Journal: Heart

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Abstract

Role of beta blockers following percutaneous coronary intervention for acute coronary syndrome.

Peck KY, Andrianopoulos N, Dinh D, Roberts L, ... Freeman M, Teh AW
Aims
There is a paucity of evidence supporting routine beta blocker (BB) use in patients undergoing percutaneous coronary intervention (PCI) for acute coronary syndrome (ACS). The aim of this study was to evaluate BB use post PCI and its association with mortality. Furthermore, the study aimed to evaluate the association between BB and mortality in the subgroups of patients with left ventricular ejection fraction (LVEF) <35%, LVEF 35%-50% and LVEF >50%.
Methods
Using a large PCI registry, data from patients with ACS between January 2005 and June 2017 who were alive at 30 days were analysed. Those patients taking BB at 30 days were compared with those who were not taking BB. The primary outcome was all-cause mortality. The mean follow-up was 5.3±3.5 years.
Results
Of the 17 562 patients, 83.3% were on BB. Mortality was lower in the BB group (13.1% vs 19.5%, p=0.0001). Multivariable Cox proportional hazards model showed that BB use was associated with lower overall mortality (adjusted HR 0.87, 95% CI 0.78 to 0.97, p=0.014). In the subgroup analysis, BB use was associated with reduced mortality in LVEF <35% (adjusted HR 0.63, 95% CI 0.44 to 0.91, p=0.013), LVEF 35%-50% (adjusted HR 0.80, 95% CI 0.68 to 0.95, p=0.01), but not LVEF >50% (adjusted HR 1.03, 95% CI 0.87 to 1.21, p=0.74).
Conclusion
BB use remains high and is associated with reduced mortality. This reduction in mortality is primarily seen in those with reduced ejection fraction, but not in those with preserved ejection fraction.

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

Heart: 29 Apr 2021; 107:728-733
Peck KY, Andrianopoulos N, Dinh D, Roberts L, ... Freeman M, Teh AW
Heart: 29 Apr 2021; 107:728-733 | PMID: 32887736
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Abstract

Premature permanent discontinuation of apixaban or warfarin in patients with atrial fibrillation.

Carnicelli AP, Al-Khatib SM, Xavier D, Dalgaard F, ... Wallentin L, Granger CB
Aims
The ARISTOTLE (Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation) trial randomised patients with atrial fibrillation at risk of stroke to apixaban or warfarin. We sought to describe patients from ARISTOTLE who prematurely permanently discontinued study drug.
Methods/results
We performed a posthoc analysis of patients from ARISTOTLE who prematurely permanently discontinued study drug during the study or follow-up period. Discontinuation rates and reasons for discontinuation were described. Death, thromboembolism (stroke, transient ischaemic attack, systemic embolism), myocardial infarction and major bleeding rates were stratified by ≤30 days or >30 days after discontinuation. A total of 4063/18 140 (22.4%) patients discontinued study drug at a median of 7.3 (2.2, 15.2) months after randomisation. Patients with discontinuation were more likely to be female and had a higher prevalence of cardiovascular disease, diabetes, renal impairment and anaemia. Premature permanent discontinuation was more common in those randomised to warfarin than apixaban (23.4% vs 21.4%; p=0.002). The most common reasons for discontinuation were patient request (46.1%) and adverse event (34.9%), with no significant difference between treatment groups. The cumulative incidence of clinical events ≤30 days after premature permanent discontinuation for all-cause death, thromboembolism, myocardial infarction, and major bleeding was 5.8%, 2.6%, 0.9%, and 3.0%, respectively. No significant difference was seen between treatment groups with respect to clinical outcomes after discontinuation.
Conclusion
Premature permanent discontinuation of study drug in ARISTOTLE was common, less frequent in patients receiving apixaban than warfarin and was followed by high 30-day rates of death, thromboembolism and major bleeding. Initiatives are needed to reduce discontinuation of oral anticoagulation.

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

Heart: 29 Apr 2021; 107:713-720
Carnicelli AP, Al-Khatib SM, Xavier D, Dalgaard F, ... Wallentin L, Granger CB
Heart: 29 Apr 2021; 107:713-720 | PMID: 32938772
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Abstract

Clinical and echocardiographic outcomes in heart failure associated with methamphetamine use and cessation.

Bhatia HS, Nishimura M, Dickson S, Adler E, Greenberg B, Thomas IC
Objective
Methamphetamine use is associated with systolic dysfunction, pulmonary arterial hypertension and may also be associated with diastolic dysfunction. The impact of methamphetamine cessation on methamphetamine-associated heart failure (MethHF) remains poorly characterised. We aimed to longitudinally characterise methamphetamine-associated heart failure patients with reduced (METHrEF) and preserved (METHpEF) left ventricular ejection fraction (EF), and evaluate the relationship between methamphetamine cessation and clinical outcomes.
Methods
We performed a retrospective cohort study, and reviewed medical records of patients with METHrEF, METHpEF and heart failure controls without methamphetamine use. Echocardiographic variables were recorded for up to 12 months, with clinical follow-up extending to 24 months.
Results
Among METHrEF patients (n=28, mean age 51±9 years, 82.1% male), cessation was associated with improvement in EF (+10.6±13.1%, p=0.009) and fewer heart failure admissions per year compared with continued use (median 0.0, IQR 0.0-1.0 vs median 2.0, IQR 1.0-3.0, p=0.039). METHpEF patients (n=28, mean age 50±8 years, 60.7% male) had higher baseline right ventricular systolic pressure (median 53.44, IQR 43.70-84.00 vs median 36.64, IQR 29.44-45.95, p=0.011), and lower lateral E/E\' ratio (8.1±3.6 vs 11.2±4., p<0.01) compared with controls (n=32). Significant improvements in echocardiographic parameters and clinical outcomes were not observed following cessation in this group.
Conclusions
METHrEF patients who cease methamphetamine use have significant improvement in left ventricular systolic function and fewer heart failure admissions, suggesting that METHrEF may be reversible. Echocardiographic parameters suggest that some patients with METHpEF may have pulmonary hypertension in the absence of overt signs of left ventricular diastolic dysfunction, but additional study is needed to characterise this patient cohort.

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

Heart: 29 Apr 2021; 107:741-747
Bhatia HS, Nishimura M, Dickson S, Adler E, Greenberg B, Thomas IC
Heart: 29 Apr 2021; 107:741-747 | PMID: 33020227
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Abstract

Prognostic significance of natriuretic peptide levels in atrial fibrillation without heart failure.

Hamatani Y, Iguchi M, Ueno K, Aono Y, ... Morita S, Akao M
Objectives
Natriuretic peptides are an important prognostic marker in patients with heart failure (HF). However, little is known regarding their prognostic significance in patients with atrial fibrillation (AF) without HF and natriuretic peptides levels are underused in these patients in daily practice.
Methods
The Fushimi AF Registry is a community-based prospective survey of patients with AF in Fushimi-ku, Kyoto, Japan. We investigated patients with AF without HF (defined as prior HF hospitalisation, New York Heart Association functional class≥2 or left ventricular ejection fraction<40%) using the data of B-type natriuretic peptide (BNP, n=388) or N-terminal pro-B-type natriuretic peptide (NT-proBNP, n=771) at enrolment. BNPs were converted to NT-proBNP using a conversion formula. We divided the patients according to quartiles of NT-proBNP levels and compared the backgrounds and outcomes.
Results
Of 1159 patients (mean age: 72.1±10.2 years, median CHA2DS2-VASc score: 3 and oral anticoagulant (OAC) prescription: 671 (56%)), the median NT-proBNP level was 488 (IQR 169-1015) ng/L. Patients with high NT-proBNP levels were older, had higher CHA2DS2-VASc scores and had more OAC prescription (all p<0.001). Kaplan-Meier curves demonstrated that NT-proBNP levels were significantly associated with higher incidences of stroke/systemic embolism, all-cause death and HF hospitalisation during a median follow-up period of 5.0 years (log rank, all p<0.001). Multivariable Cox regression analyses revealed that NT-proBNP levels were an independent predictor of adverse outcomes even after adjustment by various confounders.
Conclusion
NT-proBNP levels are a significant prognostic marker for adverse outcomes in patients with AF without HF and may have clinical value.
Trial registration number
UMIN000005834.

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Heart: 29 Apr 2021; 107:705-712
Hamatani Y, Iguchi M, Ueno K, Aono Y, ... Morita S, Akao M
Heart: 29 Apr 2021; 107:705-712 | PMID: 33219109
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Abstract

Cardiovascular magnetic resonance imaging: emerging techniques and applications.

Chowdhary A, Garg P, Das A, Nazir MS, Plein S
This review gives examples of emerging cardiovascular magnetic resonance (CMR) techniques and applications that have the potential to transition from research to clinical application in the near future. Four-dimensional flow CMR (4D-flow CMR) allows time-resolved three-directional, three-dimensional (3D) velocity-encoded phase-contrast imaging for 3D visualisation and quantification of valvular or intracavity flow. Acquisition times of under 10 min are achievable for a whole heart multidirectional data set and commercial software packages are now available for data analysis, making 4D-flow CMR feasible for inclusion in clinical imaging protocols. Diffusion tensor imaging (DTI) is based on the measurement of molecular water diffusion and uses contrasting behaviour in the presence and absence of boundaries to infer tissue structure. Cardiac DTI is capable of non-invasively phenotyping the 3D micro-architecture within a few minutes, facilitating transition of the method to clinical protocols. Hybrid positron emission tomography-magnetic resonance (PET-MR) provides quantitative PET measures of biological and pathological processes of the heart combined with anatomical, morphological and functional CMR imaging. Cardiac PET-MR offers opportunities in ischaemic, inflammatory and infiltrative heart disease.

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

Heart: 29 Apr 2021; 107:697-704
Chowdhary A, Garg P, Das A, Nazir MS, Plein S
Heart: 29 Apr 2021; 107:697-704 | PMID: 33402364
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Abstract

Incidence and predictors of stroke in patients with rheumatic heart disease.

Vasconcelos M, Vasconcelos L, Ribeiro V, Campos C, ... Teixeira AL, Nunes MCP
Objective
Ischaemic stroke is a severe complication of rheumatic heart disease (RHD), which may result in permanent disability and death. This study aimed to assess the incidence and predictors of stroke in patients with RHD in the current era of evidence-based recommendations for prevention.
Methods
Consecutive patients with RHD diagnosed by clinical and echocardiographic criteria were selected. A structured clinical and neurological assessment was performed to determine the aetiology and classification of stroke at enrolment. The primary endpoint was an ischaemic cerebrovascular event, which included fatal or non-fatal stroke. Risk of stroke was estimated accounting for competing risks.
Results
A total of 515 patients were enrolled, 438 women (85%), 46±12 years of age. The most frequent valve lesion was mixed mitral (80%). At the time of enrolment, 92 patients (18%) had a prior stroke, with anterior circulation infarction being the most frequent topography (72%). During the mean follow-up of 3.9 years, 27 patients (5.2%) had stroke with the overall incidence of 1.47 strokes per 100 patient-years. Predictors of stroke by the Cox model were prior stroke (adjusted HR 5.395, 95% CI 2.272 to 12.811), age (HR 1.591, 95% CI 1.116 to 2.269) and atrial fibrillation (AF) at baseline (HR 2.945, 95% CI 1.083 to 8.007). By considering death as a competing risk, the effect of AF on stroke risk was attenuated (HR 2.287, 95% CI 0.962 to 5.441).
Conclusions
In this large cohort of patients with RHD, stroke occurred in 5.2% of the patients, which was predicted by age, AF and prior stroke. The effect of AF on stroke risk estimation was influenced by death as competing risk.

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

Heart: 29 Apr 2021; 107:748-754
Vasconcelos M, Vasconcelos L, Ribeiro V, Campos C, ... Teixeira AL, Nunes MCP
Heart: 29 Apr 2021; 107:748-754 | PMID: 33414162
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Abstract

Single high-sensitivity troponin levels to assess patients with potential acute coronary syndromes.

Barnes C, Fatovich DM, Macdonald SPJ, Alcock RF, ... Schultz CJ, Hillis GS
Objective
We tested the hypothesis that patients with a potential acute coronary syndrome (ACS) and very low levels of high-sensitivity cardiac troponin I can be efficiently and safely discharged from the emergency department after a single troponin measurement.
Methods
This prospective cohort study recruited 2255 consecutive patients aged ≥18 years presenting to the Emergency Department, Royal Perth Hospital, Western Australia, with chest pain without high-risk features but requiring the exclusion of ACS. Patients were managed using a guideline-recommended pathway or our novel Single Troponin Accelerated Triage (STAT) pathway. The primary outcome was the percentage of patients discharged in <3 hours. Secondary outcomes included the duration of observation and death or acute myocardial infarction in the next 30 days.
Results
The study enrolled 1131 patients to the standard cohort and 1124 to the STAT cohort. Thirty-eight per cent of the standard cohort were discharged directly from emergency department compared with 63% of the STAT cohort (p<0.001). The median duration of observation was 4.3 (IQR 3.3-7.1) hours in the standard cohort and 3.6 (2.6-5.4) hours in the STAT cohort (p<0.001), with 21% and 38% discharged in <3 hours, respectively (p<0.001). No patients discharged directly from the emergency department died or suffered an acute myocardial infarction within 30 days in either cohort.
Conclusions
Among low-risk patients with a potential ACS, a pathway which incorporates early discharge based on a single very low level of high-sensitivity cardiac troponin increases the proportion of patients discharged directly from the emergency department, reduces length of stay and is safe.
Trial registration number
ACTRN12618000797279.

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

Heart: 29 Apr 2021; 107:721-727
Barnes C, Fatovich DM, Macdonald SPJ, Alcock RF, ... Schultz CJ, Hillis GS
Heart: 29 Apr 2021; 107:721-727 | PMID: 33436490
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Abstract

Racial differences in management and outcomes of acute myocardial infarction during COVID-19 pandemic.

Rashid M, Timmis A, Kinnaird T, Curzen N, ... Gale CP, Mamas M
Objective
There are concerns that healthcare and outcomes of black, Asian and minority ethnic (BAME) communities are disproportionately impacted by the COVID-19 pandemic. We investigated admission rates, treatment and mortality of BAME with acute myocardial infarction (AMI) during COVID-19.
Methods
Using multisource national healthcare records, patients hospitalised with AMI in England during 1 February-27 May 2020 were included in the COVID-19 group, whereas patients admitted during the same period in the previous three consecutive years were included in a pre-COVID-19 group. Multilevel hierarchical regression analyses were used to quantify the changes in-hospital and 7-day mortality in BAME compared with whites.
Results
Of 73 746 patients, higher proportions of BAME patients (16.7% vs 10.1%) were hospitalised with AMI during the COVID-19 period compared with pre-COVID-19. BAME patients admitted during the COVID-19 period were younger, male and likely to present with ST-elevation acute myocardial infarction. COVID-19 BAME group admitted with non-ST-elevation acute myocardial infarction less frequently received coronary angiography (86.1% vs 90.0%, p<0.001) and had a longer median delay to reperfusion (4.1 hours vs 3.7 hours, p<0.001) compared with whites. BAME had higher in-hospital (OR 1.68, 95% CI 1.27 to 2.28) and 7-day mortality (OR 1.81 95% CI 1.31 to 2.19) during COVID-19 compared with pre-COVID-19 period.
Conclusion
In this multisource linked cohort study, compared with whites, BAME patients had proportionally higher hospitalisation rates with AMI, less frequently received guidelines indicated care and had higher early mortality during COVID-19 period compared with pre-COVID-19 period. There is a need to develop clinical pathways to achieve equity in the management of these vulnerable populations.

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

Heart: 29 Apr 2021; 107:734-740
Rashid M, Timmis A, Kinnaird T, Curzen N, ... Gale CP, Mamas M
Heart: 29 Apr 2021; 107:734-740 | PMID: 33685933
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Abstract

Counterpoint: challenges and limitations of transcatheter aortic valve implantation for aortic regurgitation.

Huded CP, Allen KB, Chhatriwalla AK
Transcatheter aortic valve implantation (TAVI) for isolated aortic regurgitation (AR) comprises <1.0% of all TAVI procedures performed in the USA. In this manuscript, we review the challenges, evidence and future directions of TAVI for isolated AR. There are no randomised clinical trials or mid-term data evaluating TAVI for isolated AR, and no commercially available devices are approved for this indication. Challenges in performing TAVI for isolated AR as opposed to aortic stenosis (AS) include: lack of a calcified anchoring zone for valve deployment, large and dynamic size of the aortic annulus and high stroke volume (during systole) and regurgitant volume (during diastole) across the aortic annulus during each cardiac cycle. Observational studies have shown that outcomes of TAVI for AR are worse than outcomes of TAVI for AS. However, newer generation TAVI devices may perform better than older generation devices in patients with AR. Two emerging valves (the JenaValve and the J-Valve) are designed with mechanisms to anchor in a non-calcified annulus, and these valves have shown promise for AR. Data on these devices are limited, and clinical investigation is ongoing. Randomised clinical trials are needed to establish TAVI as a safe and effective treatment for isolated AR.

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Heart: 15 Apr 2021; epub ahead of print
Huded CP, Allen KB, Chhatriwalla AK
Heart: 15 Apr 2021; epub ahead of print | PMID: 33863760
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Abstract

Point: patients with native aortic regurgitation can be treated with transcatheter aortic valve implantation.

Khan SA, Baron SJ
Approximately 2% of people between the ages of 70 and 83 suffer from moderate or greater aortic regurgitation (AR) in the United States. Left untreated, this disease is progressive and fatal; however, up to 8% of patients with AR, who meet the criteria for surgical intervention, do not receive treatment. As such, there is a pressing need to address the lack of treatment options for the thousands of patients with AR who meet a class I indication for aortic valve replacement but who still do not receive surgery. The advent of transcatheter aortic valve implantation (TAVI) has significantly altered the paradigm of treatment for valvular heart disease and is now a well-established therapeutic option for patients with severe aortic stenosis. While transcatheter devices dedicated for the treatment of AR are under investigation, they are not commercially available at this time. Nevertheless, there is a growing body of data that demonstrate acceptable safety and efficacy for the off-label use of current TAVI devices for the treatment of severe AR. Given the dearth of treatment options for inoperable patients with severe AR, available TAVI devices should be considered for this patient population.

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Heart: 15 Apr 2021; epub ahead of print
Khan SA, Baron SJ
Heart: 15 Apr 2021; epub ahead of print | PMID: 33863759
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Abstract

Predictive models for cardiovascular and kidney outcomes in patients with type 2 diabetes: systematic review and meta-analyses.

