Health Study to identify moderate or severe AS and related procedures or hospitalisations. The primary outcome was clinically significant AS (severe AS or procedure). Assessment of incident AS burden was based on subdistribution survival methods, while associations with age, sex and race relied on cause-specific survival methods.
Results
The cohort comprised 5795 participants (age 73±6, 42.2% male, 14.3% Black). Cumulative frequency of clinically significant AS at maximal 25-year follow-up was 3.69% (probable/definite) to 4.67% (possible/probable/definite), while the corresponding 20-year cumulative incidence was 2.88% to 3.71%. Of incident cases, about 85% had a hospitalisation for severe AS, but roughly half did not undergo valve intervention. The adjusted incidence of clinically significant AS was higher in men (HR 1.62 [95% CI 1.21 to 2.17]) and increased with age (HR 1.08 [95% CI 1.04 to 1.11]), but was lower in Blacks (HR 0.43 [95% CI 0.23 to 0.81]).
Conclusions
In this community-based study, we identified a higher burden of clinically significant AS than reported previously, with differences by age, sex and race. These findings have important implications for public health resource planning, although the lower burden in Blacks merits further study.

© Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.

Heart: 30 Aug 2021; 107:1493-1502
Owens DS, Bartz TM, Buzkova P, Massera D, ... Gottdiener JS, Kizer JR
Heart: 30 Aug 2021; 107:1493-1502 | PMID: 34083406
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Impact:
Abstract

Effectiveness of angiotensin-neprilysin inhibitor treatment versus renin-angiotensin system blockade in older adults with heart failure in clinical care.

Desai RJ, Patorno E, Vaduganathan M, Mahesri M, ... Solomon SD, Schneeweiss S
Objective
To evaluate the effectiveness of angiotensin receptor-neprilysin inhibitor (ARNI) versus renin-angiotensin system (RAS) blockade alone in older adults with heart failure with reduced ejection fraction (HFrEF).
Methods
We conducted a cohort study using US Medicare fee-for-service claims data (2014-2017). Patients with HFrEF ≥65 years were identified in two cohorts: (1) initiators of ARNI or RAS blockade alone (ACE inhibitor, ACEI; or angiotensin receptor blocker, ARB) and (2) switchers from an ACEI to either ARNI or ARB. HR with 95% CI from Cox proportional hazard regression and 1-year restricted mean survival time (RMST) difference with 95% CI were calculated for a composite outcome of time to first worsening heart failure event or all-cause mortality after adjustment for 71 pre-exposure characteristics through propensity score fine-stratification weighting. All analyses of initiator and switcher cohorts were conducted separately and then combined using fixed effects.
Results
51 208 patients with a mean age of 76 years were included, with 16 193 in the ARNI group. Adjusted HRs comparing ARNI with RAS blockade alone were 0.92 (95% CI 0.84 to 1.00) among initiators and 0.79 (95% CI 0.74 to 0.85) among switchers, with a combined estimate of 0.84 (95% CI 0.80 to 0.89). Adjusted 1-year RMST difference (95% CI) was 4 days in the initiator cohort (-1 to 9) and 12 days (8 to 17) in the switcher cohort, resulting in a pooled estimate of 9 days (6 to 12) favouring ARNI.
Conclusion
ARNI treatment was associated with lower risk of a composite effectiveness endpoint compared with RAS blockade alone in older adults with HFrEF.

© Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.

Heart: 30 Aug 2021; 107:1407-1416
Desai RJ, Patorno E, Vaduganathan M, Mahesri M, ... Solomon SD, Schneeweiss S
Heart: 30 Aug 2021; 107:1407-1416 | PMID: 34088766
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Impact:
Abstract

Clinical practice guideline for transcatheter versus surgical valve replacement in patients with severe aortic stenosis in Latin America.

Lamelas P, Ragusa MA, Bagur R, Jaffer I, ... Izcovich A, Endorsed by the Sociedad Latino Americana de Cardiología Intervencionista (SOLACI) and the Sociedad Interamericana de Cardiología (SIAC)
In elderly (75 years or older) patients living in Latin America with severe symptomatic aortic stenosis candidates for transfemoral approach, the panel suggests the use of transcatheter aortic valve implant (TAVI) over surgical aortic valve replacement (SAVR). This is a conditional recommendation, based on moderate certainty in the evidence (⨁⨁⨁Ο).This recommendation does not apply to patients in which there is a standard of care, like TAVI for patients at very high risk for cardiac surgery or inoperable patients, or SAVR for non-elderly patients (eg, under 65 years old) at low risk for cardiac surgery. The suggested age threshold of 75 years old is based on judgement of limited available literature and should be used as a guide rather than a determinant threshold.The conditional nature of this recommendation means that the majority of patients in this situation would want a transfemoral TAVI over SAVR, but some may prefer SAVR. For clinicians, this means that they must be familiar with the evidence supporting this recommendation and help each patient to arrive at a management decision integrating a multidisciplinary team discussion (Heart Team), patient\'s values and preferences through shared decision-making, and available resources. Policymakers will require substantial debate and the involvement of various stakeholders to implement this recommendation.

© Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.

