Heart最新文献

Intravenous thrombolytics remain the mainstay of treatment for ischaemic stroke and retain importance for selected patients with ST-elevation myocardial infarction and pulmonary embolism. Pharmacological and practical advantages of the fibrinolytic tenecteplase have recently led to a widespread shift in ischaemic stroke management. Meta-analysis of randomised trials demonstrated superiority of tenecteplase over alteplase in achieving excellent functional outcome after stroke (no disability). Trials have also extended the time window for thrombolytics in stroke to 24 hours, provided imaging demonstrates salvageable brain tissue. Although endovascular therapy is the most effective treatment for large vessel occlusion stroke, access remains limited to major metropolitan centres in developed nations. Trials suggest that thrombolytics add value, even in patients receiving endovascular therapy, and for many patients globally, intravenous thrombolytics are the only accessible reperfusion treatment. Tenecteplase is established as the preferred thrombolytic for selected patients with ST-elevation myocardial infarction, generally reserved for patients who cannot rapidly access percutaneous intervention following first medical contact. Notably, the dose used is twice that for stroke. Pre-hospital delivery of tenecteplase by paramedics is an important strategy in rural and remote areas. While patients with high-risk pulmonary embolism benefit from systemic thrombolysis, adjunctive tenecteplase in intermediate-risk pulmonary embolism has been associated with increased risk of major bleeding and haemorrhagic stroke. The practical advantages of bolus administration and having a single thrombolytic on formulary for all relevant indications have positioned tenecteplase as the leading thrombolytic agent in current practice. This review discusses the current evidence and treatment guidelines in this rapidly evolving field.

Background: Heart failure (HF) imposes a major health burden on women. While traditional (well-established) risk factors are well studied, less attention has been given to psychosocial, environmental and female-specific reproductive risk factors. This study quantifies the contribution of these risk domains to incident HF in women.

Methods: We included 233 125 women from the UK Biobank with a median follow-up of 13.7 years. 22 risk factors were grouped as well-established (eg, hypertension), under-recognised (eg, depression, socioeconomic deprivation) or female-specific (eg, early age at menopause, parity). Cox regression models and population attributable fractions (PAFs) were used to estimate HF risk and burden. Analyses were stratified by age and obesity.

Results: A total of 6077 women developed HF. The overall PAF for all risk factors was 66.0%. Hypertension had the largest individual contribution (PAF 25.3%). Well-established, under-recognised and female-specific risk factors accounted for 46.0%, 25.5% and 15.5% of HF cases, respectively. Chronic inflammatory diseases, early age at menopause and early age at first birth were key reproductive drivers. Age-stratified analyses showed the highest HF burden in women aged 55-59 years (PAF 70.0%).

Conclusion: A combination of modifiable, psychosocial, environmental and reproductive risk factors accounts for two-thirds of HF cases in women. Tailored, life course-oriented prevention strategies are essential to reduce this burden.

Background: Chronic kidney disease is common in patients with coronary artery disease (CAD) and can significantly affect drug excretion and efficacy. This study focuses on the effects of modification of renal function on platelet aggregation.

Methods: In total, 164 patients with stable CAD undergoing dual antiplatelet therapy were enrolled and randomised to receive either 75 mg clopidogrel or 3.75 mg prasugrel daily. Patients were stratified based on estimated glomerular filtration rate (eGFR) into two groups: eGFR <45 (eGFR <45 group) or ≥45 mL/min/1.73 m² (eGFR ≥45 group). The primary endpoint was the inhibition of platelet aggregation on day 5 and day 30. Analysis of covariance was performed to compare the P2Y₁₂ reaction units (PRU) on days 5 and 30 after randomisation.

Results: In the eGFR <45 group, prasugrel induced a more rapid decrease in platelet aggregation than clopidogrel. Mean PRU value for clopidogrel and prasugrel at baseline, day 5 and day 30 was 198.2 vs 177.2, 214.2 vs 157.9 and 200.0 vs 141.7, respectively. The differences were statistically significant on day 5 (p=0.036), but not on day 30 (p=0.105). The p for interaction between treatment effect and eGFR was 0.498 at baseline, 0.028 at day 5 and 0.212 at day 30, emphasising that the drug effect was significantly different by kidney function, but only in the early phase of drug initiation.

Conclusion: In patients with impaired renal function, prasugrel provided a more rapid reduction in platelet aggregation compared with clopidogrel, particularly during the early phase of antiplatelet treatment. Further research is needed to confirm these findings in larger and more diverse populations.

Trial registration number: URL: https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000027055; Unique identifier: UMIN000023489.

Background: Acute coronary syndrome (ACS) is a global leading cause of morbidity, with residual inflammation contributing to recurrent events. Colchicine has been proposed as an adjunct therapy, but its efficacy remains uncertain.

Methods: We performed a systematic review and meta-analysis. PubMed, Embase and Cochrane databases were searched for randomised controlled trials (RCTs) data comparing colchicine versus placebo in ACS. Risk ratio (RR) and mean difference with 95% CIs were computed for binary and continuous outcomes, respectively. Primary outcomes were adverse cardiovascular events (ACEs), mortality and safety. Random-effects models were used for pooled estimates.