Buchan TA, Malik A, Chan C, Chambers J, ... Guyatt G, Foroutan F
Objective
To inform a clinical practice guideline (BMJ Rapid Recommendations) considering sodium glucose cotransporter-2 inhibitors and glucagon-like peptide-1 receptor agonists for treatment of adults with type 2 diabetes, we summarised the available evidence regarding the performance of validated risk models on cardiovascular and kidney outcomes in these patients.
Methods
We systematically searched bibliographic databases in January 2020 to identify observational studies evaluating risk models for all-cause and cardiovascular mortality, heart failure (HF) hospitalisations, end-stage kidney disease (ESKD), myocardial infarction (MI) and ischaemic stroke in ambulatory adults with type 2 diabetes. Using a random effects model, we pooled discrimination measures for each model and outcome, separately, and descriptively summarised calibration plots, when available. We used the Prediction Model Risk of Bias Assessment Tool to assess risk of bias of each included study and the Grading of Recommendations, Assessment, Development, and Evaluation approach to evaluate our certainty in the evidence.
Results
Of 22 589 publications identified, 15 observational studies reporting on seven risk models proved eligible. Among the seven models with >1 validation cohort, the Risk Equations for Complications of Type 2 Diabetes (RECODe) had the best calibration in primary studies and the highest pooled discrimination measures for the following outcomes: all-cause mortality (C-statistics 0.75, 95% CI 0.70 to 0.80; high certainty), cardiovascular mortality (0.79, 95% CI 0.75 to 0.84; low certainty), ESKD (0.73, 95% CI 0.52 to 0.94; low certainty), MI (0.72, 95% CI 0.69 to 0.74; moderate certainty) and stroke (0.71, 95% CI 0.68 to 0.74; moderate certainty). This model does not, however, predict risk of HF hospitalisations.
Conclusion
Of available risk models, RECODe proved to have satisfactory calibration in primary validation studies and acceptable discrimination superior to other models, though with high risk of bias in most primary studies.
Trial registration number
CRD42020168351.

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

Heart: 07 Apr 2021; epub ahead of print
Buchan TA, Malik A, Chan C, Chambers J, ... Guyatt G, Foroutan F
Heart: 07 Apr 2021; epub ahead of print | PMID: 33833070
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Abstract

Prognostic implications of left atrial dilation in aortic regurgitation due to bicuspid aortic valve.

Butcher SC, Fortuni F, Kong W, Vollema EM, ... Bax JJ, Delgado V
Objective
To investigate the prognostic value of left atrial volume index (LAVI) in patients with moderate to severe aortic regurgitation (AR) and bicuspid aortic valve (BAV).
Methods
554 individuals (45 (IQR 33-57) years, 80% male) with BAV and moderate or severe AR were selected from an international, multicentre registry. The association between LAVI and the combined endpoint of all-cause mortality or aortic valve surgery was investigated with Cox proportional hazard regression analyses.
Results
Dilated LAVI was observed in 181 (32.7%) patients. The mean indexed aortic annulus, sinus of Valsalva, sinotubular junction and ascending aorta diameters were 13.0±2.0 mm/m2, 19.4±3.7 mm/m2, 16.5±3.8 mm/m2 and 20.4±4.5 mm/m2, respectively. After a median follow-up of 23 (4-82) months, 272 patients underwent aortic valve surgery (89%) or died (11%). When compared with patients with normal LAVI (<35 mL/m2), those with a dilated LAVI (≥35 mL/m2) had significantly higher rates of aortic valve surgery or mortality (43% and 60% vs 23% and 36%, at 1 and 5 years of follow-up, respectively, p<0.001). Dilated LAVI was independently associated with reduced event-free survival (HR=1.450, 95% CI 1.085 to 1.938, p=0.012) after adjustment for LV ejection fraction, aortic root diameter, LV end-diastolic diameter and LV end-systolic diameter.
Conclusions
In this large, multicentre registry of patients with BAV and moderate to severe AR, left atrial dilation was independently associated with reduced event-free survival. The role of this parameter for the risk stratification of individuals with significant AR merits further investigation.

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

Heart: 07 Apr 2021; epub ahead of print
Butcher SC, Fortuni F, Kong W, Vollema EM, ... Bax JJ, Delgado V
Heart: 07 Apr 2021; epub ahead of print | PMID: 33833069
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Abstract

Optimising cardiovascular care of patients with multiple myeloma.

Fontes Oliveira M, Naaktgeboren WR, Hua A, Ghosh AK, ... Hallam S, Manisty C
Multiple myeloma (MM) is the third most common haematological malignancy, with increasing prevalence over recent years. Advances in therapy have improved survival, changing the clinical course of MM into a chronic condition and meaning that management of comorbidities is fundamental to improve clinical outcomes. Cardiovascular (CV) events affect up to 7.5% of individuals with MM, due to a combination of patient, disease and treatment-related factors and adversely impact survival. MM typically affects older people, many with pre-existing CV risk factors or established CV disease, and the disease itself can cause renal impairment, anaemia and hyperviscosity, which exacerabate these further. Up to 15% of patients with MM develop systemic amyloidosis, with prognosis determined by the extent of cardiac involvement. Management of MM generally involves administration of multiple treatment lines over several years as disease progresses, with many drug classes associated with adverse CV effects including high rates of venous and arterial thrombosis alongside heart failure. Recommendations for holistic management of patients with MM now include routine baseline risk stratification including ECG and echocardiography and administration of thromboprophylaxis drugs for patients treated with immunomodulatory drugs. Close surveillance of high-risk patients with collaboration between haematology and cardiology is required, with prompt investigation in the event of CV symptoms, in order to identify and treat complications early. Decisions regarding discontinuation of cardiotoxic therapies should be made in a multidisciplinary setting, taking into account the severity of the complication, prognosis, expected benefits and the availability of effective alternatives.

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Heart: 04 Apr 2021; epub ahead of print
Fontes Oliveira M, Naaktgeboren WR, Hua A, Ghosh AK, ... Hallam S, Manisty C
Heart: 04 Apr 2021; epub ahead of print | PMID: 33820757
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Abstract

Association of cardiovascular health and incident atrial fibrillation in elderly population.

Lee JH, Yang PS, Yu HT, Kim TH, ... Lee MH, Joung B
Objective
To evaluate whether baseline and changes in cardiovascular health (CVH) were related to incident atrial fibrillation (AF) risk in the elderly population.
Methods
From the Korea National Health Insurance Service-Senior cohort, we included 208 598 participants without prior AF (median age: 70 (IQR 66-74) years; 90 916 (43.6%) men) who underwent national health check-ups between 1 January 2005 and 31 December 2012. Using the six metrics of the American Heart Association, participants were categorised as having low, moderate and high CVH.
Results
Over a median follow-up of 7.2 years, 7818 cases of incident AF occurred. In multivariable analysis, moderate (HR: 0.90; 95% CI: 0.86 to 0.94) and high (HR: 0.81; 95% CI: 0.73 to 0.91) CVH status at baseline were associated with a lower risk of incident AF. However, in 109 695 participants with changes in CVH between the first and second check-ups, the direction of change in CVH scores showed no consistent association with future AF incidence. In newly diagnosed participants with AF, the incidence of the composite outcome (stroke, major bleeding and all-cause death) decreased with every 1-point increase in the baseline CVH score (HR: 0.94; 95% CI: 0.89 to 0.99).
Conclusions
In the general elderly population, better baseline CVH metrics were associated with lower incident AF risk. In participants with newly diagnosed AF, better CVH was also associated with lower incidence of future composite outcomes. However, the direction of change in CVH status within 2 years showed an inconsistent influence on incident AF risk.

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Heart: 01 Apr 2021; epub ahead of print
Lee JH, Yang PS, Yu HT, Kim TH, ... Lee MH, Joung B
Heart: 01 Apr 2021; epub ahead of print | PMID: 33811131
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Abstract

Axial flow ventricular assist devices in cardiogenic shock complicating acute myocardial infarction.

McGovern L, Cosgrave J
Cardiogenic shock (CS) remains the leading cause of death in patients hospitalised with acute myocardial infarction with mortality as high as 40%-50% prior to hospital discharge. The failure of inotropic therapy to maintain adequate perfusion and to prevent irreversible end-organ failure has led to attempts to improve outcomes by mechanical circulatory support (MCS) devices. Axial flow ventricular assist devices, namely Impella, are an attractive therapeutic option due to their positive haemodynamic benefits and ease of use. Despite clear beneficial haemodynamic effects, which should significantly impact on the pathophysiology of CS, there are currently no clear data to support their use in the reduction of clinical end points such as cardiac death. This review summarises and critically evaluates the current scientific evidence for the use of axial flow ventricular assist devices and highlights gaps in our understanding. Given such gaps, a consensus multidisciplinary approach, predicated on emphasising timely diagnosis and appropriate use of MCS, is vital to ensure that the right patient is paired with the right device at the right time.

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

Heart: 01 Apr 2021; epub ahead of print
McGovern L, Cosgrave J
Heart: 01 Apr 2021; epub ahead of print | PMID: 33811130
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Abstract

Addition of cystatin C predicts cardiovascular death better than creatinine in intensive care.

Helmersson-Karlqvist J, Lipcsey M, Ärnlöv J, Bell M, ... Dardashti A, Larsson A
Objective
Decreased kidney function increases cardiovascular risk and predicts poor survival. Estimated glomerular filtration rate (eGFR) by creatinine may theoretically be less accurate in the critically ill. This observational study compares long-term cardiovascular mortality risk by the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) creatinine equation; Caucasian, Asian, paediatric and adult cohort (CAPA) cystatin C equation and the CKD-EPI combined creatinine/cystatin C equation.
Methods
The nationwide study includes 22 488 intensive care patients in Uppsala, Karolinska and Lund University Hospitals, Sweden, between 2004 and 2015. Creatinine and cystatin C were analysed with accredited methods at admission. Reclassification and model discrimination with C-statistics was used to compare creatinine and cystatin C for cardiovascular mortality prediction.
Results
During 5 years of follow-up, 2960 (13 %) of the patients died of cardiovascular causes. Reduced eGFR was significantly associated with cardiovascular death by all eGFR equations in Cox regression models. In each creatinine-based GFR category, 17%, 19% and 31% reclassified to a lower GFR category by cystatin C. These patients had significantly higher cardiovascular mortality risk, adjusted HR (95% CI), 1.55 (1.38 to 1.74), 1.76 (1.53 to 2.03) and 1.44 (1.11 to 1.86), respectively, compared with patients not reclassified. Harrell\'s C-statistic for cardiovascular death for cystatin C, alone or combined with creatinine, was 0.73, significantly higher than for creatinine (0.71), p<0.001.
Conclusions
A single cystatin C at admission to the intensive care unit added significant predictive value to creatinine for long-term cardiovascular death risk assessment. Cystatin C, alone or in combination with creatinine, should be used for estimating GFR for long-term risk prediction in critically ill.

© 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: 31 Mar 2021; epub ahead of print
Helmersson-Karlqvist J, Lipcsey M, Ärnlöv J, Bell M, ... Dardashti A, Larsson A
Heart: 31 Mar 2021; epub ahead of print | PMID: 33795382
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Impact:
Abstract

Racial, ethnic and socioeconomic disparities in patients undergoing left atrial appendage closure.

Sparrow R, Sanjoy S, Choi YH, Elgendy IY, ... Mamas MA, Bagur R
Objective
This manuscript aims to explore the impact of race/ethnicity and socioeconomic status on in-hospital complication rates after left atrial appendage closure (LAAC).
Methods
The US National Inpatient Sample was used to identify hospitalisations for LAAC between 1 October 2015 to 31 December 2018. These patients were stratified by race/ethnicity and quartiles of median neighbourhood income. The primary outcome was the occurrence of in-hospital major adverse events, defined as a composite of postprocedural bleeding, cardiac and vascular complications, acute kidney injury and ischaemic stroke.
Results
Of 6478 unweighted hospitalisations for LAAC, 58% were male and patients of black, Hispanic and \'other\' race/ethnicity each comprised approximately 5% of the cohort. Adjusted by the older Americans population, the estimated number of LAAC procedures was 69.2/100 000 for white individuals, as compared with 29.5/100 000 for blacks, 47.2/100 000 for Hispanics and 40.7/100 000 for individuals of \'other\' race/ethnicity. Black patients were ~5 years younger but had a higher comorbidity burden. The primary outcome occurred in 5% of patients and differed significantly between racial/ethnic groups (p<0.001) but not across neighbourhood income quartiles (p=0.88). After multilevel modelling, the overall rate of in-hospital major adverse events was higher in black patients as compared with whites (OR: 1.60, 95% CI 1.22 to 2.10, p<0.001); however, the incidence of acute kidney injury was higher in Hispanics (OR: 2.19, 95% CI 1.52 to 3.17, p<0.001). No significant differences were found in adjusted overall in-hospital complication rates between income quartiles.
Conclusion
In this study assessing racial/ethnic disparities in patients undergoing LAAC, minorities are under-represented, specifically patients of black race/ethnicity. Compared with whites, black patients had higher comorbidity burden and higher rates of in-hospital complications. Lower socioeconomic status was not associated with complication rates.

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

Heart: 31 Mar 2021; epub ahead of print
Sparrow R, Sanjoy S, Choi YH, Elgendy IY, ... Mamas MA, Bagur R
Heart: 31 Mar 2021; epub ahead of print | PMID: 33795381
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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: 31 Mar 2021; epub ahead of print
Packard C, Chapman MJ, Sibartie M, Laufs U, Masana L
Heart: 31 Mar 2021; epub ahead of print | PMID: 33795379
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Impact:
Abstract

Patterns of oral anticoagulation use with cardioversion in clinical practice.

Geurink K, Holmes D, Ezekowitz MD, Pieper K, ... Peterson ED, Pokorney SD
Background
Cardioversion is common among patients with atrial fibrillation (AF). We hypothesised that novel oral anticoagulants (NOAC) used in clinical practice resulted in similar rates of stroke compared with vitamin K antagonists (VKA) for cardioversion.
Methods
Using the Outcomes Registry for Better Informed Treatment of Atrial Fibrillation II, patients with AF who had a cardioversion, follow-up data and an AF diagnosis within 6 months of enrolment were identified retrospectively. Clinical outcomes were compared for patients receiving a NOAC or VKA for 1 year following cardioversion.
Results
Among 13 004 patients with AF, 2260 (17%) underwent cardioversion. 1613 met the inclusion criteria for this analysis. At the time of cardioversion, 283 (17.5%) were receiving a VKA and 1330 (82.5%) a NOAC. A transoesophageal echocardiogram (TOE) was performed in 403 (25%) cardioversions. The incidence of stroke/transient ischaemic attack (TIA) at 30 days was the same for patients having (3.04 per 100 patient-years) or not having (3.04 per 100 patient-years) a TOE (p=0.99). There were no differences in the incidence of death (HR 1.19, 95% CI 0.62 to 2.28, p=0.61), cardiovascular hospitalisation (HR 1.02, 95% CI 0.76 to 1.35, p=0.91), stroke/TIA (HR 1.18, 95% CI 0.30 to 4.74, p=0.81) or bleeding-related hospitalisation (HR 1.29, 95% CI 0.66 to 2.52, p=0.45) at 1 year for patients treated with either a NOAC or VKA.
Conclusions
Cardioversion was a low-risk procedure for patients treated with NOAC, and there were statistically similar rates of stroke/TIA 30 days after cardioversion as for patients treated with VKA. There were no statically significant differences in death, stroke/TIA or major bleeding at 1 year among patients treated with NOAC compared with VKA after cardioversion.

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

Heart: 30 Mar 2021; 107:642-649
Geurink K, Holmes D, Ezekowitz MD, Pieper K, ... Peterson ED, Pokorney SD
Heart: 30 Mar 2021; 107:642-649 | PMID: 32591363
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Impact:
Abstract

Continuous electrocardiography for detecting atrial fibrillation beyond 1 year after stroke in primary care.

Lyckhage LF, Hansen ML, Toft JC, Larsen SL, ... Ali AM, Wienecke T
Background:
and purpose
The diagnostic benefit of using continuous ECG (cECG) for poststroke atrial fibrillation (AF) screening in a primary care setting is unclear. We aimed to assess the diagnostic yield from screening patients who previously had a stroke with a 7-day Holter monitor.
Methods
Patients older than 49 years, naive to AF, with an ischaemic stroke over 1 year before enrolment were included. In a primary care setting, all patients were screened for AF using pulse palpation, 12-lead ECG and 7-day Holter monitoring. Further, NT-proBNP was determined at baseline.
Results
7-day Holter monitoring uncovered AF in 17 of 366 patients (4.6% (95% CI 2.7 to 7.3)). The number needed to screen was 22 patients (14-37). 12-lead ECG uncovered AF in 3 patients (0.82% (95% CI 0.17 to 2.4)), and 122 patients had irregular pulse during pulse palpation (33.5% (95% CI 28.7 to 38.2)). When using 7-day Holter monitoring as reference standard, the sensitivity of pulse palpation and 12-lead ECG was 47% (95% CI 23% to 72%) and 18% (95% CI 4% to 43%). High levels (≥400 pg/mL) of NT-proBNP versus low levels (≤200 pg/mL) were not associated with AF in the univariate analysis nor when adjusted for age (OR 2.4 (95% CI 0.5 to 8.4) and 1.6 (95% CI 0.3 to 6.0)).
Conclusions
A relevant proportion of patients with stroke more than 1 year before inclusion were diagnosed with AF through 7-day Holter monitoring. Given the low sensitivities of pulse palpation and 12-lead ECG, additional cECG may be considered during poststroke primary care 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: 30 Mar 2021; 107:635-641
Lyckhage LF, Hansen ML, Toft JC, Larsen SL, ... Ali AM, Wienecke T
Heart: 30 Mar 2021; 107:635-641 | PMID: 32620555
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Impact:
Abstract

Newly diagnosed diabetes and outcomes after acute myocardial infarction in young adults.

Ding Q, Spatz ES, Lipska KJ, Lin H, ... Bueno H, Krumholz HM
Objective
To examine prevalence and characteristics of newly diagnosed diabetes (NDD) in younger adults hospitalised with acute myocardial infarction (AMI) and investigate whether NDD is associated with health status and clinical outcomes over 12-month post-AMI.
Methods
In individuals (18-55 years) admitted with AMI, without established diabetes, we defined NDD as (1) baseline or 1-month HbA1c≥6.5%; (2) discharge diabetes diagnosis or (3) diabetes medication initiation within 1 month. We compared baseline characteristics of NDD, established diabetes and no diabetes, and their associations with baseline, 1-month and 12-month health status (angina-specific and non-disease specific), mortality and in-hospital complications.
Results
Among 3501 patients in Variation in Recovery: Role of Gender on Outcomes of Young AMI Patients study, 14.5% met NDD criteria. Among 508 patients with NDD, 35 (6.9%) received discharge diagnosis, 91 (17.9%) received discharge diabetes education and 14 (2.8%) initiated pharmacological treatment within 1 month. NDD was more common in non-White (OR 1.58, 95% CI 1.23 to 2.03), obese (OR 1.72, 95% CI 1.39 to 2.12), financially stressed patients (OR 1.27, 95% CI 1.02 to 1.58). Compared with established diabetes, NDD was independently associated with better disease-specific health status and quality of life (p≤0.04). No significant differences were found in unadjusted in-hospital mortality and complications between NDD and established or no diabetes.
Conclusions
NDD was common among adults≤55 years admitted with AMI and was more frequent in non-White, obese, financially stressed individuals. Under 20% of patients with NDD received discharge diagnosis or initiated discharge diabetes education or pharmacological treatment within 1 month post-AMI. NDD was not associated with increased risk of worse short-term health status compared with risk noted for established diabetes.
Trial registration number
NCT00597922.

