BACKGROUND:Nationwide studies report the high incidence of major health outcomes following myocardial infarction (MI). This cohort study investigates variation in incidence of health outcomes following MI between health commissioning areas within England. METHODS:All adults ≥18 years of age with index MI admitted to hospital within all 106 integrated care board (ICB) subpopulations in England were included (2008-2017). The cumulative incidence of all-cause mortality and non-fatal health outcomes (subsequent MI and first hospitalisation for heart failure, atrial fibrillation, cerebrovascular disease, peripheral arterial disease, severe bleeding, renal failure, diabetes mellitus and depression) within 9 years of follow-up was calculated from flexible parametric survival models adjusted for age, sex, year of MI and deprivation. Choropleth maps and funnel plots were used to visualise the degree of variation in incidence of outcomes by ICB subpopulation. The intraclass correlation coefficient (ICC) was used to determine the degree of variation explained at the area versus patient level. RESULTS:A total of 381 518 individuals with MI (n=2 807 195 hospital admissions) were included in the study. The crude incidence of post-MI health outcomes varied between areas, including heart failure (range 20.2%-47.9%), severe bleeding (14.3%-34.6%), renal failure (23.7%-38.0%) and all-cause mortality (34.3%-47.7%). The incidence of each major health outcome following MI fell within expected range (between 95% control limits) after adjusting for patient demographics with the exception of two sub-ICBs in Lancashire and South Cumbria, where rates were higher than expected. Overall, variation observed was predominantly explained by region-specific patient demographic profiles rather than at the ICB subpopulation level (ICC <5% for all outcomes). CONCLUSIONS:This research provides region-specific data for the incidence of 10 major health outcomes following MI in England. The findings can support commissioners to target resources to those areas with populations at greatest risk of major health outcomes following MI.
BACKGROUND:N-terminal pro-B-type natriuretic peptide (NT-proBNP) is a well-established biomarker for cardiovascular risk; however, its prognostic value in patients with atrial fibrillation (AF) who are not receiving anticoagulation therapy has not been well established. We investigated the association between NT-proBNP levels, clinical characteristics and cardiovascular outcomes in non-anticoagulated patients with AF and assessed whether baseline heart rhythm modified these associations. METHODS:Plasma samples were obtained at baseline in two multicentre clinical trials involving 3183 patients with AF randomised to aspirin with a median follow-up of 18 months. NT-proBNP was analysed using the Elecsys immunoassay. Associations between NT-proBNP and clinical characteristics were assessed by multivariable linear regression. Associations with clinical outcomes were evaluated using Cox regression models. The prognostic value of NT-proBNP was evaluated with C-statistics. RESULTS:AF on the baseline ECG was the clinical factor most strongly associated with NT-proBNP levels, with concentrations 4.2 times higher in AF than in sinus rhythm. NT-proBNP was independently associated with ischaemic stroke (the third sample quartile compared with the first, HR 2.07, 95% CI 1.46 to 2.94), heart failure hospitalisation (HR 2.16, 95% CI 1.59 to 2.92), cardiovascular death (HR 2.43, 95% CI 1.79 to 3.30) and all-cause death (HR 2.09, 95% CI 1.65 to 2.65) during follow-up. There was no interaction between heart rhythm and the associations between NT-proBNP and outcomes (all p values ≥0.07). CONCLUSIONS:In non-anticoagulated patients with a diagnosis of AF, NT-proBNP levels were significantly associated with the risk of clinical outcomes. Baseline AF rhythm was the clinical factor most strongly associated with NT-proBNP levels. However, the associations between NT-proBNP and outcomes remained consistent regardless of baseline rhythm.