Heart: 30 Aug 2021; 107:1450-1457
Lamelas P, Ragusa MA, Bagur R, Jaffer I, ... Izcovich A, Endorsed by the Sociedad Latino Americana de Cardiología Intervencionista (SOLACI) and the Sociedad Interamericana de Cardiología (SIAC)
Heart: 30 Aug 2021; 107:1450-1457 | PMID: 34127541
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Impact:
Abstract

Outcome and durability of mitral valve annuloplasty in atrial secondary mitral regurgitation.

Deferm S, Bertrand PB, Verhaert D, Dauw J, ... Vandervoort PM, Rega F
Objectives
Atrial secondary mitral regurgitation (ASMR) is a clinically distinct form of Carpentier type I mitral regurgitation (MR), rooted in excessive atrial and mitral annular dilation in the absence of left ventricular dysfunction. Mitral valve annuloplasty (MVA) is expected to provide a more durable solution for ASMR than for ventricular secondary MR (VSMR). Yet data on MR recurrence and outcome after MVA for ASMR are scarce. This study sought to investigate surgical outcomes and repair durability in patients with ASMR, as compared with a contemporary group of patients with VSMR.
Methods
Clinical and echocardiographic data from consecutive patients who underwent MVA to treat ASMR or VSMR in an academic centre were retrospectively analysed. Patient characteristics, operative outcomes, time to recurrence of ≥moderate MR and all-cause mortality were compared between patients with ASMR versus VSMR.
Results
Of the 216 patients analysed, 97 had ASMR opposed to 119 with VSMR and subvalvular leaflet tethering. Patients with ASMR were typically female (68.0% vs 33.6% in VSMR, p<0.001), with a history of atrial fibrillation (76.3% vs 33.6% in VSMR, p<0.001), paralleling a larger left atrial size (p<0.033). At a median follow-up of 3.3 (IQR 1.0-7.3) years, recurrence of ≥moderate MR was significantly lower in ASMR versus VSMR (7% vs 25% at 2 years, overall log-rank p=0.001), also when accounting for all-cause death as competing risk (subdistribution HR 0.50 in ASMR, 95% CI 0.29 to 0.88, p=0.016). Moreover, ASMR was associated with better overall survival compared with VSMR (adjusted HR 0.43 95% CI 0.22 to 0.82, p=0.011), independent from baseline European System for Cardiac Operative Risk Evaluation II surgical risk score.
Conclusion
Prognosis following MVA to treat ASMR is better, compared with VSMR as reflected by lower all-cause mortality and MR recurrence. Early distinction of secondary MR towards underlying ventricular versus atrial disease has important therapeutic implications.

© Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.

Heart: 30 Aug 2021; 107:1503-1509
Deferm S, Bertrand PB, Verhaert D, Dauw J, ... Vandervoort PM, Rega F
Heart: 30 Aug 2021; 107:1503-1509 | PMID: 34415852
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Impact:
Abstract

Incident aortic stenosis in 49 449 men and 42 229 women investigated with routine echocardiography.

Stewart S, Chan YK, Playford D, Strange GA, NEDA Investigators
Objective
We addressed the paucity of data describing the characteristics and consequences of incident aortic stenosis (AS).
Methods
Adults undergoing echocardiography with a native aortic valve (AV) and no AS were studied. Subsequent age-specific and sex-specific incidence of AS were derived from echocardiograms conducted a median of 2.8 years apart. Progressive AV dysfunction and individually linked mortality were examined per AS category.
Results
49 449 men (53.9%, 60.9±15.8 years) and 42 229 women (61.6±16.9 years) with no initial evidence of AS were identified. Subsequently, 6293 (6.9%) developed AS-comprising 5170 (5.6%), 636 (0.7%), 339 (0.4%) and 148 (0.2%) cases of mild, moderate, severe low-gradient and severe high-gradient AS, respectively. Age-adjusted incidence rates of all grades of AS were 17.5 cases per 1000 men/annum and 18.7 cases per 1000 women/annum: rising from ~5 to ~40 cases per 1000/annum in those aged <30 years vs >80 years. Median peak AV velocity increased by +0.57 (+0.36 to +0.80) m/s in mild AS compared with +2.75 (+2.40 to +3.19) m/s in severe high-gradient AS cases between first and last echocardiograms. During subsequent median 7.7 years follow-up, 24 577 of 91 678 cases (26.8%) died. Compared with no AS, the adjusted risk of all-cause mortality was 1.42-fold higher in mild AS, 1.92-fold higher in moderate AS, 1.95-fold higher in severe low-gradient AS and 2.27-fold higher in severe, high-gradient AS cases (all p<0.001).
Conclusions
New onset AS is a common finding among older patients followed up with echocardiography. Any grade of AS is associated with higher mortality, reinforcing the need for proactive vigilance.

© Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.

Heart: 24 Aug 2021; epub ahead of print
Stewart S, Chan YK, Playford D, Strange GA, NEDA Investigators
Heart: 24 Aug 2021; epub ahead of print | PMID: 34433635
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Impact:
Abstract

Sex disparity in subsequent outcomes in survivors of coronary heart disease.