© 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 Mar 2021; 107:657-666
Ding Q, Spatz ES, Lipska KJ, Lin H, ... Bueno H, Krumholz HM
Heart: 30 Mar 2021; 107:657-666 | PMID: 33082173
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Impact:
Abstract

Cardiogenetics: genetic testing in the diagnosis and management of patients with aortic disease.

Thakker PD, Braverman AC
Thoracic aortic aneurysm and aortic dissection have a potent genetic underpinning with 20% of individuals having an affected relative. Heritable thoracic aortic diseases (HTAD) may be classified as syndromic (including Marfan syndrome, Loeys-Dietz syndrome, vascular Ehlers-Danlos syndrome and others) or non-syndromic (without recognisable phenotypes) and relate to pathogenic variants in multiple genes affecting extracellular matrix proteins, transforming growth factor-beta (TGF-β) signalling and smooth muscle contractile function. Clinical and imaging characteristics may heighten likelihood of an underlying HTAD. HTAD should be investigated in individuals with thoracic aortic aneurysm or aortic dissection, especially when occurring in younger individuals, in those with phenotypic features and in those with a family history of aneurysm disease. Screening family members for aneurysm disease is important. Consultation with a medical geneticist and genetic testing of individuals at increased risk for HTAD is recommended. Medical management and prophylactic aortic surgical thresholds are informed by an accurate clinical and molecular diagnosis.

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

Heart: 30 Mar 2021; 107:619-626
Thakker PD, Braverman AC
Heart: 30 Mar 2021; 107:619-626 | PMID: 33334864
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Impact:
Abstract

Socioeconomic disparities in prehospital factors and survival after out-of-hospital cardiac arrest.

Møller S, Wissenberg M, Starkopf L, Kragholm K, ... Torp-Pedersen C, Gerds TA
Objective
It remains unknown whether patient socioeconomic factors affect interventions and survival after out-of-hospital cardiac arrest (OHCA), and whether a socioeconomic effect on bystander interventions affects survival. Therefore, this study examined patient socioeconomic disparities in prehospital factors and survival.
Methods
From the Danish Cardiac Arrest Registry, patients with OHCA ≥30 years were identified, 2001-2014, and divided into quartiles of household income (highest, high, low, lowest). Associations between income and bystander cardiopulmonary resuscitation (CPR) and 30-day survival with bystander CPR as mediator were analysed by logistic regression and mediation analysis in private witnessed, public witnessed, private unwitnessed and public unwitnessed arrests, adjusted for confounders.
Results
We included 21 480 patients. Highest income patients were younger, had higher education and were less comorbid relative to lowest income patients. They had higher odds for bystander CPR with the biggest difference in private unwitnessed arrests (OR 1.74, 95% CI 1.47 to 2.05). For 30-day survival, the biggest differences were in public witnessed arrests with 26.0% (95% CI 22.4% to 29.7%) higher survival in highest income compared with lowest income patients. Had bystander CPR been the same for lowest income as for highest income patients, then survival would be 25.3% (95% CI 21.5% to 29.0%) higher in highest income compared with lowest income patients, resulting in elimination of 0.79% (95% CI 0.08% to 1.50%) of the income disparity in survival. Similar trends but smaller were observed in low and high-income patients, the other three subgroups and with education instead of income. From 2002 to 2014, increases were observed in both CPR and survival in all income groups.
Conclusion
Overall, lower socioeconomic status was associated with poorer prehospital factors and survival after OHCA that was not explained by patient or cardiac arrest-related factors.

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

Heart: 30 Mar 2021; 107:627-634
Møller S, Wissenberg M, Starkopf L, Kragholm K, ... Torp-Pedersen C, Gerds TA
Heart: 30 Mar 2021; 107:627-634 | PMID: 33419881
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Impact:
Abstract

Tyrosine kinase inhibitors in chronic myeloid leukaemia and emergent cardiovascular disease.

Leong D, Aghel N, Hillis C, Siegal D, ... Pond G, Seow H
Objectives
(1) Describe how the risk of major adverse cardiovascular events (MACE) in individuals with chronic myeloid leukaemia (CML) has evolved; (2) evaluate the risk of MACE associated with the prescription of different CML tyrosine kinase inhibitors (TKI).
Methods
A population-based retrospective study including all patients (n=4238) diagnosed with CML in Ontario, Canada between 1986 and 2017 and and age-matched and sex-matched individuals who received healthcare but who did not have CML (controls: n=42 380). The cohort was divided into those entering before 2001 vs from 2001 onwards (when TKIs were introduced). We developed competing risks models to compare time-to-event in CML cases versus controls. We adjusted for baseline comorbidities and present subdistribution HRs and 95% CIs. The relationship between TKI use and MACE was assessed by logistic regression.
Results
Before 2001 and from 2001 on, patients with CML had a higher crude incidence of MACE than patients without CML (19.8 vs 15.3 and 20.3 vs 12.6 per 1000 person-years, respectively). After adjustment for cardiovascular risk factors, patients with CML had a lower subdistribution hazard for MACE (0.59, 95% CI 0.46 to 0.76) before 2001; but from 2001, the adjusted subdistribution HR for MACE (1.27, 95% CI 0.96 to 1.43) was similar to age-matched and sex-matched patients. The incidence (9.3 vs 13.8 per 1000 person-years) and subdistribution hazard for cardiovascular death (0.43, 95% CI 0.36 to 0.52) were lower in patients with CML than controls before 2001. From 2001 on, the incidence (6.3 vs 5.4 per 1000 person-years) and subdistribution hazard for cardiovascular death (0.99, 95% CI 0.84 to 1.18) were similar to age-matched and sex-matched patients without CML with a higher risk of cerebrovascular events (8.6 vs 5.6 per 1000 person-years; 1.35, 95% CI 1.00 to 1.83) and peripheral arterial events (6.9 vs 3.0 per 1000 person-years; 1.66 95% CI, 1.15 to 2.39) in patients with CML than patients without CML. Compared with imatinib, there was no difference in the risk of MACE among those prescribed dasatinib (OR 0.67, 95% CI 0.41 to 1.10) or nilotinib (OR 1.22, 95% CI 0.70 to 1.97).
Conclusions
In a contemporary CML population, the risk of MACE and cardiovascular death is at least as high as among age-matched and sex-matched patients without CML and may be higher for cerebrovascular and peripheral arterial events. No difference in the risk of MACE between imatinib, dasatinib and nilotinib was observed.

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

Heart: 30 Mar 2021; 107:667-673
Leong D, Aghel N, Hillis C, Siegal D, ... Pond G, Seow H
Heart: 30 Mar 2021; 107:667-673 | PMID: 33419879
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Impact:
Abstract

Coronary revascularisation in patients with ischaemic cardiomyopathy.

Ryan M, Morgan H, Petrie MC, Perera D
Heart failure resulting from ischaemic heart disease is associated with a poor prognosis despite optimal medical treatment. Despite this, patients with ischaemic cardiomyopathy have been largely excluded from randomised trials of revascularisation in stable coronary artery disease. Revascularisation has multiple potential mechanisms of benefit, including the reversal of myocardial hibernation, suppression of ventricular arrhythmias and prevention of spontaneous myocardial infarction. Coronary artery bypass grafting is considered the first-line mode of revascularisation in these patients; however, evidence from the Surgical Treatment of Ischaemic Heart Failure (STICH) trial showed a reduction in mortality, though this only became apparent with extended follow-up due to an excess of early adverse events in the surgical arm. There is currently no randomised controlled trial evidence for percutaneous coronary intervention in patients with ischaemic cardiomyopathy; however, the REVIVED-BCIS2 trial has recently completed recruitment and will address this gap in the evidence. Future directions include (1) clinical trials of revascularisation in patients hospitalised with heart failure, (2) defining the role of viability and ischaemia testing in heart failure, (3) studies to enhance the understanding of the mechanistic effects of revascularisation and (4) generating models to refine pre- and post-revascularisation risk prediction.

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

Heart: 30 Mar 2021; 107:612-618
Ryan M, Morgan H, Petrie MC, Perera D
Heart: 30 Mar 2021; 107:612-618 | PMID: 33436491
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Impact:
Abstract

Recreational substance use among patients with premature atherosclerotic cardiovascular disease.

Mahtta D, Ramsey D, Krittanawong C, Al Rifai M, ... Petersen LA, Virani SS
Objective
Despite an upsurge in the incidence of atherosclerotic cardiovascular diseases (ASCVD) among young adults, the attributable risk of recreational substance use among young patients has been incompletely evaluated. We evaluated the association of all recreational substances with premature and extremely premature ASCVD.
Methods
In a cross-sectional analysis using the 2014-2015 nationwide Veterans Affairs Healthcare database and the Veterans wIth premaTure AtheroscLerosis (VITAL) registry, patients were categorised as having premature, extremely premature or non-premature ASCVD. Premature ASCVD was defined as having first ASCVD event at age <55 years for men and <65 years for women. Extremely premature was defined as having first ASCVD event at age <40 years while non-premature ASCVD was defined as having first ASCVD event at age ≥55 years for men and ≥65 years for women. Patients with premature ASCVD (n=135 703) and those with extremely premature ASCVD (n=7716) were compared against patients with non-premature ASCVD (n=1 112 455). Multivariable logistic regression models were used to study the independent association of all recreational substances with premature and extremely premature ASCVD.
Results
Compared with patients with non-premature ASCVD, patients with premature ASCVD had a higher use of tobacco (62.9% vs 40.6%), alcohol (31.8% vs 14.8%), cocaine (12.9% vs 2.5%), amphetamine (2.9% vs 0.5%) and cannabis (12.5% vs 2.7%) (p<0.01 for all comparisons). In adjusted models, the use of tobacco (OR 1.97, 95% CI 1.94 to 2.00), alcohol (OR 1.50, 95% CI 1.47 to 1.52), cocaine (OR 2.44, 95% CI 2.38 to 2.50), amphetamine (OR 2.74, 95% CI 2.62 to 2.87), cannabis (OR 2.65, 95% CI 2.59 to 2.71) and other drugs (OR 2.53, 95% CI 2.47 to 2.59) was independently associated with premature ASCVD. Patients with polysubstance use had a graded response with the highest risk (~9-fold) of premature ASCVD among patients with use of ≥4 recreational substances. Similar trends were observed among patients with extremely premature ASCVD. Gender interactions with substance use were significant (p-interaction <0.05), with recreational substance use and premature ASCVD showing stronger associations among women than in men with premature ASCVD.
Conclusions
All subgroups of recreational substances were independently associated with a higher likelihood of premature and extremely premature ASCVD. Recreational substance use confers a greater magnitude of risk for premature ASCVD among women. A graded response relationship exists between increasing number of recreational substances used and higher likelihood of early-onset ASCVD.

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

Heart: 30 Mar 2021; 107:650-656
Mahtta D, Ramsey D, Krittanawong C, Al Rifai M, ... Petersen LA, Virani SS
Heart: 30 Mar 2021; 107:650-656 | PMID: 33589427
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Impact:
Abstract

Telomere length is independently associated with all-cause mortality in chronic heart failure.

Romaine SPR, Denniff M, Codd V, Nath M, ... Nelson CP, Samani NJ
Objective
Patients with heart failure have shorter mean leucocyte telomere length (LTL), a marker of biological age, compared with healthy subjects, but it is unclear whether this is of prognostic significance. We therefore sought to determine whether LTL is associated with outcomes in patients with heart failure.
Methods
We measured LTL in patients with heart failure from the BIOSTAT-CHF Index (n=2260) and BIOSTAT-CHF Tayside (n=1413) cohorts. Cox proportional hazards analyses were performed individually in each cohort and the estimates combined using meta-analysis. Our co-primary endpoints were all-cause mortality and heart failure hospitalisation.
Results
In age-adjusted and sex-adjusted analyses, shorter LTL was associated with higher all-cause mortality in both cohorts individually and when combined (meta-analysis HR (per SD decrease in LTL)=1.16 (95% CI 1.08 to 1.24); p=2.66×10-5), an effect equivalent to that of being four years older. The association remained significant after adjustment for the BIOSTAT-CHF clinical risk score to account for known prognostic factors (HR=1.12 (95% CI 1.05 to 1.20); p=1.04×10-3). Shorter LTL was associated with both cardiovascular (HR=1.09 (95% CI 1.00 to 1.19); p=0.047) and non-cardiovascular deaths (HR=1.18 (95% CI 1.05 to 1.32); p=4.80×10-3). There was no association between LTL and heart failure hospitalisation (HR=0.99 (95% CI 0.92 to 1.07); p=0.855).
Conclusion
In patients with heart failure, shorter mean LTL is independently associated with all-cause mortality.

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

Heart: 30 Mar 2021; epub ahead of print
Romaine SPR, Denniff M, Codd V, Nath M, ... Nelson CP, Samani NJ
Heart: 30 Mar 2021; epub ahead of print | PMID: 33789973
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Impact:
Abstract

Increased risk of infective endocarditis after traumatic skin wound.

Ohbe H, Iwagami M, Sasabuchi Y, Yasunaga H
Objective
Current data suggest that a history of traumatic open skin wounds may be a risk factor for infectious endocarditis, with limited evidence. We tested the hypothesis that traumatic skin wound is a risk factor for infectious endocarditis.
Methods
Using the Japan Medical Data Center (JMDC) database (4 650 927 people aged 20-64 years, 2012-2018) and the Kumamoto database (493 414 people aged ≥65 years, 2012-2017), we conducted nested case-control and self-controlled case series (SCCS) analyses.
Results
In the JMDC database, 544 cases hospitalised for infective endocarditis (IE) were matched with 2091 controls; 2.8% of cases and 0.5% of controls were exposed to traumatic skin wounds in the previous 1-4 weeks, with an adjusted OR of 4.31 (95% CI 1.74 to 10.7). In the Kumamoto database, 4.0% (27/670) of cases and 1.1% (29/2581) of controls were exposed to traumatic skin wounds in the previous 1-4 weeks, with an adjusted OR of 4.15 (95% CI 2.04 to 8.46). In the SCCS, the incidence rate ratios for IE were 2.61 (95% CI 1.67 to 4.09), 1.73 (95% CI 1.01 to 2.94), 1.19 (95% CI 0.63 to 2.27) and 1.52 (95% CI 0.82 to 2.74) for the Kumamoto database and 3.78 (95% CI 2.07 to 6.92), 1.58 (95% CI 0.64 to 3.89), 1.60 (95% CI 0.65 to 3.94) and 1.29 (95% CI 0.47 to 3.53) for the JMDC database at 1-4, 5-8, 9-12 and 13-16 weeks after traumatic skin wound, respectively, compared with the baseline period.
Conclusions
This study suggests that traumatic skin wound is a risk factor for IE 1-4 weeks after the wound.

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

Heart: 24 Mar 2021; epub ahead of print
Ohbe H, Iwagami M, Sasabuchi Y, Yasunaga H
Heart: 24 Mar 2021; epub ahead of print | PMID: 33632746
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Impact:
Abstract

Regional variation in cardiovascular magnetic resonance service delivery across the UK.

Keenan NG, Captur G, McCann GP, Berry C, ... Westwood M, Greenwood JP
Objectives
To examine service provision in cardiovascular magnetic resonance (CMR) in the UK. Equitable access to diagnostic imaging is important in healthcare. CMR is widely available in the UK, but there may be regional variations.
Methods
An electronic survey was sent by the British Society of CMR to the service leads of all CMR units in the UK in 2019 requesting data from 2017 and 2018. Responses were analysed by region and interpreted alongside population statistics.
Results
The survey response rate was 100% (82 units). 100 386 clinical scans were performed in 2017 and 114 967 in 2018 (15% 1-year increase; 5-fold 10-year increase compared with 2008 data). In 2018, there were 1731 CMR scans/million population overall, with significant regional variation, for example, 4256 scans/million in London vs 396 scans/million in Wales. Median number of clinical scans per unit was 780, IQR 373-1951, range 98-10 000, with wide variation in mean waiting times (median 41 days, IQR 30-49, range 5-180); median 25 days in London vs 180 days in Northern Ireland). Twenty-five units (30%) reported mean elective waiting times in excess of 6 weeks, and 8 (10%) ≥3 months. There were 351 consultants reporting CMR, of whom 230 (66%) were cardiologists and 121 (34%) radiologists; 81% of units offered a CMR service for patients with pacemakers and defibrillators.
Conclusions
This survey provides a unique, contemporary insight into national CMR delivery with 100% centre engagement. The 10-year growth in CMR usage at fivefold has been remarkable but heterogeneous across the UK, with some regions still reporting low usage or long waiting times which may be of clinical concern.

© 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: 24 Mar 2021; epub ahead of print
Keenan NG, Captur G, McCann GP, Berry C, ... Westwood M, Greenwood JP
Heart: 24 Mar 2021; epub ahead of print | PMID: 33766986
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Impact:
Abstract

Risk of left atrial appendage thrombus and stroke in patients with atrial fibrillation and mitral regurgitation.

Melduni R, Nkomo VT, Wysokinski W, Gersh BJ, ... Oh JK, Lee HC
Objective
To investigate the association of mitral regurgitation (MR) on thromboembolic risk of patients with non-valvular atrial fibrillation (NVAF) undergoing transoesophageal echocardiography (TEE)-guided cardioversion.
Methods
Data for consecutive patients who underwent TEE-guided cardioversion for NVAF between 2000 and 2012 were analysed. MR severity was assessed by Doppler echocardiography and classified as ≤mild, moderate or severe. Left atrial appendage emptying velocities were averaged for five consecutive cycles. Multivariable regression models were used to identify independent predictors of left atrial appendage thrombus (LAAT) and stroke.
Results
2950 patients (age, 69.3±12.2 years, 67% men) were analysed. 2173 (73.7%) had ≤mild MR; 631 (21.4%), moderate MR; and 146 (4.9%), severe MR. Patients with moderate (age, 72.4±10.7 years) and severe (age, 72.8±12.1 years) MR were older than those with ≤mild MR (age, 68.2±12.5 years). The prevalence of LAAT was 1.5% (n=43). CHA2DS2-VASc scores (≤mild MR, 3.0±1.6; moderate MR, 3.5±1.5; severe MR, 3.9±1.5; p<0.001) and heart failure frequency (≤mild MR, 38.4%; moderate MR, 48.0%; severe MR, 69.2%; p<0.001) were increasingly higher with greater MR severity. Multivariable logistic regression analysis showed no association of moderate MR (OR 0.77, 95% CI 0.38 to 1.56) or severe MR (OR 0.55, 95% CI 0.21 to 1.49) with LAAT. During a mean follow-up of 7.3±5.1 years (median 7.5, IQR, 2.7-10.9), 216 patients had an ischaemic stroke. Adjusted Cox regression analysis showed no significant association of moderate MR (HR 1.22, 95% CI 0.88 to 1.68) or severe MR (HR 0.73, 95% CI 0.31 to 1.46) with stroke.
Conclusions
Among patients with NVAF, the presence or severity of MR was not associated with a decreased risk of LAAT or stroke.

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

Heart: 24 Mar 2021; epub ahead of print
Melduni R, Nkomo VT, Wysokinski W, Gersh BJ, ... Oh JK, Lee HC
Heart: 24 Mar 2021; epub ahead of print | PMID: 33766985
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Impact:
Abstract

Safety, efficacy and impact on frailty of mini-invasive radial balloon aortic valvuloplasty.