Background General practitioners (GPs) have limited tools for chest pain patients to identify (non-)obstructive coronary artery disease (OCAD). This trial evaluates whether GP access to the coronary artery calcium score (CACS) improves diagnostic efficiency and cardiovascular risk management (CVRM). Methods COroNary Calcium scoring as fiRst-linE Test to dEtect and exclude coronary artery disease in GP patients with stable chest pain (CONCRETE) is a pragmatic, non-blinded implementation study that cluster-randomised 101 Dutch GP offices into CACS or standard of care (SOC). Patients aged ≥40 (men) or ≥45 (women) years, without known CAD, with possible cardiac or non-cardiac chest pain were included. The primary outcome was the proportional 2-year increase in CVRM registrations at GP office level. Patient-level secondary outcomes included cardiologist referral rate, OCAD diagnosis and CVRM enrolment. Results At GP office level, no significant difference in CVRM registration increase was seen for CACS versus SOC (46 CACS practices: +0.3%, 45 SOC practices: +0.2%, p=0.77). Per protocol analysis for patient-level outcomes included 583 patients (57.5% women, mean age 60.6±9.1 years) (CACS arm: 466; SOC arm: 117), recruited between January 2019 and October 2023. The CACS arm showed 47.1% relative reduction in cardiologist referrals compared with SOC (42.5% vs 80.3%; modelled difference 31.3% (95% CI 14.8% to 47.8%)). OCAD detection rates were not significantly different (CACS: 4.9, SOC: 7.7%, p=0.14). Patients with higher CACS had a higher probability of cardiologist referral (from 8.4% for CACS 0 to 94.2% for CACS ≥400, difference +85.7% (95% CI 79.4% to 91.9%)) and of OCAD diagnosis (0% for CACS 0 to 21.2% for CACS ≥400, OR 9.08 (95% CI 4.20 to 19.67)). Compared with SOC, more CACS patients were enrolled in CVRM (36.3% vs 17.0%, p<0.01). Conclusions In this pragmatic, primary-care implementation and proof-of-concept trial, CACS was an effective diagnostic test for stable chest pain patients with (very) low likelihood of OCAD. CACS reduced unnecessary cardiology referrals and enhanced individual preventive care, without demonstrable practice-level impact on CVRM registrations. Registration The CONCRETE study is registered under CCMO Register NL66821.042.18 and closed for enrolment.
Despite recent advances in prevention and treatment, cardiovascular disease (CVD) remains a leading cause of premature death and disability globally, with a rising burden in many low- and middle-income countries. Several modifiable determinants of CVD are well-established (eg, smoking, hypertension, obesity, dyslipidaemia), but they do not fully explain temporal trends and large variations in disease rates between different populations. Moreover, the causal relevance of certain CVD risk factors and/or their associated biological mechanisms is still incompletely understood. High-throughput affinity-based proteomic assays now enable quantification of several thousand protein markers in the blood, and their application in large epidemiological and clinical studies will facilitate the development of precision cardiovascular medicine. This review describes recent findings from large population-based studies to illustrate the value of proteomics in cardiology for improved risk prediction, diagnosis and patient stratification; better understanding of disease aetiology and pathophysiology; and identification of repurposing and novel therapeutic targets. To overcome the current limitations, future studies should aim to further increase the sample size, number of proteins measured reliably (eg, via multiple assay platforms) and longitudinally, and ancestry population diversity, to expedite clinical translation of key research findings that will help to transform development of precision medicine in cardiology globally.
BACKGROUND:The role of blood pressure (BP) lowering in patients with heart failure (HF) with mildly reduced or preserved ejection fraction (HFmrEF/HFpEF) remains uncertain, and it is unclear to what extent the existing benefits of therapies are mediated by BP reduction. METHODS AND RESULTS:A systematic review and meta-analysis of randomised clinical trials was conducted, comparing any BP lowering treatment to placebo, usual care or another drug class in patients with HFmrEF/HFpEF. The primary endpoint was a composite of cardiovascular death and HF hospitalisation. Data were pooled using a random effects meta-analysis and meta-regression with inverse variance weighting expressed as a risk ratio (RR) and its 95% CI. 18 studies were identified totalling 39 452 patients. Pharmacological BP lowering led to a significant reduction in the primary composite endpoint (RR 0.86, 95% CI 0.83 to 0.89; p≤0.001), but there were significant differences between drug classes (p value=0.018), with evidence of benefit with sodium-glucose cotransporter 2 inhibitor, mineralocorticoid receptor antagonist, angiotensin-receptor neprilysin inhibitor and glucagon-like peptide-1 receptor agonists but not other drug classes. Meta-regressions found no significant association between the degree of BP reduction and treatment effects (coefficient slope=-0.0125, p=0.304). Similarly, pharmacological BP lowering was associated with a reduction in HF hospitalisations (RR 0.83, 95% CI 0.79 to 0.86; p≤0.001), but treatment effects were not related to degree of BP reduction (coefficient slope=-0.0121, p=0.528). CONCLUSION:In patients with HFmrEF/HFpEF, there was no significant association between pharmacological BP lowering and clinical outcomes, suggesting that BP lowering alone is unlikely to explain all the benefits observed with the use of recently established HF therapies. PROSPERO REGISTRATION NUMBER:CRD42025631539.