Results: Seventeen RCTs comprising 14 794 patients were included, of whom 7390 (50%) were randomised to colchicine. The mean patient age across the studies ranged from 54 to 63 years, in a follow-up period ranging from 5 days to 12 months. Colchicine reduced the incidence of recurrent ACS (RR 0.41, 95% CI 0.19 to 0.92; p=0.03; I²=55%) and unstable angina (RR 0.27, 95% CI 0.11 to 0.63; p<0.01; I²=0%). No meaningful differences were observed in all-cause mortality (RR 0.95, 95% CI 0.79 to 1.14; I²=12%), cardiovascular death (RR 1.03, 95% CI 0.82 to 1.30; I²=0%) or ACE (RR 0.77, 95% CI 0.59 to 1.01; p=0.05; I²=58%). Subgroup analyses suggested a dose-dependent effect, with 0.5 mg/day potentially reducing ACE (RR 0.63, 95% CI 0.45 to 0.88; I²=41%), but higher doses increasing gastrointestinal symptoms.

Conclusion: Low-dose colchicine may reduce recurrent ischaemic events in ACS, but evidence remains uncertain due to heterogeneity and limited long-term data. Safety and efficacy in women and optimal dosing require further investigation.

Trial registration number: CRD42024627348.

Background: Aortic stenosis (AS) frequently coexists with heart failure (HF), but its prevalence, prognostic impact and management across the full HF spectrum remain incompletely characterised.

Methods: In this retrospective cohort study, we analysed 22 906 patients with HF undergoing echocardiography between 2010 and 2020. AS was classified as mild, moderate, low-gradient (LG) or severe according to guideline criteria. Outcomes were assessed using Cox regression, stratified by HF subtype and adjusted for clinical confounders. The primary endpoint was event-free survival, defined as all-cause mortality or aortic valve replacement (AVR).

Results: Moderate AS was present in 5.5%, LG AS in 2.5% and severe AS in 6.5% of HF patients, with HF with preserved ejection fraction (HFpEF) being the most common HF subtype across all AS grades. Increasing AS severity was associated with a stepwise increase in adverse outcomes compared with HF patients without AS (adjusted HR 2.20 (95% CI 2.00 to 2.41) for moderate AS; 3.32 (95% CI 2.97 to 3.72) for LG AS and 6.20 (95% CI 5.74 to 6.69) for severe AS). These associations were consistent across HFpEF, HF with mildly reduced EF and HF with reduced EF. Despite established guideline indications, only 59.5% (95% CI 57% to 62%) of HF patients with severe AS underwent AVR within 2 years.

Conclusions: AS is common in HF and is associated with substantially worse long-term outcomes across all HF subtypes, even at non-severe stages. The high mortality risk and frequent lack of intervention highlight major treatment gaps and underscore the need for prospective trials evaluating earlier intervention strategies.

Background: Ambient air pollution is associated with heart failure (HF), but underlying biological mechanisms remain unclear. We aimed to elucidate metabolic pathways linking air pollution exposure with HF.

Methods: This prospective cohort study analysed 229 812 UK Biobank participants with nuclear magnetic resonance metabolomics data. Air pollution score was constructed by fine particulate matter, coarse particulate matter, nitrogen dioxide and nitrogen oxides. Air pollution-associated metabolic signatures were identified using elastic net regression among 251 circulating metabolites. Cox regression evaluated associations between metabolic signatures and incident HF risk. Mediation analysis quantified metabolic signatures' role in air pollution-HF relationships.

Results: During median 13.1-year follow-up, 8986 participants (3.9%) developed HF. We identified 53 metabolic metabolites reflecting air pollution exposure, comprising lipoprotein metabolism markers (22.6%), fatty acids (17.0%) and amino acids (13.2%), which were used to construct the air pollution-related metabolic signatures score. After adjustment for confounding factors, each SD increase in the metabolic signatures was associated with 8% elevated HF risk (HR 1.08, 95% CI 1.06 to 1.11). Participants in the highest quantile showed a 24% increased HF risk compared with those in the lowest quantile (HR 1.24, 95% CI 1.16 to 1.3). The metabolic signatures mediated 13.08% (95% CI 12.15% to 15.71%) of air pollution-HF associations, with lipoprotein metabolism and fatty acid signatures as primary mediators.

Conclusions: Air pollution was associated with increased HF risk, with metabolic perturbations appearing to play a mediating role. These metabolic signatures provide insights into potential mechanisms linking air pollution to cardiovascular outcomes.

Mitral annular calcification (MAC) is a progressive, degenerative process increasingly recognised for its clinical impact. Beyond being an incidental finding, MAC contributes to mitral valve dysfunction, arrhythmias, systemic embolisation and elevated cardiovascular risk. In developed countries, it has now overtaken rheumatic disease as the leading cause of mitral stenosis.The pathophysiology of MAC involves chronic mechanical stress, pro-inflammatory activation and osteogenic differentiation of valvular cells. Progression is accelerated by age, chronic kidney disease and metabolic derangements. Diagnosing MAC-related valve dysfunction is challenging, as traditional echocardiographic measures often prove unreliable. Multimodality imaging-including 3D echocardiography and cardiac CT-is essential for assessing anatomy, function and procedural feasibility. Importantly, symptoms often reflect combined valvular (eg, aortic stenosis) and myocardial disease (eg, heart failure with preserved ejection fraction (HFpEF) phenocopy), necessitating careful haemodynamic evaluation to avoid futile interventions.Management should prioritise medical therapy for symptom control and comorbid HFpEF, reserving interventions for selected patients. Surgical and transcatheter approaches carry high risk and should be undertaken only in specialised centres. Future advances may include tailored devices and therapies targeting calcification pathways.