Tumscitz C, Di Cesare A, Balducelli M, Piva T, ... Campo G, Biscaglia S
Objective
The study was designed to: (1) confirm safety and feasibility of mini-invasive radial balloon aortic valvuloplasty (BAV); (2) assess its impact in terms of quality of life and frailty; and (3) evaluate whether changes in frailty after BAV are associated with death in patients undergoing transcatheter aortic valve implantation (TAVI).
Methods
330 patients undergoing BAV in 16 Italian centres were prospectively included. The primary endpoint was the occurrence of major and minor Valve Academic Research Consortium (VARC)-2 bleeding. Secondary endpoints were scales of quality of life, frailty, evaluated at baseline and 30 days, and their relationship with the occurrence of all-cause death.
Results
BAV was performed by radial access in 314 (95%) patients. No VARC-2 major and six (1.8%) VARC-2 minor bleedings occurred in the study population. Quality of life, as well as frailty status, significantly improved 30 days after BAV. At 1 year, patients undergoing TAVI with baseline essential frailty toolset (EFT) <3 or achieving an EFT <3 after BAV had a comparable occurrence of all-cause death (15% vs 19%, p=0.58). On the contrary, patients with EFT ≥3 at 30 days despite BAV showed the worst prognosis (all-cause death: 40% vs 15% and 19%, p=0.006 and p=0.05, respectively).
Conclusions
Mini-invasive radial BAV is safe, feasible and associated with a low rate of vascular complications. Patients improving EFT 30 days after BAV showed a favourable outcome after TAVI.
Trial registration number
NCT03087552.

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

Heart: 23 Mar 2021; epub ahead of print
Tumscitz C, Di Cesare A, Balducelli M, Piva T, ... Campo G, Biscaglia S
Heart: 23 Mar 2021; epub ahead of print | PMID: 33627400
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Impact:
Abstract

Hospital variation of 30-day readmission rate following transcatheter aortic valve implantation.

Ando T, Ashraf S, Kuno T, Briasoulis A, ... Grines C, Malik A
Objectives
Thirty-day readmission rate is one of the hospital quality metrics. Outcomes of transcatheter aortic valve implantation (TAVI) have improved significantly, but it remains unclear whether hospital-level variance in 30-day readmission rate exists in the contemporary TAVI era.
Methods
From the 2017 US Nationwide Readmission Database, endovascular TAVI were identified. The unadjusted 30-day readmission rate and 30-day risk-standardised readmission rate (RSRR) were calculated and we then conducted model testing to determine the relative contribution of hospital characteristics, patient-level covariates and economic status to the variation in readmission rates observed between the hospitals.
Results
A total of 44 899 TAVI from 338 hospitals were identified. The range of unadjusted 30-day readmission rate and 30-day RSRR was 2.0%-33.3% and 9.4%-15.3%, respectively. Median 30-day RSRR was 11.8% and there was a significant hospital-level variation (median OR 1.22, 95% CI 1.16 to 1.32, p<0.01) and this was similar in both readmissions caused due to major cardiac and non-cardiac conditions. Patient, hospital and economic factors accounted for 9.6%, 1.9% and 3.8% of the variability in hospital readmission rate, respectively.
Conclusions
There was significant hospital-level variation in 30-day RSRR following TAVI. Further measures are required to mitigate this variance in the readmission rate.

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

Heart: 23 Mar 2021; epub ahead of print
Ando T, Ashraf S, Kuno T, Briasoulis A, ... Grines C, Malik A
Heart: 23 Mar 2021; epub ahead of print | PMID: 33627399
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Impact:
Abstract

P2Y12 inhibitor monotherapy after coronary stenting according to type of P2Y12 inhibitor.

Kim J, Jang WJ, Lee WS, Choi KH, ... Rha SW, Hahn JY
Objective
To compare P2Y12 inhibitor monotherapy after 3-month dual antiplatelet therapy (DAPT) with 12-month DAPT according to the type of P2Y12 inhibitor in patients undergoing percutaneous coronary intervention (PCI).
Methods
The Smart Angioplasty Research Team: Comparison Between P2Y12 Antagonist Monotherapy vs Dual Antiplatelet Therapy in Patients Undergoing Implantation of Coronary Drug-Eluting Stents (SMART-CHOICE) randomised trial compared 3-month DAPT followed by P2Y12 inhibitor monotherapy with 12-month DAPT. In this trial, 2993 patients undergoing successful PCI with drug-eluting stent were enrolled in Korea. As a prespecified analysis, P2Y12 inhibitor monotherapy after 3-month DAPT versus 12-month DAPT were compared among patients receiving clopidogrel and those receiving potent P2Y12 inhibitor (ticagrelor or prasugrel), respectively. The primary endpoint was a composite of all-cause death, myocardial infarction or stroke at 12 months after the index procedure.
Results
Among 2993 patients (mean age 64 years), 58.2% presented with acute coronary syndrome. Clopidogrel was prescribed in 2312 patients (77.2%) and a potent P2Y12 inhibitor in 681 (22.8%). There were no significant differences in the primary endpoint between the P2Y12 inhibitor monotherapy group and the DAPT group among patients receiving clopidogrel (3.0% vs 3.0%; HR: 1.02; 95% CI 0.64 to 1.65; p=0.93) as well as among patients receiving potent P2Y12 inhibitors (2.4% vs 0.7%; HR: 3.37; 95% CI 0.77 to 14.78; p=0.11; interaction p=0.1). Among patients receiving clopidogrel, P2Y12 inhibitor monotherapy compared with DAPT showed consistent treatment effects across various subgroups for the primary endpoint. Among patients receiving potent P2Y12 inhibitors, the rate of bleeding (Bleeding Academic Research Consortium types 2- 5) was significantly lower in the P2Y12 inhibitor monotherapy group than in the DAPT group (1.5% vs 5.0%; HR: 0.33; 95% CI 0.12 to 0.87; p=0.03).
Conclusions
Compared with 12-month DAPT, clopidogrel monotherapy after 3-month DAPT showed comparable cardiovascular outcomes in patients undergoing PCI.
Trial registration number
NCT02079194.

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

Heart: 22 Mar 2021; epub ahead of print
Kim J, Jang WJ, Lee WS, Choi KH, ... Rha SW, Hahn JY
Heart: 22 Mar 2021; epub ahead of print | PMID: 33758008
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Impact:
Abstract

Relative survival after aortic valve surgery in patients with bicuspid aortic valves.

Glaser N, Jackson V, Eriksson P, Sartipy U, Franco-Cereceda A
Objectives
The objective of this cohort study was to analyse long-term relative survival in patients with bicuspid aortic valve (BAV) who underwent aortic valve surgery.
Methods
We studied 865 patients with BAVs who participated in three prospective cohort studies of elective, open-heart, aortic valve surgery at the Karolinska University Hospital, Stockholm, Sweden, between 2007 and 2020. The expected survival for the age, sex and calendar year-matched general Swedish population was obtained from the Human Mortality Database. The Ederer II method was used to calculate relative survival, which was used as an estimate of cause-specific survival.
Results
No differences were found in the observed versus expected survival at 1, 5, 10 or 12 years: 99%, 94%, 83% and 76% vs 99%, 93%, 84% and 80%, respectively. The relative survival at 1, 5, 10 and 12 years was 100% (95% CI 99% to 100%), 101% (95% CI 99% to 103%), 99% (95% CI 95% to 103%) and 95% (95% CI 87% to 102%), respectively. The relative survival at the end of follow-up tended to be lower for women than men (86% vs 95%). The mean follow-up was 6.3 years (maximum 13.3 years).
Conclusions
The survival of patients with BAV following aortic valve surgery was excellent and similar to that of the general population. Our results suggest that the timing of surgery according to current guidelines is correct and provide robust long-term survival rates, as well as important information about the natural history of BAV in patients following aortic valve surgery.

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

Heart: 22 Mar 2021; epub ahead of print
Glaser N, Jackson V, Eriksson P, Sartipy U, Franco-Cereceda A
Heart: 22 Mar 2021; epub ahead of print | PMID: 33622679
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Impact:
Abstract

Metabolic phenotyping and cardiovascular disease: an overview of evidence from epidemiological settings.

Iliou A, Mikros E, Karaman I, Elliott F, ... Tzoulaki I, Elliott P
Metabolomics, the comprehensive measurement of low-molecular-weight molecules in biological fluids used for metabolic phenotyping, has emerged as a promising tool to better understand pathways underlying cardiovascular disease (CVD) and to improve cardiovascular risk stratification. Here, we present the main methodologies for metabolic phenotyping, the methodological steps to analyse these data in epidemiological settings and the associated challenges. We discuss evidence from epidemiological studies linking metabolites to coronary heart disease and stroke. These studies indicate the systemic nature of CVD and identify associated metabolic pathways such as gut microbial cometabolism, branched-chain amino acids, glycerophospholipid and cholesterol metabolism, as well as activation of inflammatory processes. Integration of metabolomic with genomic data can provide new evidence for involved biochemical pathways and potential for causality using Mendelian randomisation. The clinical utility of metabolic biomarkers for cardiovascular risk stratification in healthy individuals has not yet been established. As sample sizes with high-dimensional molecular data increase in epidemiological settings, integration of metabolomic data across studies and platforms with other molecular data will lead to new understanding of the metabolic processes underlying CVD and contribute to identification of potentially novel preventive and pharmacological targets. Metabolic phenotyping offers a powerful tool in the characterisation of the molecular signatures of CVD, paving the way to new mechanistic understanding and therapies, as well as improving risk prediction of CVD patients. However, there are still challenges to face in order to contribute to clinically important improvements in CVD.

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

Heart: 18 Mar 2021; epub ahead of print
Iliou A, Mikros E, Karaman I, Elliott F, ... Tzoulaki I, Elliott P
Heart: 18 Mar 2021; epub ahead of print | PMID: 33608305
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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: 18 Mar 2021; epub ahead of print
Gaur L, Cedars A, Diller GP, Kutty S, Orwat S
Heart: 18 Mar 2021; epub ahead of print | PMID: 33741578
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Impact:
Abstract

Breathing training improves exercise capacity in patients with tetralogy of Fallot: a randomised trial.

Hock J, Remmele J, Oberhoffer R, Ewert P, Hager A
Objective
Patients with tetralogy of Fallot (ToF) have limited pulmonary blood flow before corrective surgery and ongoing dysfunction of the pulmonary valve and right ventricle throughout life leading to lower exercise capacity and lung volumes in many patients. Inhalation training can increase lung volumes, improve pulmonary blood flow and consequently exercise capacity. This study tests whether home-based daily breathing training improves exercise capacity and lung volumes.
Methods
From February 2017 to November 2018, 60 patients (14.7±4.8 years, 39% female) underwent spirometry (forced vital capacity (FVC); forced expiratory volume in 1 s (FEV1)), cardiopulmonary exercise testing (peak oxygen uptake (peak [Formula: see text]O2)) and breathing excursion measurement. They were randomised into immediate breathing exercise or control group (CG) and re-examined after 6 months. The CG started their training afterwards and were re-examined after further 6 months. Patients trained with an inspiratory volume-oriented breathing device and were encouraged to exercise daily. The primary endpoint of this study was the change in peak [Formula: see text]O2. Results are expressed as mean±SEM (multiple imputations).
Results
In the first 6 months (intention to treat analysis), the training group showed a more favourable change in peak [Formula: see text]O2 (Δ0.5±0.6 vs -2.3±0.9 mL/min/kg, p=0.011), FVC (Δ0.18±0.03 vs 0.08±0.03 L, p=0.036) and FEV1 (Δ0.14±0.03 vs -0.00±0.04 L, p=0.007). Including the delayed training data from the CG (n=54), this change in peak [Formula: see text]O2 correlated with self-reported weekly training days (r=0.282, p=0.039).
Conclusions
Daily inspiratory volume-oriented breathing training increases dynamic lung volumes and slows down deconditioning in peak [Formula: see text]O2 in young patients with repaired ToF.

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

Heart: 17 Mar 2021; epub ahead of print
Hock J, Remmele J, Oberhoffer R, Ewert P, Hager A
Heart: 17 Mar 2021; epub ahead of print | PMID: 33737455
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Impact:
Abstract

Anti-interleukin 1 agents for the treatment of recurrent pericarditis: a systematic review and meta-analysis.

Imazio M, Andreis A, Piroli F, Lazaros G, ... Klein AL, Brucato A
Aims
Corticosteroid-dependent and colchicine-resistant recurrent pericarditis (RP) is a challenging management problem, in which conventional anti-inflammatory therapy (nonsteroidal anti-inflammatory drugs, colchicine, corticosteroids) is unable to control the disease. Recent data suggest a potential role for anti-interleukin-1 (IL-1) agents for this condition. This study was designed to assess the safety and efficacy of anti-IL-1 agents in this setting.
Methods
We performed a systematic review and meta-analysis of randomised controlled trials and observational studies assessing pericarditis recurrences and drug-related adverse events in patients receiving anti-IL-1 drugs for pericarditis.
Results
The meta-analysis assessed 7 studies including 397 pooled patients with RP. The median age was 42 years, 60% were women and the aetiology was idiopathic in 87%. After a median follow-up of 14 months (IQR,12-39), patients receiving anti-IL-1 agents (anakinra or rilonacept) had a significantly reduction in pericarditis recurrences (incidence rate ratio 0.06, 95% CI 0.03 to 0.14), compared with placebo and/or standard medical therapy. Anti-IL-1 agents were associated with increased risk of adverse events compared with placebo (risk ratio (RR) 5.38, 95% CI 2.08 to 13.92): injection-site reactions occurred in 15/41 (36.6%) vs none (RR 14.98, 95% CI 2.09 to 107.09), infections occurred in 13/51 (25.5%) vs 3/41 (7.3%; RR 3.65, 95% CI 1.23 to 10.85). Anti-IL-1 agents were not associated with increased risk of severe adverse events.
Conclusions
In patients with RP, anti-IL-1 agents (anakinra and rilonacept) are efficacious for prevention of recurrences, without severe adverse events.

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

Heart: 17 Mar 2021; epub ahead of print
Imazio M, Andreis A, Piroli F, Lazaros G, ... Klein AL, Brucato A
Heart: 17 Mar 2021; epub ahead of print | PMID: 33737453
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Impact:
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: 14 Mar 2021; epub ahead of print
Stein-Merlob AF, Rothberg MV, Ribas A, Yang EH
Heart: 14 Mar 2021; epub ahead of print | PMID: 33722826
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Impact:
Abstract

Sexism experienced by consultant cardiologists in the United Kingdom.

Jaijee SK, Kamau-Mitchell C, Mikhail GW, Hendry C
Objectives
The aims were to compare the frequency with which male and female cardiologists experience sexism and to explore the types of sexism experienced in cardiology.
Methods
A validated questionnaire measuring experiences of sexism and sexual harassment was distributed online to 890 UK consultant cardiologists between March and May 2018. χ2 tests and pairwise comparisons with a Bonferroni correction for multiple analyses compared the experiences of male and female cardiologists.
Results
174 cardiologists completed the survey (24% female; 76% male). The survey showed that 61.9% of female cardiologists have experienced discrimination of any kind, mostly related to gender and parenting, compared with 19.7% of male cardiologists. 35.7% of female cardiologists experienced unwanted sexual comments, attention or advances from a superior or colleague, compared with 6.1% of male cardiologists. Sexual harassment affected the professional confidence of female cardiologists more than it affected the confidence of male cardiologists (42.9% vs 3.0%), including confidence with colleagues (38% vs 10.6%) and patients (23.9% vs 4.6%). 33.3% of female cardiologists felt that sexism hampered opportunities for professional advancement, compared with 2.3% of male cardiologists.
Conclusion
Female cardiologists in the UK experience more sexism and sexual harassment than male cardiologists. Sexism impacts the career progression and professional confidence of female cardiologists more, including their confidence when working with patients and colleagues. Future research is urgently needed to test interventions against sexism in cardiology and to protect the welfare of female cardiologists at work.

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

Heart: 14 Mar 2021; epub ahead of print
Jaijee SK, Kamau-Mitchell C, Mikhail GW, Hendry C
Heart: 14 Mar 2021; epub ahead of print | PMID: 33722825
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Impact:
Abstract

Prasugrel versus ticagrelor in patients with myocardial infarction undergoing percutaneous coronary intervention.

Venetsanos D, Träff E, Erlinge D, Hagström E, ... Jernberg T, Alfredsson J
Objective
The comparative efficacy and safety of prasugrel and ticagrelor in patients with myocardial infarction (MI) treated with percutaneous coronary intervention (PCI) remain unclear. We aimed to investigate the association of treatment with clinical outcomes.
Methods
In the SWEDEHEART (Swedish Web-system for enhancement and development of evidence-based care in heart disease evaluated according to recommended therapies) registry, all patients with MI treated with PCI and discharged on prasugrel or ticagrelor from 2010 to 2016 were included. Outcomes were 1-year major adverse cardiac and cerebrovascular events (MACCE, death, MI or stroke), individual components and bleeding. Multivariable adjustment, inverse probability of treatment weighting (IPTW) and propensity score matching (PSM) were used to adjust for confounders.
Results
We included 37 990 patients, 2073 in the prasugrel group and 35 917 in the ticagrelor group. Patients in the prasugrel group were younger, more often admitted with ST elevation MI and more likely to have diabetes. Six to twelve months after discharge, 20% of patients in each group discontinued the P2Y12 receptor inhibitor they received at discharge. The risk for MACCE did not significantly differ between prasugrel-treated and ticagrelor-treated patients (adjusted HR 1.03, 95% CI 0.86 to 1.24). We found no significant difference in the adjusted risk for death, recurrent MI or stroke alone between the two treatments. There was no significant difference in the risk for bleeding with prasugrel versus ticagrelor (2.5% vs 3.2%, adjusted HR 0.92, 95% CI 0.69 to 1.22). IPTW and PSM analyses confirmed the results.
Conclusion
In patients with MI treated with PCI, prasugrel and ticagrelor were associated with similar efficacy and safety during 1-year follow-up.

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

Heart: 11 Mar 2021; epub ahead of print
Venetsanos D, Träff E, Erlinge D, Hagström E, ... Jernberg T, Alfredsson J
Heart: 11 Mar 2021; epub ahead of print | PMID: 33712510
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Impact:
Abstract

Norepinephrine, plasma renin activity and cardiovascular mortality in systolic heart failure.