Heart failure (HF) and cancer are leading causes of global morbidity and mortality that share a significant bidirectional relationship. Epidemiologic studies reveal that cancer patients and survivors face a substantially elevated risk of HF, largely driven by cardiotoxic systemic therapies including chemotherapy, targeted therapy, immunotherapy and radiation therapy. Conversely, individuals with HF have a markedly increased incidence of cancer. This interconnection is underpinned by age and shared modifiable risk factors, including smoking, hypertension, diabetes and obesity, as well as common pathophysiological mechanisms such as chronic inflammation, neurohormonal activation, oxidative stress and dysregulated angiogenesis. Clonal haematopoiesis of indeterminate potential has emerged as a novel biological link, promoting both maladaptive cardiac remodelling and tumourigenesis. Clinically, the coexistence of HF and cancer creates complex management challenges, as each condition worsens the prognosis of the other and limits therapeutic options. In addition to providing a broad overview of the topic, this review incorporates three aspects that are underexplored in existing cardio-oncology literature-management of advanced metastatic cancer in patients with HF, use of advanced HF therapies in patients with cancer and disparities in cardio-oncology care and clinical trial representation. Effective management of patients with HF and cancer requires a multidisciplinary cardio-oncology approach that incorporates rigorous risk stratification, early detection using serial cardiac biomarkers and imaging and personalised management tailored to cancer treatment. Irrespective, cancer patients with HF have a poor prognosis. It is necessary to balance oncological efficacy with cardiovascular safety while providing a clear definition of the goals of care. Early integration of palliative and rehabilitative care can significantly improve patient quality of life and outcomes. Nevertheless, effective novel treatment strategies have significantly improved the overall survivorship for patients with cancer and/or HF.
BACKGROUND AND OBJECTIVES:Implantable cardioverter defibrillator (ICD) therapy is indicated following a myocardial infarction (MI) to curtail the risk of sudden cardiac death (SCD) in patients who are classified as high-risk, defined by a left ventricular ejection fraction (LVEF) ≤35%. The understanding of risk in patients with ischaemic injury who do not meet these criteria is limited. This study aims to assess the burden of SCD in patients' post-MI with LVEF 36-50%. METHODS:Articles reporting mortality and SCD outcomes for participants with LVEF 36-50% post-MI without additional risk stratification or intervention were included. Medline, Embase and Cochrane databases were searched from index entries until the present. Data were synthesised using a random-effects model. Competing risk adjusted number needed to treat (NNT) for ICD implantation was calculated. This study adheres to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. RESULTS:7435 records were identified, five studies with 9345 patients were included. The pooled annual rate of SCD in patients with LVEF 36-50% post-MI was 1.74% (95% CI 1.02 to 2.95); a higher annual rate of 6.34% was observed for LVEF≤35% (p=0.03) while a lower yearly rate of 0.55% was observed for LVEF >50% (p=0.02). The proportion of mortality due to SCD was similar across all LVEF strata (p=0.79). Very high between-study heterogeneity was observed (I2=89.9% for SCD and I2=96.8% for all-cause mortality). During exploratory modelling, the primary prevention ICD NNT for patients with LVEF 36-50% was 19 when applying the MADIT-II ICD treatment effect (HR 0.33, 95% CI 0.20 to 0.53) and extrapolation to a 5-year device lifespan. CONCLUSION:This is the first meta-analysis reviewing post-MI patients with LVEF 36-50%. These findings highlight a clinically relevant unmet need for patients who carry a substantial burden of SCD despite being outside current ICD eligibility criteria. Further study is needed to improve risk stratification within this population and determine whether suitable intervention is beneficial. PROSPERO REGISTRATION NUMBER:CRD42024551830.