Akyea RK, Kontopantelis E, Kai J, Weng SF, ... Asselbergs FW, Qureshi N
Objective
Evidence on sex differences in outcomes after developing coronary heart disease (CHD) has focused on recurrent CHD, all-cause mortality or revascularisation. We assessed sex disparities in subsequent major adverse cardiovascular events (MACE) in adults surviving their first-time CHD.
Methods
Using a population-based cohort obtained from the Clinical Practice Research Datalink (CPRD GOLD) linked to hospitalisation and death records in the UK, we identified 143 702 adults (aged ≥18 years) between 1 January 1998 and 31 December 2017 with no prior history of MACE. MACE outcome was a composite of recurrent CHD, stroke, peripheral vascular disease, heart failure and cardiovascular-related mortality. Multivariable models (Cox and competing risks regressions) were used to assess differences between sexes.
Results
There were 143 702 adults with any incident CHD (either angina, myocardial infarction or coronary revascularisation). Women (n=63 078, 43.9%) were older than men (median age, 73 vs 66 years). First subsequent MACE outcome was observed in 91 706 (63.8%). Women had a significantly lower risk of MACE (hazard ratio (HR), 0.68 (95% CI 0.67 to 0.69); sub-hazard ratio (HRsd), 0.71 (0.70 to 0.72), respectively) and recurrent CHD (n=66 543, 46.3%) (HR, 0.60 (0.59 to 0.61); HRsd, 0.62 (0.61 to 0.63)) when compared with men after incident CHD. However, women had a significantly higher risk of stroke (n=5740, 4.0%) (HR, 1.26 (1.19 to 1.33); HRsd, 1.32 (1.25 to 1.39)), heart failure (n=7905, 5.5%) (HR, 1.09 (1.04 to 1.15); HRsd, 1.13 (1.07 to 1.18)) and all-cause mortality (n=29 503, 20.5%) (HR, 1.05 (1.02 to 1.07); HRsd, 1.11 (1.08 to 1.13)).
Conclusions
After incident CHD, women have lower risk of composite MACE and recurrent CHD outcomes but higher risk of stroke, heart failure, and all-cause mortality compared with men.

© Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.

Heart: 23 Aug 2021; epub ahead of print
Akyea RK, Kontopantelis E, Kai J, Weng SF, ... Asselbergs FW, Qureshi N
Heart: 23 Aug 2021; epub ahead of print | PMID: 34429368
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Impact:
Abstract

Dilated cardiomyopathy: the role of genetics, highlighted in a family with Filamin C (FLNC) variant.

Dungu JN, Langley SG, Hardy-Wallace A, Li B, ... Homfray T, Savage HO
Dilated cardiomyopathy (DCM) is a heterogenous group of disorders characterised by left ventricular dilatation and dysfunction, in the absence of factors affecting loading conditions such as hypertension or valvular disease, or significant coronary artery disease. The prevalence of idiopathic DCM is estimated between 1:250 and 1:500 individuals. Determining the aetiology of DCM can be challenging, particularly when evaluating an individual and index case with no classical history or investigations pointing towards an obvious acquired cause, or no clinical clues in the family history to suggest a genetic cause. We present a family affected by DCM associated with Filamin C variant, causing sudden cardiac death at a young age and heart failure due to severe left ventricular impairment and myocardial scarring. We review the diagnosis and treatment of DCM, its genetic associations and potential acquired causes. Thorough assessment is mandatory to risk stratify and identify patients who may benefit from primary prevention implantable cardioverter defibrillator therapy according to international guidelines. Genetic testing has some limitations, and is positive in only 20%-35% of DCM, but should be considered in specific cases to identify families who may benefit from cascade screening after appropriate counselling. The management of often complex familial cardiomyopathy requires specialist input for every case, and the appropriate infrastructure to coordinate investigations.

© Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.

Heart: 19 Aug 2021; epub ahead of print
Dungu JN, Langley SG, Hardy-Wallace A, Li B, ... Homfray T, Savage HO
Heart: 19 Aug 2021; epub ahead of print | PMID: 34417207
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Impact:
Abstract

Clarifying the anatomy of the superior sinus venosus defect.

Relan J, Gupta SK, Rajagopal R, Ramakrishnan S, ... Rajashekar P, Anderson RH
Objectives
We sought to clarify the variations in the anatomy of the superior cavoatrial junction and anomalously connected pulmonary veins in patients with superior sinus venosus defects using computed tomographic (CT) angiography.
Methods
CT angiograms of 96 consecutive patients known to have superior sinus venosus defects were analysed.
Results
The median age of the patients was 34.5 years. In seven (7%) patients, the defect showed significant caudal extension, having a supero-inferior dimension greater than 25 mm. All patients had anomalous connection of the right superior pulmonary vein. The right middle and right inferior pulmonary vein were also connected anomalously in 88 (92%) and 17 (18%) patients, respectively. Anomalous connection of the right inferior pulmonary vein was more common in those with significant caudal extension of the defect (57% vs 15%, p=0.005). Among anomalously connected pulmonary veins, the right superior, middle, and inferior pulmonary veins were committed to the left atrium in 6, 17, and 11 patients, respectively. The superior caval vein over-rode the interatrial septum in 67 (70%) patients, with greater than 50% over-ride in 3 patients.
Conclusion
Anomalous connection of the right-sided pulmonary veins is universal, but is not limited to the right upper lobe. Not all individuals have over-riding of superior caval vein. In a minority of patients, the defect has significant caudal extension, and anomalously connected pulmonary veins are committed to the left atrium. These findings have significant clinical and therapeutic implications.

© Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.

Heart: 19 Aug 2021; epub ahead of print
Relan J, Gupta SK, Rajagopal R, Ramakrishnan S, ... Rajashekar P, Anderson RH
Heart: 19 Aug 2021; epub ahead of print | PMID: 34417206
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Impact:
Abstract

Remote ischaemic conditioning in ST elevation myocardial infarction: a registry-based randomised trial.

Bainey KR, Zheng Y, Coulden R, Sonnex E, ... Bastiany A, Welsh R
Objectives
Remote ischaemic conditioning (RIC) has been tested as a possible strategy for mitigating reperfusion injury in ST elevation myocardial infarction (STEMI) with primary percutaneous coronary intervention (PPCI). However, surrogate outcomes have shown inconsistent effects with lack of clinical correlation.
Methods
We performed a registry-based randomised study of patients with STEMI allocated to RIC (4 cycles of blood pressure cuff inflation to 200 mm Hg for 5 min of ischaemia followed by 5 min of reperfusion) or standard of care (SOC) during PPCI. We examined the associations of RIC on core laboratory measurements of myocardial perfusion, infarct size (IS), left ventricular (LV) performance and clinical outcomes.
Results
A total of 252 patients were enrolled. The median age was 61 (IQR: 55-70) years and 72.8% were male. Sum ST segment deviation resolution ≥50% was similar between RIC and SOC (65.2% vs 55.7%, p=0.269). In those with 3-day cardiovascular MRI (n=88), no difference in median (25th, 75th percentiles) IS (14.9% (4.5%, 23.1%) vs 16.1% (3.3%, 22.0%), p=0.980), LV dimensions (LV end-diastolic volume index: 78.7 (71.1, 91.2) mL/m2 vs 79.9 (71.2, 88.8) mL/m2, p=0.630; LV end-systolic volume index: 48.8 (35.7, 51.4) mL/m2 vs 37.9 (31.8, 47.5) mL/m2, p=0.551) or ejection fraction (50.0% (41.0%-55.0%) vs 50.0% (43.0%-56.0%), p=0.554) was demonstrated. Similar results were observed with 90-day cardiovascular MRI. At 1 year, the clinical composite of death, congestive heart failure, cardiogenic shock and recurrent myocardial infarction was similar in RIC and SOC (21.7% vs 13.3%, p=0.110).
Conclusions
In a contemporary registry-based randomised study of patients with STEMI undergoing PPCI, adjunctive therapy with RIC did not improve myocardial perfusion, reduce IS or alter LV performance. Consequently, there was no difference in clinical outcomes within 1 year.
Trial registration number
NCT03930589.

© Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.

Heart: 19 Aug 2021; epub ahead of print
Bainey KR, Zheng Y, Coulden R, Sonnex E, ... Bastiany A, Welsh R
Heart: 19 Aug 2021; epub ahead of print | PMID: 34417205
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Impact:
Abstract

Fluid challenge and balloon occlusion testing in patients with atrial septal defects.

D\'Alto M, Constantine A, Chessa M, Santoro G, ... Golino P, Dimopoulos K
Introduction
Careful, stepwise assessment is required in all patients with atrial septal defect (ASD) to exclude pulmonary vascular or left ventricular (LV) disease. Fluid challenge and balloon occlusion may unmask LV disease and post-capillary pulmonary hypertension, but their role in the evaluation of patients with \'operable\' ASDs is not well established.
Methods
We conducted a prospective study in three Italian specialist centres between 2018 and 2020. Patients selected for percutaneous ASD closure underwent assessment at baseline and after fluid challenge, balloon occlusion and both.
Results
Fifty patients (46 (38.2, 57.8) years, 72% female) were included. All had a shunt fraction >1.5, pulmonary vascular resistance (PVR) <5 Wood Units (WU) and pulmonary arterial wedge pressure (PAWP) <15 mm Hg. Individuals with a PVR ≥2 WU at baseline (higher PVR group) were older, more symptomatic, with a higher baseline systemic vascular resistance (SVR) than the lower PVR group (all p<0.0001). Individuals with a higher PVR experienced smaller increases in pulmonary blood flow following fluid challenge (0.3 (0.1, 0.5) vs 2.0 (1.5, 2.8) L/min, p<0.0001). Balloon occlusion led to a more marked fall in SVR (p<0.0001) and a larger increase in systemic blood flow (p=0.024) in the higher PVR group. No difference was observed in PAWP following fluid challenge and/or balloon occlusion between groups; four (8%) patients reached a PAWP ≥18 mm Hg following the addition of fluid challenge to balloon occlusion testing.
Conclusions
In adults with ASD without overt LV disease, even small rises in PVR may have significant implications on cardiovascular haemodynamics. Fluid challenge may provide additional information to balloon occlusion in this setting.

© Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.

Heart: 18 Aug 2021; epub ahead of print
D'Alto M, Constantine A, Chessa M, Santoro G, ... Golino P, Dimopoulos K
Heart: 18 Aug 2021; epub ahead of print | PMID: 34413090
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Impact:
Abstract

Association between cardiologist evaluation and mortality in myocardial injury after non-cardiac surgery.