Aimo A, Prontera C, Passino C, Emdin M, Vergaro G
Objective
We analysed the circulating levels and prognostic value of N-terminal pro-B-type natriuretic peptide (NT-proBNP), norepinephrine (NE), epinephrine (E), plasma renin activity (PRA) and aldosterone in patients with systolic heart failure (HF) receiving therapies that target the sympathetic system and the renin-angiotensin-aldosterone axis.
Methods
We retrieved data from consecutive HF outpatients with left ventricular ejection fraction (LVEF) <50% and available neurohormones, evaluated at a tertiary referral centre for HF from 1999 to 2016.
Results
Patients (n=1477) were aged 66±13 years, 75% were men, median LVEF was 32% (IQR 25-38), 77% had LVEF <40% and 44% ischaemic HF. At the time of sampling, 69% were on beta-blockers, 75% on ACE inhibitors/angiotensin receptor blockers and 48% on mineralocorticoid receptor antagonists vs 88%, 87% and 66%, respectively, after therapy optimisation. Median NT-proBNP, NE, E, PRA and aldosterone were 1441 ng/L, 494 ng/L, 30 ng/L, 1.2 ng/mL/hour and 130 ng/dL, respectively. Over a 4.8-year follow-up (2.4-8.2), 376 patients died from cardiovascular causes (26%). NT-proBNP and PRA predicted cardiovascular mortality after adjusting for all other univariable predictors. The risk of cardiovascular death increased by 8% or 7% per each doubling of PRA in 2 models considering therapies at the time of sampling or after therapy optimisation. PRA improved metrics of reclassification and discrimination, and independently predicted outcome even in the LVEF <40% subgroup.
Conclusions
In patients with HF with LVEF <50% or <40%, PRA shows independent prognostic significance from a model that includes NT-proBNP, and might represent an additive tool for risk stratification.

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

Heart: 11 Mar 2021; epub ahead of print
Aimo A, Prontera C, Passino C, Emdin M, Vergaro G
Heart: 11 Mar 2021; epub ahead of print | PMID: 33712509
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Impact:
Abstract

Incidence, predictors and mortality risk of new heart failure in patients hospitalised with atrial fibrillation.

Weber C, Hung J, Hickling S, Nedkoff L, ... Li I, Briffa TG
Objective
To determine the incidence, risk predictors and relative mortality risk of incident heart failure (HF) in patients following atrial fibrillation (AF) hospitalisation.
Methods
The Western Australian Hospitalisation Morbidity Data Collection was used to identify patients aged 25-94 years with index (first-in-period) AF hospitalisation, but without a prior HF admission, between 2000 and 2013. We evaluated the risk of incident HF hospitalisation within 3 years after AF admission, and the impact of HF hospitalisation on all-cause mortality.
Results
The cohort comprised 52 447 patients, 57.5% men, with a median age of 73.1 (IQR 63.2-80.8) years. At 3 years after AF discharge, the cumulative incidence of HF (n=6153) was 11.7% (95% CI 11.5% to 12.0%) and all-cause death (n=9702) was 18.5% (95% CI 18.2% to 18.8%). Independent predictors of incident HF included advancing age, any history of myocardial infarction (MI), peripheral vascular disease, valvular heart disease, chronic kidney disease, chronic obstructive pulmonary disease, hypertension, diabetes, obesity and excessive alcohol use (all p<0.001). Patients hospitalised for first-ever HF compared with those without HF hospitalisation had an adjusted HR of 3.3 (95% CI 3.1 to 3.4) for all-cause mortality (p<0.001). Independent predictors of HF were also shared with those for mortality, with the exception of hypertension.
Conclusion
Hospitalisation for new HF is common in patients with AF and independently associated with a 3-fold hazard for death. The clinical predictors of incident HF emphasise the importance of integrated management of common comorbid conditions and lifestyle risk factors in patients with AF to reduce their morbidity and mortality.

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

Heart: 10 Mar 2021; epub ahead of print
Weber C, Hung J, Hickling S, Nedkoff L, ... Li I, Briffa TG
Heart: 10 Mar 2021; epub ahead of print | PMID: 33707226
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Impact:
Abstract

Association between routine measures of graft function and mortality in heart transplant recipients.

Foroutan F, Malik A, Nelson LMS, Steve CF, ... Ross H, Alba AC
Objective
To date, long-term graft dysfunction, an important cause of death after heart transplantation, has been defined as a left ventricular ejection fraction (LVEF) of ≤40% or right atrial pressure (RAP) of ≥15 mm Hg. Empirical associations between measures of cardiac function and mortality post-transplant remain, however, unestablished.
Methods
We conducted a retrospective two-centre cohort study of consecutive adults who underwent heart transplant between 2002 and 2017. We evaluated the association between LVEF and RAP and mortality, including rejection and cardiac allograft vasculopathy as additional time-dependent covariates using Cox proportional hazard models. We applied restricted cubic splines to both LVEF and RAP.
Results
Of 590 eligible heart transplant recipients, of whom 72% were male with a mean age of 49 years, 410 received their transplant at Toronto General Hospital and 180 at Rigshospitalet. We observed a 5% absolute risk increase for 1-year mortality, from 11% to 16%, when the LVEF dropped to 53% (HR 1.71 for LVEF of 53% compared with 60%, 95% CI 1.36 to 2.14) or when the RAP increased to 12 mm Hg (HR 1.49 for RAP of 12 mm Hg compared with 5 mm Hg, 95% CI 1.04 to 2.13).
Conclusion
In this study, we observed that small changes in graft function at any time post-transplant are associated with an increased mortality. Our results suggest that the current definition of graft dysfunction may underestimate patient risk of adverse outcomes.

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

Heart: 10 Mar 2021; epub ahead of print
Foroutan F, Malik A, Nelson LMS, Steve CF, ... Ross H, Alba AC
Heart: 10 Mar 2021; epub ahead of print | PMID: 33707225
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Impact:
Abstract

Improving the diagnosis of heart failure in patients with atrial fibrillation.

Bunting KV, Gill SK, Sitch A, Mehta S, ... Kotecha D, RAte control Therapy Evaluation in permanent Atrial Fibrillation (RATE-AF) trial group
Objective
To improve the echocardiographic assessment of heart failure in patients with atrial fibrillation (AF) by comparing conventional averaging of consecutive beats with an index-beat approach, whereby measurements are taken after two cycles with similar R-R interval.
Methods
Transthoracic echocardiography was performed using a standardised and blinded protocol in patients enrolled in the RATE-AF (RAte control Therapy Evaluation in permanent Atrial Fibrillation) randomised trial. We compared reproducibility of the index-beat and conventional consecutive-beat methods to calculate left ventricular ejection fraction (LVEF), global longitudinal strain (GLS) and E/e\' (mitral E wave max/average diastolic tissue Doppler velocity), and assessed intraoperator/interoperator variability, time efficiency and validity against natriuretic peptides.
Results
160 patients were included, 46% of whom were women, with a median age of 75 years (IQR 69-82) and a median heart rate of 100 beats per minute (IQR 86-112). The index-beat had the lowest within-beat coefficient of variation for LVEF (32%, vs 51% for 5 consecutive beats and 53% for 10 consecutive beats), GLS (26%, vs 43% and 42%) and E/e\' (25%, vs 41% and 41%). Intraoperator (n=50) and interoperator (n=18) reproducibility were both superior for index-beats and this method was quicker to perform (p<0.001): 35.4 s to measure E/e\' (95% CI 33.1 to 37.8) compared with 44.7 s for 5-beat (95% CI 41.8 to 47.5) and 98.1 s for 10-beat (95% CI 91.7 to 104.4) analyses. Using a single index-beat did not compromise the association of LVEF, GLS or E/e\' with natriuretic peptide levels.
Conclusions
Compared with averaging of multiple beats in patients with AF, the index-beat approach improves reproducibility and saves time without a negative impact on validity, potentially improving the diagnosis and classification of heart failure in patients with AF.

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

Heart: 09 Mar 2021; epub ahead of print
Bunting KV, Gill SK, Sitch A, Mehta S, ... Kotecha D, RAte control Therapy Evaluation in permanent Atrial Fibrillation (RATE-AF) trial group
Heart: 09 Mar 2021; epub ahead of print | PMID: 33692093
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Impact:
Abstract

Clinical outcome of COVID-19 in patients with adult congenital heart disease.

Schwerzmann M, Ruperti-Repilado FJ, Baumgartner H, Bouma B, ... Greutmann M, EPOCH
Aims
Patients with adult congenital heart disease (ACHD) are a potentially vulnerable patient cohort in case of COVID-19. Some cardiac defects may be associated with a poor COVID-19 outcome. Risk estimation in ACHD is currently based on expert opinion. The aim of this study was to collect clinical outcome data and to identify risk factors for a complicated course of COVID-19 in patients with ACHD.
Methods
Twenty-five ACHD centres in nine European countries participated in the study. Consecutive patients with ACHD diagnosed with COVID-19 presenting to one of the participating centres between 27 March and 6 June 2020 were included. A complicated disease course was defined as hospitalisation for COVID-19 requiring non-invasive or invasive ventilation and/or inotropic support, or a fatal outcome.
Results
Of 105 patients with a mean age of 38±13 years (58% women), 13 had a complicated disease course, of whom 5 died. In univariable analysis, age (OR 1.3, 95% CI 1.1 to 1.7, per 5 years), ≥2 comorbidities (OR 7.1, 95% CI 2.1 to 24.5), body mass index of >25 kg/m2 (OR 7.2, 95% CI 1.9 to 28.3) and cyanotic heart disease (OR 13.2, 95% CI 2.5 to 68.4) were associated with a complicated disease course. In a multivariable logistic regression model, cyanotic heart disease was the most important predictor (OR 60.0, 95% CI 7.6 to 474.0).
Conclusions
Among patients with ACHD, general risk factors (age, obesity and multiple comorbidities) are associated with an increased risk of complicated COVID-19 course. Congenital cardiac defects at particularly high risk were cyanotic lesions, including unrepaired cyanotic defects or Eisenmenger syndrome.

© 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: 07 Mar 2021; epub ahead of print
Schwerzmann M, Ruperti-Repilado FJ, Baumgartner H, Bouma B, ... Greutmann M, EPOCH
Heart: 07 Mar 2021; epub ahead of print | PMID: 33685931
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Abstract

Endovascular repair for abdominal aortic aneurysms.

Debono S, Nash J, Tambyraja AL, Newby DE, Forsythe RO
Management of abdominal aortic aneurysms has been the subject of rigorous scientific scrutiny. Prevalence studies have directed the formation of screening programmes, and observational studies and randomised controlled trials have defined aneurysm growth and treatment thresholds. Pre-emptive intervention with traditional open surgical repair has been the bedrock of improving long-term outcome and survival in patients with abdominal aortic aneurysms but it is associated with a significant procedural morbidity and mortality. Endovascular aneurysm repair (EVAR) has substantially reduced these early complications and has been associated with promising results in both elective and emergency aneurysm repair. However, the technique has brought its own unique complications, endoleaks. An endoleak is the presence of blood flow within the aneurysm sac but outside the EVAR graft. Although in randomised control trials EVAR was associated with a reduced early mortality compared with open repair, its longer-term morbidity and mortality was higher because endoleak development is associated with a higher risk of rupture. These endoleak complications have necessitated the development of postoperative imaging surveillance and re-intervention. These contrasting benefits and risks inform the selection of the mode of repair and are heavily influenced by individual patient factors. An improved strategy to predict endoleak development could further help direct treatment choice for patients and improve both early and late outcomes. This article reviews current EVAR practice, recent updates in clinical practice guidelines and the potential future developments to facilitate the selection of mode of aneurysm repair.Trial registration number: ClinicalTrials.gov NCT04577716.

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

Heart: 03 Mar 2021; epub ahead of print
Debono S, Nash J, Tambyraja AL, Newby DE, Forsythe RO
Heart: 03 Mar 2021; epub ahead of print | PMID: 33674354
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Abstract

Implantable cardiac defibrillator events in patients with arrhythmogenic right ventricular cardiomyopathy.

Woźniak O, Borowiec K, Konka M, Cicha-Mikołajczyk A, ... Poślednik K, Biernacka EK
Objective
Arrhythmogenic right ventricular cardiomyopathy (ARVC) is associated with a risk of sudden cardiac death. Optimal risk stratification is still under debate. The main purpose of this long-term, single-centre observation was to analyse predictors of appropriate and inappropriate implantable cardioverter-defibrillator (ICD) interventions in the population of patients with ARVC with a high risk of life-threatening arrhythmias.
Methods
The study comprised 65 adult patients (median age 40 years, 48 men) with a definite diagnosis of ARVC who received ICD over a time span of 20 years in primary (40%) or secondary (60%) prevention of sudden cardiac death. The study endpoints were first appropriate and inappropriate ICD interventions (shock or antitachycardia pacing) after device implantation.
Results
During a median follow-up of 7.75 years after ICD implantation, nine patients died and six individuals underwent heart transplantation. Appropriate ICD interventions occurred in 43 patients (66.2%) and inappropriate ICD interventions in 18 patients (27.7%). Multivariable analysis using cause-specific hazard model identified three predictors of appropriate ICD interventions: right ventricle dysfunction (cause-specific HR 2.85, 95% CI 1.56 to 5.21, p<0.001), age <40 years at ICD implantation (cause-specific HR 2.37, 95% CI 1.13 to 4.94, p=0.022) and a history of sustained ventricular tachycardia (cause-specific HR 2.55, 95% CI 1.16 to 5.63, p=0.020). Predictors of inappropriate ICD therapy were not found. Complications related to ICD implantation occurred in 12 patients.
Conclusions
Right ventricle dysfunction, age <40 years and a history of sustained ventricular tachycardia were predictors of appropriate ICD interventions in patients with ARVC. The results may be used to improve risk stratification before ICD implantation.

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

Heart: 03 Mar 2021; epub ahead of print
Woźniak O, Borowiec K, Konka M, Cicha-Mikołajczyk A, ... Poślednik K, Biernacka EK
Heart: 03 Mar 2021; epub ahead of print | PMID: 33674353
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Impact:
Abstract

Community prevalence, mechanisms and outcome of mitral or tricuspid regurgitation.

Cahill TJ, Prothero A, Wilson J, Kennedy A, ... Prendergast BD, Myerson SG
Objective
The study aims were (1) to identify the community prevalence of moderate or greater mitral or tricuspid regurgitation (MR/TR), (2) to compare subjects identified by population screening with those with known valvular heart disease (VHD), (3) to understand the mechanisms of MR/TR and (4) to assess the rate of valve intervention and long-term outcome.
Methods
Adults aged ≥65 years registered at seven family medicine practices in Oxfordshire, UK were screened for inclusion (n=9504). Subjects with known VHD were identified from hospital records and those without VHD invited to undergo transthoracic echocardiography (TTE) within the Oxford Valvular Heart Disease Population Study (OxVALVE). The study population ultimately comprised 4755 subjects. The severity and aetiology of MR and TR were assessed by integrated comprehensive TTE assessment.
Results
The prevalence of moderate or greater MR and TR was 3.5% (95% CI 3.1 to 3.8) and 2.6% (95% CI 2.3 to 2.9), respectively. Primary MR was the most common aetiology (124/203, 61.1%). Almost half of cases were newly diagnosed by screening: MR 98/203 (48.3%), TR 69/155 (44.5%). Subjects diagnosed by screening were less symptomatic, more likely to have primary MR and had a lower incidence of aortic valve disease. Surgical intervention was undertaken in six subjects (2.4%) over a median follow-up of 64 months. Five-year survival was 79.8% in subjects with isolated MR, 84.8% in those with isolated TR, and 59.4% in those with combined MR and TR (p=0.0005).
Conclusions
Moderate or greater MR/TR is common, age-dependent and is underdiagnosed. Current rates of valve intervention are extremely low.

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

Heart: 03 Mar 2021; epub ahead of print
Cahill TJ, Prothero A, Wilson J, Kennedy A, ... Prendergast BD, Myerson SG
Heart: 03 Mar 2021; epub ahead of print | PMID: 33674352
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Abstract

B-type natriuretic peptide and cardiac remodelling after myocardial infarction: a randomised trial.

Hubers SA, Schirger JA, Sangaralingham SJ, Chen Y, ... Hodge D, Chen HH
Objective
B-type natriuretic peptide (BNP) has favourable effects on left ventricular remodelling, including antifibrotic and antiapoptotic properties. We tested the hypothesis that infusion of BNP after an acute myocardial infarction would reduce left ventricular systolic and diastolic volumes and improve left ventricular ejection fraction compared with placebo.
Methods
A total of 58 patients who underwent successful revascularisation for an acute ST elevation anterior myocardial infarction were randomised to receive 72-hour infusion of BNP at 0.006 µg/kg/min or placebo. Left ventricular end diastolic and systolic volumes and left ventricular ejection fraction were measured at baseline and at 30 days by multigated acquisition scan. Left ventricular infarction size was measured by cardiac MRI.
Results
BNP infusion led to significantly higher BNP levels and plasma cyclic guanosine monophosphate at 72 hours. No significant difference in change of left ventricular volumes or ejection fraction from baseline to 30 days was observed between groups. Although left ventricular infarction size measured by cardiac MRI was not significantly different between BNP infusion versus placebo (p=0.39), there was a trend towards reduced infarction size in patients with a baseline ejection fraction of <40% (p=0.14).
Conclusions
Infusion of BNP in patients with an anterior myocardial infarction did not affect parameters of left ventricular remodelling. Patients treated with BNP who had a baseline left ventricular ejection fraction of <40% had a trend towards reduced left ventricular infarction size compared with placebo. These results do not support the use of intravenous BNP in patients after recent myocardial infarction.
Trial registration number
NCT00573144.

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

Heart: 27 Feb 2021; 107:396-402
Hubers SA, Schirger JA, Sangaralingham SJ, Chen Y, ... Hodge D, Chen HH
Heart: 27 Feb 2021; 107:396-402 | PMID: 32747497
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Impact:
Abstract

Cost-effectiveness of cardiovascular imaging for stable coronary heart disease.

Walker S, Cox E, Rothwell B, Berry C, ... Greenwood JP, Sculpher M
Objective
To assess the cost-effectiveness of management strategies for patients presenting with chest pain and suspected coronary heart disease (CHD): (1) cardiovascular magnetic resonance (CMR); (2) myocardial perfusion scintigraphy (MPS); and (3) UK National Institute for Health and Care Excellence (NICE) guideline-guided care.
Methods
Using UK data for 1202 patients from the Clinical Evaluation of Magnetic Resonance Imaging in Coronary Heart Disease 2 trial, we conducted an economic evaluation to assess the cost-effectiveness of CMR, MPS and NICE guidelines. Health outcomes were expressed as quality-adjusted life-years (QALYs), and costs reflected UK pound sterling in 2016-2017. Cost-effectiveness results were presented as incremental cost-effectiveness ratios and incremental net health benefits overall and for low, medium and high pretest likelihood of CHD subgroups.
Results
CMR had the highest estimated QALY gain overall (2.21 (95% credible interval 2.15, 2.26) compared with 2.07 (1.92, 2.20) for NICE and 2.11 (2.01, 2.22) for MPS) and incurred comparable costs (overall £1625 (£1431, £1824) compared with £1753 (£1473, £2032) for NICE and £1768 (£1572, £1989) for MPS). Overall, CMR was the cost-effective strategy, being the dominant strategy (more effective, less costly) with incremental net health benefits per patient of 0.146 QALYs (-0.18, 0.406) compared with NICE guidelines at a cost-effectiveness threshold of £15 000 per QALY (93% probability of cost-effectiveness). Results were similar in the pretest likelihood subgroups.
Conclusions
CMR-guided care is cost-effective overall and across all pretest likelihood subgroups, compared with MPS and NICE guidelines.