BACKGROUND:Whether mineralocorticoid receptor antagonists (MRAs) confer incremental clinical benefit in patients with transthyretin amyloid cardiomyopathy (ATTR-CM) treated with disease-modifying therapy remains uncertain. We aimed to assess the effectiveness and safety of MRAs in patients with ATTR-CM receiving disease-modifying therapy. METHODS:This retrospective cohort study used data from the TriNetX US database to identify adult patients with ATTR-CM who initiated disease-modifying therapy (tafamidis or vutrisiran) within 1 year of incident heart failure (HF) diagnosis between 1 September 2019 and 10 December 2025. Patients were categorised as MRA users or non-users and were matched based on 1:1 propensity-score matching. The primary effectiveness endpoint was a composite of all-cause mortality or HF hospitalisation (HFH). Secondary effectiveness endpoints were all-cause mortality, HFH and ventricular arrhythmia (VA). The safety endpoint was hyperkalaemia. RESULTS:Among 4598 patients with ATTR-CM (mean (SD) age, 77.6 (8.4) years; 3726 (81.0%) men) treated with tafamidis (n=4386) or vutrisiran (n=377), 505 MRA users were matched to 505 non-users. MRA use was not associated with significant reductions in all-cause mortality or HFH (HR 1.04; 95% CI 0.82 to 1.32; p=0.73). There was no significant difference in all-cause mortality (HR 1.00; 95% CI 0.70 to 1.46; p=0.96), HFH (HR 1.09; 95% CI 0.84 to 1.43; p=0.48) and VA (HR 1.07; 95% CI 0.77 to 1.48; p=0.67). Hyperkalaemia was not significantly higher in MRA users (HR 1.13; 95% CI 0.89 to 1.44; p=0.29) compared with non-users. CONCLUSIONS:In a contemporary cohort of patients with ATTR-CM treated with disease-modifying therapy, MRA use was associated with limited incremental clinical benefits.
BACKGROUND:The mechanisms underlying stroke recurrence after patent foramen ovale (PFO) closure for secondary prevention remain poorly understood. This study evaluated incomplete device apposition (IDA) using cardiac CT angiography (CTA) and investigated its association with stroke recurrence. METHODS:In this prospective cohort study conducted at four centres in China (2020-2026), 233 patients (mean age: 37.01±6.73 years; 48.9% male) without known vascular risk factors were included from 382 consecutive candidates who underwent transcatheter PFO closure with follow-up ≥6 months. Cardiac CTA at 6 months post closure assessed the presence, location and extent of IDA defined as a gap between the left disc and the interatrial septum. Recurrent stroke and new-onset symptoms (atrial tachyarrhythmia, migraine headache, chest pain/discomfort) were recorded and their associations with IDA were analysed. RESULTS:IDA was observed in 55.8% of patients predominantly at the anterior-inferior rim (93.4%). IDA was significantly associated with larger and longer PFOs, larger devices and greater in vivo device thickness (p < 0.001 for all). During a median follow-up of 20.00 (IQR 18.00-24.00) months, patients with IDA had a higher risk of recurrent stroke (log-rank p = 0.022) and new-onset symptoms (log-rank p < 0.001). In eight patients who underwent repeat CTA, device apposition remained stable after 6-month closure. Pathological validation was available in one patient with severe chest pain/discomfort and a well-apposed device had sufficient endothelialisation. CONCLUSION:IDA is common after PFO closure and is associated with increased risks of recurrent stroke and new-onset symptoms. Preventive strategies warrant further investigation. TRIAL REGISTRATION NUMBER:NCT04686253.
BACKGROUND:Data regarding the association between self-expandable transfemoral transcatheter aortic valve replacement (TF-TAVR) and pure native aortic regurgitation (PNAR) are limited. The authors described their initial experience with self-expandable TF-TAVR for the treatment of patients with PNAR from the NTCVR database in China. METHODS:This was a national registry-based, multicentre, retrospective cohort study. Patients with PNAR were enrolled from the NTCVR in China between January 2017 and December 2023. The primary endpoint event was all-cause mortality at 30 days. Logistic regression analysis and machine learning techniques were used to identify the risk factors associated with 30-day all-cause mortality of TF-TAVR in patients with PNAR. RESULTS:Total 890 patients with PNAR (mean age 73.2 years; 56.3% men) from 72 centres in China were enrolled in this study. The in-hospital and 30-day all-cause mortality were 2.0% and 2.7%, respectively. By multivariate logistic regression analysis, the diameter of the ascending aorta (OR, 1.103 (95% CI 1.005 to 1.212); p=0.039) and renal insufficiency (OR, 4.602 (95% CI 1.455 to 14.553); p=0.009) were associated with the 30-day all-cause mortality. Moreover, Shapley Additive explanations analysis for the machine learning model XGBoost also highlighted the diameter of the ascending aorta as the key predictor; patients with an ascending aorta greater than 41.6 mm had a significantly higher 30-day all-cause mortality rate (OR, 5.027 (95% CI 2.042 to 12.696); p=0.0004). Moreover, the NYHA class III/IV and annulus long diameter were predictors of technical success in multivariate analysis. CONCLUSION:In this large national registry-based observational and exploratory study, we identified the ascending aorta as the key predictor for PNAR patients who underwent self-expandable TF-TAVR. Patients with ascending aortic diameters greater than 41.6 mm may have a significantly higher 30-day all-cause mortality rate.