Park J, Oh AR, Kwon JH, Kim S, ... Sung J, Lee SH
Objective
Myocardial injury after non-cardiac surgery (MINS) is strongly associated with mortality, but few studies assessed treatment strategies. This study aimed to identify whether evaluation by cardiologists could reduce mortality in MINS patients.
Methods
From a single-centre retrospective cohort, we enrolled a total of 5633 adult patients diagnosed with MINS between January 2010 and June 2019. The patients were divided into two groups based on evaluation by cardiologist, which was defined as a cardiology consultation or transfer to the cardiology department. For the outcome, 30-day mortality was compared in crude and propensity-score matched populations.
Results
Of a total of 5633 patients, 2120 (37.6%) were evaluated by cardiologists and 3513 (62.4%) were not. Mortality during the first 30 days after surgery was significantly lower in MINS patients who were evaluated by cardiologists compared with those who were not (5.8% vs 8.3%; HR, 0.64; 95% CI 0.51 to 0.80; p<0.001 for all-cause mortality and 1.6% vs 2.0; HR 0.62; 95% CI 0.40 to 0.96; p=0.03 for cardiovascular mortality). The propensity score matched analysis showed similar results (5.6% vs 8.6%; HR 0.64; 95% CI 0.50 to 0.81; p<0.001 for all-cause mortality and 1.3% vs 2.2%; HR 0.58; 95% CI 0.35 to 0.95; p=0.03 for cardiovascular mortality).
Conclusions
Cardiologist evaluation was associated with lower mortality in patients diagnosed with MINS. Further studies are needed to identify effective treatment strategies for MINS.
Trial registration number
KCT0004244.

© Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.

Heart: 15 Aug 2021; epub ahead of print
Park J, Oh AR, Kwon JH, Kim S, ... Sung J, Lee SH
Heart: 15 Aug 2021; epub ahead of print | PMID: 34400475
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Impact:
Abstract

Analysis of outcome of 6-month readmissions after percutaneous left atrial appendage occlusion.

Morita S, Malik AH, Kuno T, Ando T, ... Yandrapalli S, Briasoulis A
Objective
Percutaneous left atrial appendage occlusion (LAAO) is an alternative strategy for prevention of thromboembolic events in patients with atrial fibrillation and unsuitable for long-term oral anticoagulation. The study aimed to evaluate the causes and timing of readmissions within 6 months following percutaneous LAAO in a real-world setting.
Methods
We conducted a retrospective cohort study of percutaneous LAAO performed in the USA between January and June of 2016-2018 using the Nationwide Readmissions Database.
Results
Overall, 12 446 patients who underwent LAAO were included in the analyses and 3477 patients (28%) were readmitted within 6 months following the interventions. Readmitted patients were more often women (p=0.001). The index hospitalisation was characterised by longer duration of hospital stay (p<0.001) and complicated with acute kidney injury (p<0.001) among readmitted patients compared with those without readmissions. Readmissions within 6 months following the index intervention were mainly due to heart failure (13%) and gastrointestinal bleeding (12%). Characteristics associated with readmissions due to heart failure included previously known heart failure (HR 2.39; 95% CI 1.70 to 3.37), valvular heart disease (HR 1.39; 95% CI 1.05 to 1.84) and chronic kidney disease (HR 1.42; 95% CI 1.03 to 1.94). Readmissions due to gastrointestinal bleeding were associated with diabetes mellitus (HR 1.78; 95% CI 1.25 to 2.53), chronic kidney disease (HR 1.86; 95% CI 1.23 to 2.81) and previous anaemia (HR 2.41; 95% CI 1.54 to 3.77).
Conclusions
After percutaneous LAAO, over a quarter of the patients in the USA required rehospitalisation within 6 months, mainly due to heart failure and gastrointestinal bleeding.

© Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.

Heart: 15 Aug 2021; epub ahead of print
Morita S, Malik AH, Kuno T, Ando T, ... Yandrapalli S, Briasoulis A
Heart: 15 Aug 2021; epub ahead of print | PMID: 34400473
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Impact:
Abstract

Gastrointestinal bleeding risk following concomitant treatment with oral glucocorticoids in patients on non-vitamin K oral anticoagulants.