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

Heart: 27 Feb 2021; 107:381-388
Walker S, Cox E, Rothwell B, Berry C, ... Greenwood JP, Sculpher M
Heart: 27 Feb 2021; 107:381-388 | PMID: 32817271
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Abstract

Parameters associated with ventricular arrhythmias in mitral valve prolapse with significant regurgitation.

van Wijngaarden AL, de Riva M, Hiemstra YL, van der Bijl P, ... Delgado V, Ajmone Marsan N
Objective
Mitral valve prolapse (MVP) has been associated with ventricular arrhythmias (VA), but little is known about VA in patients with significant primary mitral regurgitation (MR). Our aim was to describe the prevalence of symptomatic VA in patients with MVP (fibro-elastic deficiency or Barlow\'s disease) referred for mitral valve (MV) surgery because of moderate-to-severe MR, and to identify clinical, electrocardiographic, standard and advanced echocardiographic parameters associated with VA.
Methods
610 consecutive patients (64±12 years, 36% female) were included. Symptomatic VA was defined as symptomatic and frequent premature ventricular contractions (PVC, Lown grade ≥2), non-sustained or sustained ventricular tachycardia (VT) or ventricular fibrillation (VF) without ischaemic aetiology.
Results
A total of 67 (11%) patients showed symptomatic VA, of which 3 (4%) had VF, 3 (4%) sustained VT, 27 (40%) non-sustained VT and 34 (51%) frequent PVCs. Patients with VA were significantly younger, more often female and showed T-wave inversions; furthermore, they showed significant MV morphofunctional abnormalities, such as mitral annular disjunction (39% vs 20%, p<0.001), and dilatation (annular diameter 37±5 mm vs 33±6 mm, p<0.001), lower global longitudinal strain (GLS 20.9±3.1% vs 22.0±3.6%, p=0.032) and prolonged mechanical dispersion (45±12 ms vs 38±14 ms, p=0.003) as compared with patients without VA. Female sex, increased MV annular diameter, lower GLS and prolonged mechanical dispersion were identified as independent associates of symptomatic VA.
Conclusion
In patients with MVP with moderate-to-severe MR, symptomatic VA are relatively frequent and associated with significant MV annular abnormalities, subtle left ventricular function impairment and heterogeneous contraction. Assessment of these parameters might help decision-making over further diagnostic analyses and improve risk-stratification.

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

Heart: 27 Feb 2021; 107:411-418
van Wijngaarden AL, de Riva M, Hiemstra YL, van der Bijl P, ... Delgado V, Ajmone Marsan N
Heart: 27 Feb 2021; 107:411-418 | PMID: 33004425
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Impact:
Abstract

Determinants of clinical outcomes of surgery for isolated severe tricuspid regurgitation.

Park SJ, Oh JK, Kim SO, Lee SA, ... Kim DH, Kim JB
Objectives
Although the incidence of patients with isolated tricuspid regurgitation (TR) is increasing, data regarding the clinical outcomes of isolated TR surgery are limited. This study sought to investigate the prognostic implications according to procedural types, and to identify preoperative predictors of clinical outcomes after isolated TR surgery.
Methods
Among consecutive 2610 patients receiving tricuspid valve (TV) procedure, we analysed 238 patients (age, 59.6 years; 143 females) who underwent stand-alone TV surgery (repair, 132; replacement, 106) for severe TR. Primary outcome was the composite of all-cause mortality and heart transplantation. Clinical outcomes between the repair and the replacement groups were compared after adjusting with the inverse probability of treatment weighting (IPTW) method.
Results
During follow-up (median, 4.1 years), 53 patients died and 4 received heart transplantation. Multivariable analysis revealed that age (p=0.001), haemoglobin level (p=0.003), total bilirubin (p=0.040), TR jet area (p=0.005) and right atrial (RA) pressure (p=0.022) were independent predictors of the primary outcome. After IPTW adjustment, there were no significant intergroup differences in the risk of primary outcome (HR 1.01; 95% CI 0.55 to 1.87). In the subgroup analysis, tricuspid annular diameter was identified as a significant effect modifier (p=0.012) in the comparison between repair versus replacement, showing a trend favouring replacement in patients with annular diameter >44 mm.
Conclusions
The outcomes of stand-alone severe TR surgery were independently associated with the severity of TR and RA pressure. In selected patients with severe annular dilation >44 mm, replacement may become a feasible option.

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

Heart: 27 Feb 2021; 107:403-410
Park SJ, Oh JK, Kim SO, Lee SA, ... Kim DH, Kim JB
Heart: 27 Feb 2021; 107:403-410 | PMID: 33139325
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Impact:
Abstract

Long-term survival benefit of ramipril in patients with acute myocardial infarction complicated by heart failure.

Wu J, Hall AS, Gale CP, AIREX Study Investigators
Aims
ACE inhibition reduces mortality and morbidity in patients with heart failure after acute myocardial infarction (AMI). However, there are limited randomised data about the long-term survival benefits of ACE inhibition in this population.
Methods
In 1993, the Acute Infarction Ramipril Efficacy (AIRE) study randomly allocated patients with AMI and clinical heart failure to ramipril or placebo. The duration of masked trial therapy in the UK cohort (603 patients, mean age=64.7 years, 455 male patients) was 12.4 and 13.4 months for ramipril (n=302) and placebo (n=301), respectively. We estimated life expectancy and extensions of life (difference in median survival times) according to duration of follow-up (range 0-29.6 years).
Results
By 9 April 2019, death from all causes occurred in 266 (88.4%) patients in placebo arm and 275 (91.1%) patients in ramipril arm. The extension of life between ramipril and placebo groups was 14.5 months (95% CI 13.2 to 15.8). Ramipril increased life expectancy more for patients with than without diabetes (life expectancy difference 32.1 vs 5.0 months), previous AMI (20.1 vs 4.9 months), previous heart failure (19.5 vs 4.9 months), hypertension (16.6 vs 8.3 months), angina (16.2 vs 5.0 months) and age >65 years (11.3 vs 5.7 months). Given potential treatment switching, the true absolute treatment effect could be underestimated by 28%.
Conclusion
For patients with clinically defined heart failure following AMI, ramipril results in a sustained survival benefit, and is associated with an extension of life of up to 14.5 months for, on average, 13 months treatment duration.

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

Heart: 27 Feb 2021; 107:389-395
Wu J, Hall AS, Gale CP, AIREX Study Investigators
Heart: 27 Feb 2021; 107:389-395 | PMID: 33452123
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Impact:
Abstract

Sodium-glucose co-transporter 2 inhibitor therapy: mechanisms of action in heart failure.

Joshi SS, Singh T, Newby DE, Singh J
Patients with type 2 diabetes mellitus are at a higher risk of developing heart failure compared with the healthy population. In recent landmark clinical trials, sodium-glucose co-transporter 2 (SGLT2) inhibitor therapies improve blood glucose control and also reduce cardiovascular events and heart failure hospitalisations in patients with type 2 diabetes. Intriguingly, such clinical benefits have also been seen in patients with heart failure in the absence of type 2 diabetes although the underlying mechanisms are not clearly understood. Potential pathways include improved glycaemic control, diuresis, weight reduction and reduction in blood pressure, but none fully explain the observed improvements in clinical outcomes. More recently, novel mechanisms have been proposed to explain these benefits that include improved cardiomyocyte calcium handling, enhanced myocardial energetics, induced autophagy and reduced epicardial fat. We provide an up-to-date review of cardiac-specific SGLT2 inhibitor-mediated mechanisms and highlight studies currently underway investigating some of the proposed mechanisms of action in cardiovascular health and disease.

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

Heart: 25 Feb 2021; epub ahead of print
Joshi SS, Singh T, Newby DE, Singh J
Heart: 25 Feb 2021; epub ahead of print | PMID: 33637556
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Impact:
Abstract

National Institute for Health and Care Excellence clinical guidelines development principles and processes.

Garbi M
Clinical guidelines are developed by professional societies and also, in England, by an independent non-departmental public body, the National Institute for Health and Care Excellence (NICE). Similarities and differences between these guidelines should be viewed in the context of different objectives, responsibilities and roles of guideline developers. This review describes the NICE clinical guidelines development principles and processes with the aim to provide the reader an informed perspective on the recommendations made. NICE clinical guidelines are developed by an appointed independent advisory committee comprising healthcare professionals as well as lay members, supported by a professional team comprising project managers, information specialists, systematic reviewers and health economists. Furthermore, registered stakeholders comprising organisations that have an interest in the guideline topic, or represent people whose practice or care may be directly affected by the guideline, are consulted on the draft scope and draft guidelines. NICE selects a limited number of high impact questions to be answered by the review of evidence, rather than cover a certain topic exhaustively as the clinical guidelines developed by professional societies may do. NICE clinical guidelines recommendations reflect both the clinical effectiveness and the cost-effectiveness of interventions.

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

Heart: 22 Feb 2021; epub ahead of print
Garbi M
Heart: 22 Feb 2021; epub ahead of print | PMID: 33622678
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Impact:
Abstract

Postmenopausal hormone therapy for cardiovascular health: the evolving data.

Gersh FL, O\'Keefe JH, Lavie CJ
Postmenopausal (PM) hormone therapy (HT) was extremely popular for years as a treatment for many conditions, including cardiovascular (CV) disease (CVD) prevention. The adverse results from the Women\'s Health Initiative (WHI) ended the widespread prescriptive use of HT for nearly 20 years. The WHI findings have been broadly and unfairly applied to all hormone formulations, including modern treatments using human-identical hormones. Although CV health is indisputably linked to oestrogen status, HT involving any combination of hormones currently is not recommended for primary or secondary prevention of CVD. In the wake of more positive results from recent studies and re-evaluation of the WHI, HT has re-emerged as an issue for specialists in CVD to discuss with their patients. Rigorous scientific analysis is needed to explain the paradox of cardioprotection conferred by endogenous ovarian hormones with apparent cardiotoxicity inflicted by HT. This review will cover the origins of HT, hormone terminology and function, and key studies that contribute to our current understanding. Based on evolving evidence, if HT is to be used, we propose it be initiated immediately after cessation of ovarian hormone production and dosed as transdermal oestradiol combined with cyclic dosing of human-identical progesterone (P4).

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

Heart: 21 Feb 2021; epub ahead of print
Gersh FL, O'Keefe JH, Lavie CJ
Heart: 21 Feb 2021; epub ahead of print | PMID: 33619206
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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: 15 Feb 2021; epub ahead of print
Pugh D, Grayson P, Basu N, Dhaun N
Heart: 15 Feb 2021; epub ahead of print | PMID: 33593995
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Impact:
Abstract

Comparative effectiveness of oral anticoagulants in everyday practice.

Camm AJ, Fox KAA, Virdone S, Bassand JP, ... Kakkar AK, GARFIELD-AF investigators
Objectives
This study evaluated the comparative effectiveness of vitamin K antagonists (VKAs), direct thrombin inhibitors (DTIs) and factor Xa inhibitors (FXaI) in patients with atrial fibrillation (AF) at risk of stroke in everyday practice.
Methods
Data from patients with AF and Congestive heart failure, Hypertension, Age 75 years, Diabetes mellitus, prior Stroke, TIA, or thromboembolism, Vascular disease, Age 65-74 years, Sex category (CHA2DS2-VASc) score ≥2 (excluding gender) in the Global Anticoagulant Registry in the FIELD-Atrial Fibrillation registry were analysed using an improved method of propensity weighting, overlap weights and Cox proportional hazards models.
Results
All-cause mortality, non-haemorrhagic stroke/systemic embolism (SE) and major bleeding over 2 years were compared in 25 551 patients, 7162 (28.0%) not treated with oral anticoagulant (OAC) and 18 389 (72.0%) treated with OAC (FXaI (41.8%), DTI (11.4%) and VKA (46.8%)). OAC treatment compared with no OAC treatment was associated with decreased risk of all-cause mortality (HR 0.82 (95% CI 0.74 to 0.91)) and non-haemorrhagic stroke/SE (HR 0.71 (95% CI 0.57 to 0.88)) but increased risk of major bleeding (HR 1.46 (95% CI 1.15 to 1.86)). Non-vitamin K antagonist oral anticoagulant (NOAC) use compared with no OAC treatment was associated with lower risks of all-cause mortality and non-haemorrhagic stroke/SE (HR 0.67 (95% CI 0.59 to 0.77)) and 0.65 (95% CI 0.50 to 0.86)) respectively, with no increase in major bleeding (HR 1.10 (95% CI 0.82 to 1.47)). NOAC use compared with VKA use was associated with lower risk of all-cause mortality and major bleeding (rates/100 patient-years 3.6 (95% CI 3.3 to 3.9) vs 4.8 (95% CI 4.5 to 5.2) and 1.0 (95% CI 0.9 to 1.1) vs 1.4 (95% CI 1.2 to 1.6); HR 0.79 (95% CI 0.70 to 0.89) and 0.77 (95% CI 0.61 to 0.98) respectively), with similar risk of non-haemorrhagic stroke/SE (rates/100 patient-years 0.8 (95% CI 0.7 to 0.9) versus 1.0 (95% CI 0.8 to 1.1); HR 0.96 (95% CI 0.73 to 1.25).
Conclusion
Important benefits in terms of mortality and major bleeding were observed with NOAC versus VKA with no difference among NOAC subtypes.
Trial registration number
NCT01090362.

© 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: 15 Feb 2021; epub ahead of print
Camm AJ, Fox KAA, Virdone S, Bassand JP, ... Kakkar AK, GARFIELD-AF investigators
Heart: 15 Feb 2021; epub ahead of print | PMID: 33593994
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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: 10 Feb 2021; epub ahead of print
Shahandeh N, Chowdhary H, Middlekauff HR
Heart: 10 Feb 2021; epub ahead of print | PMID: 33574049
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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: 09 Feb 2021; epub ahead of print
Singh T, Chapman AR, Dweck MR, Mills NL, Newby DE
Heart: 09 Feb 2021; epub ahead of print | PMID: 33568434
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Abstract

Chronic kidney disease detection, staging and treatment in cardiovascular disease prevention.

Lamprea-Montealegre JA, Shlipak MG, Estrella MM
Globally, nearly 10% of the population has chronic kidney disease (CKD), defined as a glomerular filtration rate less than 60 mL/min/1.73 m2 and/or a urinary albumin to creatinine ratio greater than 30 mg/g (3 mg/mmol). Persons with CKD have a substantially high risk of cardiovascular disease. Indeed, most persons with CKD are far more likely to develop a cardiovascular event than to progress to end-stage kidney disease. Although early detection and staging of CKD could help prevent its cardiovascular consequences, current rates of testing for CKD are very low, even among high-risk populations such as persons with diabetes, hypertension and cardiovascular disease. In this review, we first describe the need to test for both estimated glomerular filtration rate and albuminuria among persons at high risk of CKD in order to properly stage CKD and enhance cardiovascular risk stratification. We then discuss how detection and staging for CKD could help prioritise patients at high risk of atherosclerotic cardiovascular disease and heart failure who could derive the largest benefit from cardiovascular preventive interventions. In addition, we discuss the central role of CKD detection and staging in the initiation of cardiorenal preventive therapies, such as the sodium-glucose cotransporter 2 inhibitors, which have shown overwhelming evidence of cardiorenal protection. We conclude by discussing strategies to overcome historical barriers to CKD detection and treatment.

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

Heart: 09 Feb 2021; epub ahead of print
Lamprea-Montealegre JA, Shlipak MG, Estrella MM
Heart: 09 Feb 2021; epub ahead of print | PMID: 33568433
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Abstract

Influence of sex and phenotype on cardiac outcomes in patients with Fabry disease.

El Sayed M, Hirsch A, Boekholdt M, van Dussen L, ... Hollak C, Langeveld M
Objective
This study describes the influence of sex and disease phenotype on the occurrence of cardiac events in Fabry disease (FD).
Methods
Cardiac events from birth to last visit (median age 50 years) were recorded for 213 patients with FD. Patients were categorised as follows : men with classical FD (n=57), men with non-classical FD (n=26), women with classical FD (n=98) and women with non-classical FD (n=32), based on the presence of classical FD symptoms, family history (men and women), biomarkers and residual enzyme activity (men). Event rates per 1000 patient-years after the age of 15 years and median event-free survival (EVS) age were presented. Influence of disease phenotype, sex and their interaction was studied using Firth\'s penalised Cox regression.
Results
The event rates of major cardiovascular events (combined endpoint cardiovascular death (CVD), heart failure (HF) hospitalisation, sustained ventricular arrhythmias (SVAs) and myocardial infarction) were 11.0 (95% CI 6.6 to 17.3) in men with classical FD (EVS 55 years), 4.4 (95% CI 2.5 to 7.1) in women with classical FD (EVS 70 years) and 5.9 (95% CI 2.6 to 11.6) in men with non-classical FD (EVS 70 years). None of these events occurred in women with non-classical FD. Sex and phenotype significantly influenced the risk of major adverse cardiovascular event. CVD was the leading cause of death (75%) to which HF contributed most (42%). The overall rate of SVA was low (14 events in nine patients (4%)).
Conclusions
Sex and phenotype greatly influence the risk and age of onset of cardiac events in FD. This indicates the need for patient group-specific follow-up and treatment.

© 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 Feb 2021; epub ahead of print
El Sayed M, Hirsch A, Boekholdt M, van Dussen L, ... Hollak C, Langeveld M
Heart: 09 Feb 2021; epub ahead of print | PMID: 33568430
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Abstract

Standard ECG for differential diagnosis between Anderson-Fabry disease and hypertrophic cardiomyopathy.

Vitale G, Ditaranto R, Graziani F, Tanini I, ... Rapezzi C, Biagini E
Objectives
To evaluate the role of the ECG in the differential diagnosis between Anderson-Fabry disease (AFD) and hypertrophic cardiomyopathy (HCM).
Methods
In this multicentre retrospective study, 111 AFD patients with left ventricular hypertrophy were compared with 111 patients with HCM, matched for sex, age and maximal wall thickness by propensity score. Independent ECG predictors of AFD were identified by multivariate analysis, and a multiparametric ECG score-based algorithm for differential diagnosis was developed.
Results
Short PR interval, prolonged QRS duration, right bundle branch block (RBBB), R in augmented vector left (aVL) ≥1.1 mV and inferior ST depression independently predicted AFD diagnosis. A point-by-point ECG score was then derived with the following diagnostic performances: c-statistic 0.80 (95% CI 0.74 to 0.86) for discrimination, the Hosmel-Lemeshow χ2 6.14 (p=0.189) for calibration, sensitivity 69%, specificity 84%, positive predictive value 82% and negative predictive value 72%. After bootstrap resampling, the mean optimism was 0.025, and the internal validated c-statistic for the score was 0.78.
Conclusions
Standard ECG can help to differentiate AFD from HCM while investigating unexplained left ventricular hypertrophy. Short PR interval, prolonged QRS duration, RBBB, R in aVL ≥1.1 mV and inferior ST depression independently predicted AFD. Their systematic evaluation and the integration in a multiparametric ECG score can support AFD diagnosis.

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

Heart: 08 Feb 2021; epub ahead of print
Vitale G, Ditaranto R, Graziani F, Tanini I, ... Rapezzi C, Biagini E
Heart: 08 Feb 2021; epub ahead of print | PMID: 33563631
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Abstract

Patient values and preferences on valve replacement for aortic stenosis: a systematic review.