Syncope is a common clinical problem affecting up to 40% of individuals over a lifetime. Most cases, especially neurocardiogenic (ie, vasovagal, reflex-mediated) syncope, are benign. However, cardiac causes, accounting for roughly 10%, carry a significantly higher risk of morbidity and mortality, underscoring the need for timely diagnosis and management. Accordingly, this review focuses primarily on the evaluation and management of cardiac syncope. The cornerstone of evaluation for any patient presenting with syncope remains a detailed history and physical examination, which guide selective use of diagnostic testing such as echocardiography, ambulatory monitoring and exercise testing. Routine indiscriminate testing offers limited diagnostic yield while significantly increasing cost. Decisions regarding hospital admission should be individualised based on risk features, stability and availability of close outpatient follow-up, as not all admissions improve outcomes. Treatment strategies vary depending on aetiology. Emerging technologies including artificial intelligence and wearable devices offer promise for improving diagnosis, risk stratification and monitoring. Future research should focus on refining admission criteria, optimising diagnostic pathways and validating novel digital and interventional approaches to enhance individualised care for patients with suspected cardiac syncope.
BACKGROUND:Exercise has the potential to unmask ventricular arrhythmias in arrhythmogenic cardiomyopathy (ACM). The aim of the study was to assess the prevalence and prognostic significance of exercise-induced ventricular arrhythmias (EIVAs) during exercise tests. METHODS:Clinical data of patients with a definitive diagnosis of ACM as well as individuals harbouring a pathogenic or likely pathogenic (P/LP) gene variant associated with ACM who exhibited a negative or borderline phenotype were retrospectively analysed. Patients were stratified into 'lower' and 'higher' exercise groups based on exercise intensity performed after the diagnosis. EIVAs were adjudicated on revision of the exercise test (exercise tolerance test (ETT) or cardiopulmonary exercise test (CPET)). Peak VO2 was obtained via CPET or estimated from metabolic equivalents. The primary endpoint was a composite of sustained ventricular tachycardia/fibrillation, appropriate implantable cardioverter-defibrillator therapy, sudden cardiac arrest and sudden death. RESULTS:Of 202 patients followed at our centre, 157 (mean age 48±16 years, 57% men) underwent ETT or CPET at baseline; 80 (51%) patients harboured a P/LP variant, most commonly in plakophilin-2 (n=43), desmoplakin (n=18) and filamin C (n=11) genes. Mean peak VO2 was 41.4±10.6 mL/kg/min. EIVAs were observed in 61 (39%) cases. Patients demonstrating EIVA exhibited lower peak VO2 (38.2 ± 10.2 vs 43.0 ± 10.4 mL/kg/min, p=0.019) and a numerically higher prevalence of myocardial fibrosis (MF) on cardiac magnetic resonance (52% vs 37%, p=0.071) with respect to counterparts. Among 65 patients with a baseline normal ECG, 9 (14%) exhibited EIVA; among 29 genotype-positive individuals with a negative or borderline phenotype, 6 (20%) showed EIVA. The prevalence of EIVA was comparable between the lower-exercise and higher-exercise groups (31% vs 30%, respectively). MF (HR 6.05, 95% CI 1.70 to 21.54; p=0.005) and EIVA (HR 2.8, 95% CI 1.1 to 7.3; p=0.03) were independently associated with the primary arrhythmic endpoint at multivariable analysis, with similar direction of effect after accounting for beta-blocker therapy in sensitivity analyses. The combination of the two risk factors-EIVA and MF (score 2) significantly stratified prognosis in comparison to none or one risk factor (score 0-1), p<0.001. CONCLUSIONS:EIVAs occurred in nearly 40% of patients with ACM and were associated with adverse arrhythmic outcomes, alongside MF. These findings support the integration of exercise testing into routine risk stratification.