Holt A, Blanche P, Zareini B, Rasmussen PV, ... McGettigan P, Lamberts M
Objective
Gastrointestinal bleeding (GIB) risk in relation to concomitant treatment with non-vitamin K oral anticoagulants (NOAC) and oral glucocorticoids is insufficiently explored. We aimed to investigate the short-term risk following coexposure.
Methods
This is a register-based, nationwide Danish study including patients with atrial fibrillation on NOACs during 2012-2018. Patients were defined as exposed to oral glucocorticoids if they claimed a prescription within 60 days prior to GIB. We investigated the associations between GIB and oral glucocorticoid exposure, reporting HRs via a nested case-control design and absolute risk via a cohort design. Matching terms were age, sex, calendar year, follow-up time and NOAC agent.
Results
98 376 patients on NOACs (median age: 75 years (IQR: 68-82), 44% female) were included, and 16% redeemed at least one oral glucocorticoid prescription within 3 years. HRs of GIB were increased comparing exposed with non-exposed patients (<20 mg daily dose, HR 1.54 (95% CI 1.29 to 1.84); ≥20 mg daily dose, HR 2.19 (95% CI 1.81 to 2.65)). 60-day standardised absolute risk of GIB following first claimed oral glucocorticoid prescription increased compared with non-exposed: 60-day absolute risk: 0.71% (95% CI 0.58% to 0.85%) vs 0.38% (95% CI 0.32% to 0.43%). The relative risk was elevated as well: risk ratio of 1.89 (95% CI 1.43 to 2.36).
Conclusions
Concomitant treatment with NOACs and oral glucocorticoids was associated with a short-term rate and risk increase of GIB compared with patients only on NOACs. This could have implications for clinical management, necessitating closer monitoring or other risk mitigation strategies during episodes of cotreatment with oral glucocorticoids.

© Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.

Heart: 12 Aug 2021; epub ahead of print
Holt A, Blanche P, Zareini B, Rasmussen PV, ... McGettigan P, Lamberts M
Heart: 12 Aug 2021; epub ahead of print | PMID: 34389550
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Impact:
Abstract

Stroke in patients with secundum atrial septal defect and sequelae after transcatheter closure.

Dolgner SJ, Steinberg ZL, Jones TK, Reisman M, Buber J
Objective
To evaluate the frequency of and risk factors for stroke as a presenting feature in adult patients with secundum atrial septal defect (ASD); rates of post-closure atrial fibrillation (AF) and stroke were also assessed.
Methods
We retrospectively reviewed adult patients who presented with an ASD between 2002 and 2018, excluding those with known atrial arrhythmias. Risk factors for stroke were identified using multivariable logistic regression. Post-closure stroke was evaluated using survival analysis stratified by the presence of post-procedure AF.
Results
Of 346 patients with ASD (median age 44 years), 34 (10%) presented with a history of stroke. Independent risk factors included elevated body mass index over 25 (OR: 18.2; 95% CI: 4.0 to 82.2; p<0.001), smoking (OR: 9.5; 95% CI: 3.8 to 23.9; p<0.001) and a prominent Eustachian valve (OR: 9.2; 95% CI: 3.4 to 25.2; p<0.001). A scoring system based on these three parameters provided robust stroke risk stratification. During a median follow-up of 12 months after closure, 12 patients (4%) experienced AF and 4 patients (1%) had a new stroke. AF was highly associated with development of stroke post-closure (p<0.001).
Conclusions
In this study population, the incidence of stroke prior to ASD closure among patients without atrial arrhythmias was 10%. Risk factors included obesity, smoking and prominent Eustachian valve anatomy. Lifestyle changes should be recommended for at-risk patients, and it may be reasonable to consider ASD closure in the absence of haemodynamic indications in patients at increased risk of stroke.

© Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.

Heart: 10 Aug 2021; epub ahead of print
Dolgner SJ, Steinberg ZL, Jones TK, Reisman M, Buber J
Heart: 10 Aug 2021; epub ahead of print | PMID: 34380660
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Impact:
Abstract

Moderate excess alcohol consumption and adverse cardiac remodelling in dilated cardiomyopathy.

Tayal U, Gregson J, Buchan R, Whiffin N, ... Cook SA, Prasad SK
Objective
The effect of moderate excess alcohol consumption is widely debated and has not been well defined in dilated cardiomyopathy (DCM). There is need for a greater evidence base to help advise patients. We sought to evaluate the effect of moderate excess alcohol consumption on cardiovascular structure, function and outcomes in DCM.
Methods
Prospective longitudinal observational cohort study. Patients with DCM (n=604) were evaluated for a history of moderate excess alcohol consumption (UK government guidelines; >14 units/week for women, >21 units/week for men) at cohort enrolment, had cardiovascular magnetic resonance and were followed up for the composite endpoint of cardiovascular death, heart failure and arrhythmic events. Patients meeting criteria for alcoholic cardiomyopathy were not recruited.
Results
DCM patients with a history of moderate excess alcohol consumption (n=98, 16%) had lower biventricular function and increased chamber dilatation of the left ventricle, right ventricle and left atrium, as well as increased left ventricular hypertrophy compared with patients without moderate alcohol consumption. They were more likely to be male (alcohol excess group: n=92, 94% vs n=306, 61%, p=<0.001). After adjustment for biological sex, moderate excess alcohol was not associated with adverse cardiac structure. There was no difference in midwall myocardial fibrosis between groups. Prior moderate excess alcohol consumption did not affect prognosis (HR 1.29, 95% CI 0.73 to 2.26, p=0.38) during median follow-up of 3.9 years.
Conclusion
DCM patients with moderate excess alcohol consumption have adverse cardiac structure and function at presentation, but this is largely due to biological sex. Alcohol may contribute to sex-specific phenotypic differences in DCM. These findings help to inform lifestyle discussions for patients with DCM.

© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY. Published by BMJ.

Heart: 10 Aug 2021; epub ahead of print
Tayal U, Gregson J, Buchan R, Whiffin N, ... Cook SA, Prasad SK
Heart: 10 Aug 2021; epub ahead of print | PMID: 34380661
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Impact:
Abstract

Refined atrial fibrillation screening and cost-effectiveness in the German population.