Heen AF, Lytvyn L, Shapiro M, Guyatt GH, ... Vandvik PO, Agoritsas T
The review aims to summarise evidence addressing patients\' values, preferences and practical issues on deciding between transcatheter aortic valve insertion (TAVI) and surgical aortic valve replacement (SAVR) for aortic stenosis. We searched databases and grey literature until June 2020. We included studies of adults with aortic stenosis eliciting values and preferences about treatment, excluding medical management or palliative care. Qualitative findings were synthesised using thematic analysis, and quantitative findings were narratively described. Evidence certainty was assessed using CERQual (Confidence in the Evidence from Reviews of Qualitative Research) and GRADE (Grading of Recommendations Assessment, Development and Evaluation). We included eight studies. Findings ranged from low to very low certainty. Most studies only addressed TAVI. Studies addressing both TAVI and SAVR reported on factors affecting patients\' decision-making along with treatment effectiveness, instead of trade-offs between procedures. Willingness to accept risk varied considerably. To improve their health status, participants were willing to accept higher mortality risk than current evidence suggests for either procedure. No study explicitly addressed valve reintervention, and one study reported variability in willingness to accept shorter duration of known effectiveness of TAVI compared with SAVR. The most common themes were desire for symptom relief and improved function. Participants preferred minimally invasive procedures with shorter hospital stay and recovery. The current body of evidence on patients\' values, preferences and practical issues related to aortic stenosis management is of suboptimal rigour and reports widely disparate results regarding patients\' perceptions. These findings emphasise the need for higher quality studies to inform clinical practice guidelines and the central importance of shared decision-making to individualise care fitted to each patient.

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

Heart: 08 Feb 2021; epub ahead of print
Heen AF, Lytvyn L, Shapiro M, Guyatt GH, ... Vandvik PO, Agoritsas T
Heart: 08 Feb 2021; epub ahead of print | PMID: 33563630
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Abstract

Aortic arch stenting: current strategies, new technologies and future directions.

Dhanekula AS, Sweet MP, Desai N, Burke CR
Operating on the aortic arch is a formidable challenge. Open operations remain the gold standard, but despite improvement in technique and outcomes, they are still associated with significant morbidity and mortality. The last 20 years have seen a remarkable reduction in the operative morbidity associated with treatment of the descending thoracic aorta using thoracic endovascular aneurysm repair (TEVAR). To improve outcomes following arch repair, new TEVAR devices, including both single-branched and multibranched designs, have come to clinical trial. This review discusses the modern state of open and hybrid repairs while introducing the reader to technology for endovascular therapy of the aortic arch. We describe important anatomical and operative considerations for the devices. Given these nuances, we believe the future of the aortic arch to be patient-individualised hybrid repairs, involving both open and endovascular options with a multidisciplinary \'thoracic aorta team\' at the helm.

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

Heart: 03 Feb 2021; epub ahead of print
Dhanekula AS, Sweet MP, Desai N, Burke CR
Heart: 03 Feb 2021; epub ahead of print | PMID: 33541853
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Abstract

Global longitudinal strain predicts cardiovascular events after coronary artery bypass grafting.

Olsen FJ, Lindberg S, Pedersen S, Iversen A, ... Møgelvang R, Biering-Sørensen T
Objective
To determine the prognostic value of global longitudinal strain (GLS) after coronary artery bypass grafting (CABG).
Methods
We performed a retrospective cohort study on patients undergoing CABG between 2006 and 2011 who had an echocardiogram available for strain analysis. The patients were followed up through nationwide registries for development of all-cause mortality, cardiovascular death (CVD) and major adverse cardiovascular events (MACEs) defined as heart failure hospitalisation and/or CVD. Multivariable Cox regression was applied to adjust for the European System for Cardiac Operative Risk Evaluation II (EuroSCORE-II). Additive value was assessed by Net Reclassification Index (NRI) improvement.
Results
Of the 709 patients included, 80 died during a median follow-up of 3.8 years. Of these, 45 had CVD, and 72 patients experienced MACE. Mean age was 68 years and 85% were men. Left ventricular ejection fraction (LVEF) was 50% and GLS was -13%.GLS was an independent predictor when adjusted for the EuroSCORE-II (all-cause mortality: HR=1.07 (1.01-1.13), p=0.018; CVD: HR=1.11 (1.03-1.20), p=0.007; MACE: HR=1.12 (1.06-1.19), p<0.001, per 1% absolute decrease). GLS significantly improved the NRI score by 0.30 when added to the EuroSCORE-II for predicting MACE, but not significantly for the other endpoints.LVEF modified the association between GLS and outcomes (p for interaction<0.05 for CVD and MACE). GLS remained an independent predictor of outcomes in patients with preserved LVEF (LVEF≥50%) and improved the NRI score when added to the EuroSCORE-II for predicting CVD and MACE, but not all-cause mortality in these patients.
Conclusion
GLS is an independent predictor of long-term outcomes after CABG. The predictive value appears strongest among patients with preserved LVEF.

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

Heart: 31 Jan 2021; epub ahead of print
Olsen FJ, Lindberg S, Pedersen S, Iversen A, ... Møgelvang R, Biering-Sørensen T
Heart: 31 Jan 2021; epub ahead of print | PMID: 33526506
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Abstract

Lower socioeconomic status predicts higher mortality and morbidity in patients with heart failure.

Schrage B, Lund LH, Benson L, Stolfo D, ... Ferreira JP, Savarese G
Objective
It is not fully understood whether and how socioeconomic status (SES) has a prognostic impact in patients with heart failure (HF). We assessed SES and its association with patient characteristics and outcomes in a contemporary and well-characterised HF cohort.
Methods
Socioeconomic risk factors (SERF) were defined in the Swedish HF Registry based on income (low vs high according to the annual median value), education level (no degree/compulsory school vs university/secondary school) and living arrangement (living alone vs cohabitating).
Results
Of 44 631 patients, 21% had no, 33% one, 30% two and 16% three SERF. Patient characteristics strongly and independently associated with lower SES were female sex and no specialist referral. Additional independent associations were older age, more severe HF, heavier comorbidity burden, use of diuretics and less use of HF devices. Lower SES was associated with higher risk of HF hospitalisation/mortality, and overall cardiovascular and non-cardiovascular events. These associations persisted after extensive adjustment for patient characteristics, treatments and care. The magnitude of the association increased linearly with the increasing number of coexistent SERF: HR (95% CI) 1.09 (1.05 to 1.13) for one, 1.16 (1.12 to 1.20) for two and 1.22 (1.18 to 1.28) for three SERF (p<0.01).
Conclusions
In a contemporary and well-characterised HF cohort and after comprehensive adjustment for confounders, lower SES was linked with multiple factors such as less use of HF devices and age, but most strongly with female sex and lack of specialist referral; and associated with greater risk of morbidity/mortality.

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

Heart: 30 Jan 2021; 107:229-236
Schrage B, Lund LH, Benson L, Stolfo D, ... Ferreira JP, Savarese G
Heart: 30 Jan 2021; 107:229-236 | PMID: 32769169
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Abstract

D-dimer and the incidence of heart failure and mortality after acute myocardial infarction.

Zhang X, Wang S, Liu J, Wang Y, ... Fang S, Yu B
Objective
D-dimer might serve as a marker of thrombogenesis and a hypercoagulable state following plaque rupture. Few studies explore the association between baseline D-dimer levels and the incidence of heart failure (HF), all-cause mortality in an acute myocardial infarction (AMI) population. We aimed to explore this association.
Methods
We enrolled 4504 consecutive patients with AMI with complete data in a prospective cohort study and explored the association of plasma D-dimer levels on admission and the incidence of HF, all-cause mortality.
Results
Over a median follow-up of 1 year, 1112 (24.7%) patients developed in-hospital HF, 542 (16.7%) patients developed HF after hospitalisation and 233 (7.1%) patients died. After full adjustments for other relevant clinical covariates, patients with D-dimer values in quartile 3 (Q3) had 1.51 times (95% CI 1.12 to 2.04) and in Q4 had 1.49 times (95% CI 1.09 to 2.04) as high as the risk of HF after hospitalisation compared with patients in Q1. Patients with D-dimer values in Q4 had more than a twofold (HR 2.34; 95% CI 1.33 to 4.13) increased risk of death compared with patients in Q1 (p<0.001). But there was no association between D-dimer levels and in-hospital HF in the adjusted models.
Conclusions
D-dimer was found to be associated with the incidence of HF after hospitalisation and all-cause mortality in patients with AMI.

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

Heart: 30 Jan 2021; 107:237-244
Zhang X, Wang S, Liu J, Wang Y, ... Fang S, Yu B
Heart: 30 Jan 2021; 107:237-244 | PMID: 32788198
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Impact:
Abstract

Prevalence and incidence rates of atrial fibrillation in Norway 2004-2014.

Kjerpeseth LJ, Igland J, Selmer R, Ellekjær H, ... Tell GS, Ariansen I
Objective
To study time trends in incidence of atrial fibrillation (AF) in the entire Norwegian population from 2004 to 2014, by age and sex, and to estimate the prevalence of AF at the end of the study period.
Methods
A national cohort of patients with AF (≥18 years) was identified from inpatient admissions with AF and deaths with AF as underlying cause (1994-2014), and AF outpatient visits (2008-2014) in the Cardiovascular Disease in Norway (CVDNOR) project. AF admissions or out-of-hospital death from AF, with no AF admission the previous 10 years defined incident AF. Age-standardised incidence rates (IR) and incidence rate ratios (IRR) were calculated. All AF cases identified through inpatient admissions and outpatient visits and alive as of 31 December 2014 defined AF prevalence.
Results
We identified 175 979 incident AF cases (30% primary diagnosis, 69% secondary diagnosis, 0.6% out-of-hospital deaths). AF IRs (95% confidence intervals) per 100 000 person years were stable from 2004 (433 (426-440)) to 2014 (440 (433-447)). IRs were stable or declining across strata of sex and age with the exception of an average yearly increase of 2.4% in 18-44 year-olds: IRR 1.024 (1.014-1.034). In 2014, the prevalence of AF in the adult population was 3.4%.
Conclusions
We found overall stable IRs of AF for the adult Norwegian population from 2004 to 2014. The prevalence of AF was 3.4% at the end of 2014, which is higher than reported in previous studies. Signs of an increasing incidence of early-onset AF (<45 years) are worrying and need further investigation.

© 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 Jan 2021; 107:201-207
Kjerpeseth LJ, Igland J, Selmer R, Ellekjær H, ... Tell GS, Ariansen I
Heart: 30 Jan 2021; 107:201-207 | PMID: 32820014
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Abstract

Residual risks of ischaemic stroke and systemic embolism among atrial fibrillation patients with anticoagulation: large-scale real-world data (F-CREATE project).

Maeda T, Nishi T, Funakoshi S, Tada K, ... Yoshimura C, Arima H
Objective
Among patients with atrial fibrillation, the risks of ischaemic stroke and systemic embolism (IS/SE) are high even with effective anticoagulation. Using large-scale, real-world data from Japan, this study aims to clarify residual risks of IS/SE attributable to modifiable risk factors among patients with atrial fibrillation who are taking oral anticoagulants.
Methods
The study design we employed was a retrospective cohort. Health check-ups and insurance claims data of Japanese health insurance companies were accumulated from January 2005 to June 2017. We identified 11 848 participants with atrial fibrillation who were on oral anticoagulants during the study period. We set the modifiable risk factors as hypertension, diabetes and dyslipidaemia. A Cox proportional hazards model was used to obtain the effects of the risk factors for IS/SE.
Results
During an average of 3 years\' follow-up, 200 cases of IS/SE occurred (incidence rate 0.57 per 100 person-years). In multivariable analyses, older age (65-74 vs <65 years; adjusted HR 2.02 (95% CI 1.49 to 2.73)), hypertension (adjusted HR 1.41 (1.04 to 1.92)) and dyslipidaemia (adjusted HR 1.46 (1.07 to 1.98)) were significantly associated with increased risk of IS/SE. Percentage of IS/SE risk attributable to modifiable risk factors (hypertension, diabetes and dyslipidaemia) was 30.0% (16.1% to 41.6%).
Conclusion
Among patients with atrial fibrillation on anticoagulant therapy, approximately one-third of the residual risks were estimated to be attributable to modifiable risk factors such as hypertension, diabetes and dyslipidaemia.

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

Heart: 30 Jan 2021; 107:217-222
Maeda T, Nishi T, Funakoshi S, Tada K, ... Yoshimura C, Arima H
Heart: 30 Jan 2021; 107:217-222 | PMID: 32817313
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Impact:
Abstract

Income level and outcomes in patients with heart failure with universal health coverage.

Hung CL, Chao TF, Su CH, Liao JN, ... Yeh HI, Chiang CE
Objective
We aimed to investigate the influence of income level on guideline-directed medical therapy (GDMT) prescription rates and prognosis of patients with heart failure (HF) following implementation of a nationwide health insurance programme.
Methods
A total of 633 098 hospitalised patients with HF from 1996 to 2013 were identified from Taiwan National Health Insurance Research Database. Participants were classified into low-income, median-income and high-income groups. GDMT utilisation, in-hospital mortality and postdischarge HF readmission, and mortality rates were compared.
Results
The low-income group had a higher comorbidity burden and was less likely to receive GDMT than the other two groups. The in-hospital mortality rate in the low-income group (5.07%) was higher than in the median-income (2.47%) and high-income (2.51%) groups. Compared with the high-income group, the low-income group had a significantly higher risk of postdischarge HF readmission (adjusted HR (aHR): 1.29, 95% CI 1.27 to 1.31), all-cause mortality (aHR: 1.98, 95% CI 1.95 to 2.02) and composite HF readmission/all-cause mortality (aHR: 1.54, 95% CI 1.52 to 1.56). These results were generally consistent among the population after propensity matching (low vs high: HR=2.08 for mortality and 1.36 for HF readmission; median vs high: HR=1.23 for mortality and 1.12 for HF readmission; all p<0.001) and after inverse probability of treatment weighting (low-income vs high-income group: HR: 2.19 for mortality and 1.16 for HF readmission; median-income vs high-income group: HR: 1.53 for mortality and 1.09 for HF readmission; all p<0.001). Lower utilisation of GDMT and poorer prognosis in lower-income hospitalised patients with HF appeared to mitigate over time.
Conclusions
Low-income patients with HF had nearly a twofold increase in the risk of in-hospital mortality and postdischarge events compared with the high-income group, partly due to lower GDMT utilisation. The differences between postdischarge HF outcomes among various income groups appeared to mitigate over time following the implementation of nationwide universal health coverage.

© 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 Jan 2021; 107:208-216
Hung CL, Chao TF, Su CH, Liao JN, ... Yeh HI, Chiang CE
Heart: 30 Jan 2021; 107:208-216 | PMID: 33082175
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Impact:
Abstract

D-dimer blood concentrations to exclude left atrial thrombus in patients with atrial fibrillation.

Almorad A, Ohanyan A, Pintea Bentea G, Wielandts JY, ... Knecht S, Castro Rodriguez J
Objective
Left atrial (LA) thrombus is routinely excluded by transoesophageal echocardiography (TOE) before cardioversion for non-valvular atrial fibrillation (AF). In the D-dimer blood concentrations to exclude LA thrombus in patients with AF study, two D-dimer cut-offs were compared to exclude LA thrombus prior to cardioversion. One was fixed to 500 ng/mL (DD500), based on clinical practice where such values are commonly accepted to exclude a thrombus. The other cut-off was adjusted to 10 times the patient\'s age (DDAge), based on the cut-off used to exclude pulmonary embolism.
Methods
142 consecutive patients with non-valvular AF aged 69.7±11.4 years (52% with paroxysmal AF) referred for precardioversion TOE to exclude LA thrombus were prospectively enrolled. D-dimers were measured at the time of TOE by an ELISA test.
Results
LA thrombus was excluded with TOE in 129 (91%) and confirmed in 13 (9%) patients. D-dimers were significantly lower in patients without LA thrombus (729±611 vs 2376±1081 ng/L; p<0.05). DDAge indicated absence of LA thrombus with higher specificity than DD500 (66.4% vs 50.4%; p<0.05). Both cut-offs were able to identify all 13 patients with LA thrombus (false negative 0%). Patients with D-dimers <DDAge and without LA thrombus (true negative) represented 60.6% of the population and could have safely avoided TOE (flow chart).
Conclusions
This study demonstrates the efficacy of D-dimer cut-offs to exclude LA thrombus in patients with AF. Age adjustment greatly increases the proportion of patients in whom LA thrombus can be safely excluded and consequently avoid precardioversion TOE.

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

Heart: 30 Jan 2021; 107:195-200
Almorad A, Ohanyan A, Pintea Bentea G, Wielandts JY, ... Knecht S, Castro Rodriguez J
Heart: 30 Jan 2021; 107:195-200 | PMID: 33087410
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Impact:
Abstract

Obstructive sleep apnoea, intermittent hypoxia and heart failure with a preserved ejection fraction.

Sanderson JE, Fang F, Lu M, Ma CY, Wei YX
Obstructive sleep apnoea (OSA) is recognised to be a potent risk factor for hypertension, coronary heart disease, strokes and heart failure with a reduced ejection fraction. However, the association between OSA and heart failure with a preserved ejection fraction (HFpEF) is less well recognised. Both conditions are very common globally.It appears that there are many similarities between the pathological effects of OSA and other known aetiologies of HFpEF and its postulated pathophysiology. Intermittent hypoxia induced by OSA leads to widespread stimulation of the sympathetic nervous system, renin-angiotensin-aldosterone system and more importantly a systemic inflammatory state associated with oxidative stress. This is similar to the consequences of hypertension, diabetes, obesity and ageing that are the common precursors to HFpEF. The final common pathway is probably via the development of myocardial fibrosis and structural changes in collagen and myocardial titin that cause myocardial stiffening. Thus, considering the pathophysiology of OSA and HFpEF, OSA is likely to be a significant risk factor for HFpEF and further trials of preventive treatment should be considered.

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

Heart: 30 Jan 2021; 107:190-194
Sanderson JE, Fang F, Lu M, Ma CY, Wei YX
Heart: 30 Jan 2021; 107:190-194 | PMID: 33158933
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Impact:
Abstract

Cardiovascular genetics: the role of genetic testing in diagnosis and management of patients with hypertrophic cardiomyopathy.

Ahluwalia M, Ho CY
Genetic testing in hypertrophic cardiomyopathy (HCM) is a valuable tool to manage patients and their families. Genetic testing can help inform diagnosis and differentiate HCM from other disorders that also result in increased left ventricular wall thickness, thereby directly impacting treatment. Moreover, genetic testing can definitively identify at-risk relatives and focus family management. Pathogenic variants in sarcomere and sarcomere-related genes have been implicated in causing HCM, and targeted gene panel testing is recommended for patients once a clinical diagnosis has been established. If a pathogenic or likely pathogenic variant is identified in a patient with HCM, predictive genetic testing is recommended for their at-risk relatives to determine who is at risk and to guide longitudinal screening and risk stratification. However, there are important challenges and considerations to implementing genetic testing in clinical practice. Genetic testing results can have psychological and other implications for patients and their families, emphasising the importance of genetic counselling before and after genetic testing. Determining the clinical relevance of genetic testing results is also complex and requires expertise in understanding of human genetic variation and clinical manifestations of the disease. In this review, we discuss the genetics of HCM and how to integrate genetic testing in clinical practice.

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

Heart: 30 Jan 2021; 107:183-189
Ahluwalia M, Ho CY
Heart: 30 Jan 2021; 107:183-189 | PMID: 33172912
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Impact:
Abstract

Predictors of low exercise cardiac output in patients with severe pulmonic regurgitation.

Karsenty C, Khraiche D, Jais JP, Raimondi F, ... Iserin L, Legendre A
Background:
and objectives
Chronic pulmonic regurgitation (PR) following repair of congenital heart disease (CHD) impairs right ventricular function that impacts peak exercise cardiac index (pCI). We aimed to estimate in a non-invasive way pCI and peak oxygen consumption (pVO2) and to evaluate predictors of low pCI in patients with significant residual pulmonic regurgitation after CHD repair.
Method
We included 82 patients (median age 19 years (range 10-54 years)) with residual pulmonic regurgitation fraction >40%. All underwent cardiac MRI and cardiopulmonary testing with measurement of pCI by thoracic impedancemetry. Low pCI was defined <7 L/min/m2.
Results
Low pCI was found in 18/82 patients. Peak indexed stroke volume (pSVi) tended to compensate chronotropic insufficiency only in patients with normal pCI (r=-0.31, p=0.01). Below 20 years of age, only 5/45 patients had low pCI but near-normal (≥6.5 L/min/m2). pVO2 (mL/kg/min) was correlated with pCI (r=0.58, p=0.0002) only in patients aged >20 years. Left ventricular stroke volume in MRI correlated with pSVi only in the group of patients with low pCI (r=0.54, p=0.02). No MRI measurements predicted low pCI. In multivariable analysis, only age predicted a low pCI (OR=1.082, 95% CI 1.035 to 1.131, p=0.001) with continuous increase of risk with age.
Conclusions
In patients with severe PR, pVO2 is a partial reflection of pCI. Risk of low pCI increases with age. No resting MRI measurement predicts low haemodynamic response to exercise. Probably more suitable to detect ventricular dysfunction, pCI measurement could be an additional parameter to take into account when considering pulmonic valve replacement.

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

Heart: 30 Jan 2021; 107:223-228
Karsenty C, Khraiche D, Jais JP, Raimondi F, ... Iserin L, Legendre A
Heart: 30 Jan 2021; 107:223-228 | PMID: 33199362
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Abstract

Contrast-enhanced computed tomography assessment of aortic stenosis.

Cartlidge TR, Bing R, Kwiecinski J, Guzzetti E, ... Clavel MA, Dweck MR
Objectives
Non-contrast CT aortic valve calcium scoring ignores the contribution of valvular fibrosis in aortic stenosis. We assessed aortic valve calcific and non-calcific disease using contrast-enhanced CT.
Methods
This was a post hoc analysis of 164 patients (median age 71 (IQR 66-77) years, 78% male) with aortic stenosis (41 mild, 89 moderate, 34 severe; 7% bicuspid) who underwent echocardiography and contrast-enhanced CT as part of imaging studies. Calcific and non-calcific (fibrosis) valve tissue volumes were quantified and indexed to annulus area, using Hounsfield unit thresholds calibrated against blood pool radiodensity. The fibrocalcific ratio assessed the relative contributions of valve fibrosis and calcification. The fibrocalcific volume (sum of indexed non-calcific and calcific volumes) was compared with aortic valve peak velocity and, in a subgroup, histology and valve weight.
Results
Contrast-enhanced CT calcium volumes correlated with CT calcium score (r=0.80, p<0.001) and peak aortic jet velocity (r=0.55, p<0.001). The fibrocalcific ratio decreased with increasing aortic stenosis severity (mild: 1.29 (0.98-2.38), moderate: 0.87 (1.48-1.72), severe: 0.47 (0.33-0.78), p<0.001) while the fibrocalcific volume increased (mild: 109 (75-150), moderate: 191 (117-253), severe: 274 (213-344) mm3/cm2). Fibrocalcific volume correlated with ex vivo valve weight (r=0.72, p<0.001). Compared with the Agatston score, fibrocalcific volume demonstrated a better correlation with peak aortic jet velocity (r=0.59 and r=0.67, respectively), particularly in females (r=0.38 and r=0.72, respectively).
Conclusions
Contrast-enhanced CT assessment of aortic valve calcific and non-calcific volumes correlates with aortic stenosis severity and may be preferable to non-contrast CT when fibrosis is a significant contributor to valve obstruction.

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

Heart: 28 Jan 2021; epub ahead of print
Cartlidge TR, Bing R, Kwiecinski J, Guzzetti E, ... Clavel MA, Dweck MR
Heart: 28 Jan 2021; epub ahead of print | PMID: 33514522
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Abstract

Atrial fibrillation prevalence, awareness and management in a nationwide survey of adults in China.

Du X, Guo L, Xia S, Du J, ... Dong J, Ma C
Objective
To determine AF prevalence and gaps in atrial fibrillation (AF) awareness and management in China.
Methods
We conducted a community-based survey of 47 841 adults (age ≥45 years) in seven geographic regions of China between 2014 and 2016. Participants underwent a structured questionnaire, a standard 12-lead ECG, physical examination and blood sampling. AF prevalence, defined by either ECG detection or self-report, was estimated according to sampling weights, non-response and age and sex distribution of the population. We used multivariable logistic regression to estimate associations among sociodemographic, clinical and geographic factors with the AF prevalence, awareness and treatment.
Results
The weighted AF prevalence was 1.8% (95% CI 1.7% to 1.9%), but varied from 0.9% to 2.4% across geographical regions and equates to being present in an estimated 7.9 (95% CI 7.4 to 8.4) million people in China. Among men and women, the AF prevalence increased from 0.8% and 0.6% in the age group 45-54 years to 5.4% and 4.9% in the age group ≥75 years, respectively. Proportions of people who were aware of having AF decreased overall from 65.3% in 45-54 year-olds to 53.9% in ≥75 year-olds and varied between sex (men 58.5%, women 68.8%) and residency status (urban 78.3%, rural 35.3%). Only 6.0% of patients with high-risk AF received anticoagulation therapy.
Conclusions
AF prevalence is higher than previously reported in China, with low awareness and large treatment gaps. Large-scale efforts are urgently needed to reduce AF adverse consequences.

© 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: 27 Jan 2021; epub ahead of print
Du X, Guo L, Xia S, Du J, ... Dong J, Ma C
Heart: 27 Jan 2021; epub ahead of print | PMID: 33509976
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Abstract

Development of an electrocardiogram-based risk calculator for a cardiac cause of syncope.

Zimmermann T, du Fay de Lavallaz J, Walter JE, Strebel I, ... Mueller C, BASEL IX and SRS Investigators
Objective
To develop an ECG-based tool for rapid risk assessment of a cardiac cause of syncope in patients ≥40 years.
Methods
In a prospective international multicentre study, 2007 patients ≥40 years presenting with syncope were recruited in the emergency department (ED) of participating centres ranging from large university hospitals to smaller rural hospitals in eight countries from May 2010 to July 2017. 12-Lead ECG recordings were obtained at ED presentation following the syncopal event. The primary diagnostic outcome, a cardiac cause of syncope, was centrally adjudicated by two independent cardiologists using all available clinical information including 12-month follow-up. ECG predictors for a cardiac cause of syncope were identified using penalised backward selection and a continuous-scale likelihood was calculated based on regression analysis coefficients. Findings were validated in an independent US multicentre cohort including 2269 patients.
Results
In the derivation cohort, a cardiac cause of syncope was adjudicated in 267 patients (16%). Seven ECG criteria were identified as predictors for this outcome: heart rate and QTc-interval (continuous predictors), rhythm, atrioventricular block, ST-segment depression, bundle branch block and ventricular extrasystole/non-sustained ventricular tachycardia (categorical predictors). Diagnostic accuracy of these combined predictors for a cardiac cause of syncope was high (area under the curve 0.80, 95% CI 0.77 to 0.83). Overall, 138 patients (8%) were rapidly triaged towards rule-out and 181 patients (11%) towards rule-in of a cardiac cause of syncope. External validation showed similar performance.
Conclusion
In patients ≥40 years with a syncopal event, a combination of seven ECG criteria enabled rapid assessment of the likelihood that syncope was due to a cardiac cause.
Trial registration number
NCT01548352 (BASEL IX), NCT01802398 (SRS study).

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

Heart: 26 Jan 2021; epub ahead of print
Zimmermann T, du Fay de Lavallaz J, Walter JE, Strebel I, ... Mueller C, BASEL IX and SRS Investigators
Heart: 26 Jan 2021; epub ahead of print | PMID: 33504514
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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: 26 Jan 2021; epub ahead of print
Bossard M, Gao P, Boden W, Steg G, ... Yusuf S, Mehta SR
Heart: 26 Jan 2021; epub ahead of print | PMID: 33504513
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Abstract

Individual non-esterified fatty acids and incident atrial fibrillation late in life.

Pellegrini CN, Buzkova P, Lichtenstein AH, Matthan NR, ... Djoussé L, Kizer JR
Objective
Obesity and dysmetabolism are major risk factors for atrial fibrillation (AF). Expansion of fat depots is associated with increased circulating total non-esterified fatty acids (NEFAs), elevated levels of which are associated with incident AF. We undertook comprehensive serum measurement of individual NEFA to identify specific associations with new-onset AF late in life.
Methods
The present study focused on participants with available serum and free of AF selected from the Cardiovascular Health Study, a community-based longitudinal investigation of older US adults. Thirty-five individual NEFAs were measured by gas chromatography. Cox regression was used to evaluate the association of individual NEFAs with incident AF.
Results
The study sample included 1872 participants (age 77.7±4.4). During median follow-up of 11.3 years, 715 cases of incident AF occurred. After concurrent adjustment of all NEFAs and full adjustment for potential confounders, higher serum concentration of nervonic acid (24:1 n-9), a long-chain monounsaturated fatty acid, was associated with higher risk of AF (HR per SD: 1.18, 95% CI 1.08 to 1.29; p<0.001). Conversely, higher serum concentration of gamma-linolenic acid (GLA) (18:3 n-6), a polyunsaturated n-6 fatty acid, was associated with lower risk of AF (HR per SD: 0.81, 95% CI 0.71 to 0.94; p=0.004). None of the remaining NEFAs was significantly associated with AF.
Conclusions
Among older adults, serum levels of non-esterified nervonic acid were positively associated, while serum levels of non-esterified GLA were inversely associated, with incident AF. If confirmed, these results could offer new strategies for AF prevention and early intervention in this segment of the population at highest risk.

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

Heart: 21 Jan 2021; epub ahead of print
Pellegrini CN, Buzkova P, Lichtenstein AH, Matthan NR, ... Djoussé L, Kizer JR
Heart: 21 Jan 2021; epub ahead of print | PMID: 33483356
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Abstract

A stand-alone structured educational programme after myocardial infarction: a randomised study.

Giannopoulos G, Karageorgiou S, Vrachatis D, Anagnostopoulos I, ... Cleman M, Deftereos S
Background
Acute myocardial infarction (MI) is a major clinical manifestation of coronary artery disease. Post-MI morbidity and mortality can be reduced by lifestyle changes and aggressive risk factor modification. These changes can be applied more effectively if the patient is actively involved in the process. The hypothesis of this study was that an educational programme in post-MI patients could lead to reduced incidence of cardiovascular events.
Methods
Post-MI patients were prospectively randomised into two groups. Patients in the intervention arm were scheduled to attend an 8-week-long educational programme on top of usual treatment, while controls received optimal treatment. The primary endpoint was the composite of all-cause death, MI, cerebrovascular event and unscheduled hospitalisation for cardiovascular causes. Endpoint adjudication was blinded.
Results
329 patients (238 men) were included, with a mean follow-up time of 17±4 months. In the primary analysis, mean primary end point-free survival time was 597 days (95% CI 571 to 624) in controls, compared with 663 days (95% CI 638 to 687) in the intervention group (p<0.001). The HR in the univariate Cox regression analysis was 0.48 (95% CI 0.32 to 0.73; p=0.001). The raw rates of the primary endpoint were 20.8% (6 deaths, 13 MIs, 2 strokes and 14 hospitalisations) vs 36.6% (8 deaths, 22 MIs, 7 strokes and 22 hospitalisations), respectively (OR 0.46, 95% CI 0.28 to 0.74; p=0.002).
Conclusion
These results suggest that a relatively short adult education programme offered to post-MI patients has beneficial effects, resulting in reduced risk of cardiovascular events.
Trial registration number
NCT04007887.

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

Heart: 21 Jan 2021; epub ahead of print
Giannopoulos G, Karageorgiou S, Vrachatis D, Anagnostopoulos I, ... Cleman M, Deftereos S
Heart: 21 Jan 2021; epub ahead of print | PMID: 33483355
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Abstract

Socioeconomic position and cardiovascular mortality in 63 million adults from Brazil.

Mallinson PAC, Luhar S, Williamson E, Barreto ML, Kinra S
Background
It has been suggested that cardiovascular disease exhibits a \'social cross-over\', from greater risk in higher socioeconomic groups to lower socioeconomic groups, on economic development, but robust evidence is lacking. We used standardised data to compare the social inequalities in cardiovascular mortality across states at varying levels of economic development in Brazil.
Methods
We used national census and mortality data from 2010. We used age-adjusted multilevel Poisson regression to estimate the association between educational status and cardiovascular mortality by state-level economic development (assessed by quintiles of Human Development Index).
Results
In 2010, there were 185 383 cardiovascular deaths among 62.5 million adults whose data were analysed. The age-adjusted cardiovascular mortality rate ratio for women with <8 years of education (compared with 8+ years) was 3.75 (95% CI 3.29 to 4.28) in the least developed one-fifth of states and 2.84 (95% CI 2.75 to 2.92) in the most developed one-fifth of states (p value for linear trend=0.002). Among men, corresponding rate ratios were 2.53 (95% CI 2.32 to 2.77) and 2.26 (95% CI 2.20 to 2.31), respectively (p value=0.258). Associations were similar across subtypes of cardiovascular disease (ischaemic heart disease and stroke) and robust to the size of geographical unit used for analysis.
Conclusions
Our results do not support a \'social crossover\' in cardiovascular mortality on economic development. Our analyses, based on a large standardised dataset from a country that is currently experiencing economic transition, provide strong evidence that low socioeconomic groups experience the highest risk of cardiovascular disease, irrespective of the stage of national economic development.

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

Heart: 21 Jan 2021; epub ahead of print
Mallinson PAC, Luhar S, Williamson E, Barreto ML, Kinra S
Heart: 21 Jan 2021; epub ahead of print | PMID: 33483354
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Abstract

Nuclear cardiology: state of the art.

Schofield R, Menezes L, Underwood SR
Radionuclide imaging remains an essential component of modern cardiology. There is overlap with the information from other imaging techniques, but no technique is static and new developments have expanded its role. This review focuses on ischaemic heart disease, heart failure, infection and inflammation. Radiopharmaceutical development includes the wider availability of positron emission tomography (PET) tracers such as rubidium-82, which allows myocardial perfusion to be quantified in absolute terms. Compared with alternative techniques, myocardial perfusion scintigraphy PET and single photon emission computed tomography (SPECT) have the advantages of being widely applicable using exercise or pharmacological stress, full coverage of the myocardium and a measure of ischaemic burden, which helps to triage patients between medical therapy and revascularisation. Disadvantages include the availability of expertise in some cardiac centres and the lack of simple SPECT quantification, meaning that global abnormalities can be underestimated. In patients with heart failure, despite the findings of the STICH (Surgical Treatment for Ischemic Heart Failure) trial, there are still data to support the assessment of myocardial hibernation in predicting when abolition of ischaemia might lead to improvement in ventricular function. Imaging of sympathetic innervation is well validated, but simpler markers of prognosis mean that it has not been widely adopted. There are insufficient data to support its use in predicting the need for implanted devices, but non-randomised studies are promising. Other areas where radionuclide imaging is uniquely valuable are detection and monitoring of endocarditis, device infection, myocardial inflammation in sarcoidosis, myocarditis and so on, and reliable detection of deposition in suspected transthyretin-related amyloidosis.

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

Heart: 21 Jan 2021; epub ahead of print
Schofield R, Menezes L, Underwood SR
Heart: 21 Jan 2021; epub ahead of print | PMID: 33483353
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Abstract

Sex differences in mapping and rhythm outcomes of a repeat atrial fibrillation ablation.

Pak HN, Park JW, Yang SY, Kim M, ... Joung B, Lee MH
Objective
The risk of procedure-related complications and rhythm outcomes differ between men and women after atrial fibrillation catheter ablation (AFCA). We evaluated whether consistent sex differences existed in mapping and rhythm outcomes in repeat ablation procedures.
Methods
Among 3282 patients in the registry, we analysed 443 consecutive patients (24.6% female, 58.5±10.3 years old, 61.5% with paroxysmal atrial fibrillation) who underwent a second AFCA. We compared the clinical factors, mapping, left atrial (LA) pressure, complications and long-term clinical recurrences after propensity score matching.
Results
LA volume index (43.1±18.6 vs 35.8±11.6 mL/m2, p<0.001) was higher, but LA dimension (40.0±6.8 vs 41.6±6.3 mm, p=0.018), LA voltage (0.94±0.55 vs 1.20±0.68 mV, p=0.002) and pericardial fat volume (89.5±43.1 vs 122.1±53.9 cm3, p<0.001) were lower in women with repeat ablation than in their male counterparts. Pulmonary vein (PV) reconnections were lower (58.7% vs 74.9%, p=0.001), but the proportion of extra-PV triggers (27.5% vs 17.0%, p=0.026) and elevated LA pulse pressures (79.7% vs 63.7%, p=0.019) was significantly higher in women than in men. There was no significant sex difference in the rate of procedure-related complications (4.6% vs 4.2%, p=0.791). During a 31-month (8-60) median follow-up, clinical recurrences were significantly higher in women after both the de novo procedure (log-rank p=0.039, antiarrhythmic drug (AAD)-free log-rank p<0.001) and the second procedure (log-rank p=0.006, AAD-free log-rank p=0.093). Female sex (HR 1.51, 95% CI 1.06 to 2.15, p=0.023), non-paroxysmal atrial fibrillation (HR 1.78, 95% CI 1.30 to 2.34, p<0.010) and extra-PV triggers (HR 1.88, 95% CI 1.28 to 2.75, p=0.001) were independently associated with clinical recurrences after repeat procedures.
Conclusions
During repeat AFCA procedures, PV reconnections were lower in women than in men, and the existence of extra-PV triggers and an LA pressure elevation were more significant, which resulted in poor rhythm outcomes.
Trial registration number
NCT02138695.

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

Heart: 21 Jan 2021; epub ahead of print
Pak HN, Park JW, Yang SY, Kim M, ... Joung B, Lee MH
Heart: 21 Jan 2021; epub ahead of print | PMID: 33483352
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This program is still in alpha version.