Schnabel RB, Wallenhorst C, Engler D, Blankenberg S, ... Freedman B, Gutenberg Health Study investigators
Objective
Little is known on optimal screening population for detecting new atrial fibrillation (AF) in the community. We describe characteristics and estimate cost-effectiveness for a single timepoint electrocardiographic screening.
Methods
We performed a 12-lead ECG in the German population-based Gutenberg Health Study between 2007 and 2012 (n=15 010), mean age 55±11 years, 51% men and collected more than 120 clinical and biomarker variables, including N-terminal pro B-type natriuretic peptide (Nt-proBNP), risk factors, disease symptoms and echocardiographic variables.
Results
Of 15 010 individuals, 466 (3.1%) had AF. New AF was found in 32 individuals, 0.2% of the total sample, 0.5% of individuals aged 65-74 years and predominantly men (86%). The classical risk factor burden was high in individuals with new AF. The median estimated stroke risk was 2.2%/year, while risk of developing heart failure was 21% over 10 years. In the 65-74 year age group, the cost per quality-adjusted life-year gained resulting from a single timepoint screening was €30 361. In simulations, the costs were highly sensitive to AF detection rates, proportion of treatment and type of oral anticoagulant. Prescreening by Nt-proBNP measurements was not cost-effective in the current setting.
Conclusions
In our middle-aged population cohort, we identified 0.2% new AF by single timepoint screening. There was a significant estimated risk of stroke and heart failure in these individuals. Cost-effectiveness for screening may be reached in individuals aged 65 years and older. The simple age cut-off is not improved by using Nt-proBNP as a biomarker to guide a screening programme.

© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

Heart: 09 Aug 2021; epub ahead of print
Schnabel RB, Wallenhorst C, Engler D, Blankenberg S, ... Freedman B, Gutenberg Health Study investigators
Heart: 09 Aug 2021; epub ahead of print | PMID: 34376487
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Abstract

Diagnostic accuracy of handheld cardiac ultrasound device for assessment of left ventricular structure and function: systematic review and meta-analysis.

Jenkins S, Alabed S, Swift A, Marques G, ... Vassiliou VS, Garg P
Objective
Handheld ultrasound devices (HUD) has diagnostic value in the assessment of patients with suspected left ventricular (LV) dysfunction. This meta-analysis evaluates the diagnostic ability of HUD compared with transthoracic echocardiography (TTE) and assesses the importance of operator experience.
Methods
MEDLINE and EMBASE databases were searched in October 2020. Diagnostic studies using HUD and TTE imaging to determine LV dysfunction were included. Pooled sensitivities and specificities, and summary receiver operating characteristic curves were used to determine the diagnostic ability of HUD and evaluate the impact of operator experience on test accuracy.
Results
Thirty-three studies with 6062 participants were included in the meta-analysis. Experienced operators could predict reduced LV ejection fraction (LVEF), wall motion abnormality (WMA), LV dilatation and LV hypertrophy with pooled sensitivities of 88%, 85%, 89% and 85%, respectively, and pooled specificities of 96%, 95%, 98% and 91%, respectively. Non-experienced operators are able to detect cardiac abnormalities with reasonable sensitivity and specificity. There was a significant difference in the diagnostic accuracy between experienced and inexperienced users in LV dilatation, LVEF (moderate/severe) and WMA. The diagnostic OR for LVEF (moderate/severe), LV dilatation and WMA in an experienced hand was 276 (95% CI 58 to 1320), 225 (95% CI 87 to 578) and 90 (95% CI 31 to 265), respectively, compared with 41 (95% CI 18 to 94), 45 (95% CI 16 to 123) and 28 (95% CI 20 to 41), respectively, for inexperienced users.
Conclusion
This meta-analysis is the first to establish HUD as a powerful modality for predicting LV size and function. Experienced operators are able to accurately diagnose cardiac disease using HUD. A cautious, supervised approach should be implemented when imaging is performed by inexperienced users. This study provides a strong rationale for considering HUD as an auxiliary tool to physical examination in secondary care, to aid clinical decision making when considering referral for TTE.
Trial registration number
CRD42020182429.

© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY. Published by BMJ.

Heart: 05 Aug 2021; epub ahead of print
Jenkins S, Alabed S, Swift A, Marques G, ... Vassiliou VS, Garg P
Heart: 05 Aug 2021; epub ahead of print | PMID: 34362772
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Abstract

Role of digital health in detection and management of atrial fibrillation.

Tooley JE, Perez MV
Atrial fibrillation is a common arrhythmia associated with significant morbidity, mortality and decreased quality of life. Mobile health devices marketed directly to consumers capable of detecting atrial fibrillation through methods including photoplethysmography, single-lead ECG as well as contactless methods are becoming ubiquitous. Large-scale screening for atrial fibrillation is feasible and has been shown to detect more cases than usual care-however, controversy still exists surrounding screening even in older higher risk populations. Given widespread use of mobile health devices, consumer-driven screening is happening on a large scale in both low-risk and high-risk populations. Given that young people make up a large portion of early adopters of mobile health devices, there is the potential that many more patients with early onset atrial fibrillation will come to clinical attention requiring possible referral to genetic arrythmia clinic. Physicians need to be familiar with these technologies, and understand their risks, and limitations. In the current review, we discuss current mobile health devices used to detect atrial fibrillation, recent and upcoming trials using them for diagnosis of atrial fibrillation, practical recommendations for patients with atrial fibrillation diagnosed by a mobile health device and special consideration in young patients.

© Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.

Heart: 02 Aug 2021; epub ahead of print
Tooley JE, Perez MV
Heart: 02 Aug 2021; epub ahead of print | PMID: 34344729
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Abstract

Diagnosis and management of cardiac allograft vasculopathy.

Ortega-Legaspi JM, Bravo PE
One of the main causes of death beyond the first year after heart transplantation is cardiac allograft vasculopathy (CAV). This review summarises the current understanding of its complex pathophysiology, detection and treatment, including the available data on non-invasive imaging modalities used for screening and diagnosis. A better understanding of this entity is crucial to improving the long-term outcomes of the growing population of patients with a heart transplant.

© Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.

Heart: 01 Aug 2021; epub ahead of print
Ortega-Legaspi JM, Bravo PE
Heart: 01 Aug 2021; epub ahead of print | PMID: 34340994
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Abstract

Non-vitamin K antagonist oral anticoagulants, proton pump inhibitors and gastrointestinal bleeds.

Komen J, Pottegård A, Hjemdahl P, Mantel-Teeuwisse AK, ... Forslund T, Klungel O
Objective
To evaluate if proton pump inhibitor (PPI) treatment reduces the risk of upper gastrointestinal bleeding (UGIB) in patients with atrial fibrillation (AF) treated with non-vitamin K antagonist oral anticoagulants (NOACs).
Design
We used a common protocol, common data model approach to conduct a cohort study including patients with AF initiated on a NOAC in Stockholm, Denmark and the Netherlands from April 2011 until July 2018. The outcome of interest was a UGIB diagnosed in a secondary care inpatient setting. We used an inverse probability weighted (IPW) Poisson regression to calculate incidence rate ratios (IRRs), contrasting PPI use to no PPI use periods.
Results
In 164 290 NOAC users with AF, providing 272 570 years of follow-up and 39 938 years of PPI exposure, 806 patients suffered a UGIB. After IPW, PPI use was associated with lower UGIB rates (IRR: 0.75; 95% CI: 0.59 to 0.95). On an absolute scale, the protective effect was modest, and was found to be largest in high-risk patients, classified as age 75-84 years (number needed to treat for 1 year (NNTY): 787), age ≥85 years (NNTY: 667), HAS-BLED score ≥3 (NNTY: 378) or on concomitant antiplatelet therapy (NNTY: 373).
Conclusion
Concomitant treatment with a PPI in NOAC-treated patients with AF is associated with a reduced risk of severe UGIB. This indicates that PPI cotreatment can be considered, in particular among the elderly patients, patients with a HAS-BLED score ≥3, and/or in patients on concomitant antiplatelet therapy.

© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

Heart: 01 Aug 2021; epub ahead of print
Komen J, Pottegård A, Hjemdahl P, Mantel-Teeuwisse AK, ... Forslund T, Klungel O
Heart: 01 Aug 2021; epub ahead of print | PMID: 34340993
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Abstract

Efficacy and safety of diuretics in heart failure with preserved ejection fraction: a scoping review.

Singh A, Agarwal A, Wafford QE, Shah SJ, Huffman M, Khan S
Objective
Diuretics reduce congestion in patients with heart failure with preserved ejection fraction (HFpEF). However, comparison of clinical effects across diuretic classes or combinations of diuretics in patients with HFpEF are not well described. Therefore, we sought to conduct a scoping review to map trial data of diuretic efficacy and safety in patients with HFpEF.
Review methods and results
We searched multiple bibliometric databases for published literature and ClinicalTrials.gov, and hand searched unpublished studies comparing different classes of diuretics to usual care or placebo in patients with HFpEF. We included randomised controlled trials or quasi-experimental studies. Two authors independently screened and extracted key data using a structured form. We identified 13 published studies on diuretics in HFpEF, with 1 evaluating thiazide use, 7 on mineralocorticoid receptor antagonists (MRAs) and 5 on sodium-glucose co-transporter 2 inhibitors (SGLT2i). There remain 17 ongoing trials evaluating loop diuretics (n=1), MRAs (n=5), SGLT2i (n=10) and a polydiuretic (n=1), including 2 well-powered trials of SGLT2i that will be completed in 2021.
Conclusions
The limited number of published trials evaluating different classes of diuretics in patients with HFpEF have been generally small and short term. Ongoing and emerging trials of single or combination diuretics with greater power will be useful to better define their safety and efficacy. SCOPING REVIEW REGISTRATION: doi:10.18131/g3-dejv-tm77.

© Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.

Heart: 01 Aug 2021; epub ahead of print
Singh A, Agarwal A, Wafford QE, Shah SJ, Huffman M, Khan S
Heart: 01 Aug 2021; epub ahead of print | PMID: 34340995
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Older ...

This program is still in alpha version.