Open Heart最新文献

Introduction: Resistant hypertension remains a clinical challenge, often linked to elevated aldosterone levels not fully controlled by mineralocorticoid receptor antagonists. Aldosterone synthase inhibitors (ASIs) directly suppress aldosterone production. We evaluated the efficacy and safety of ASIs for blood pressure (BP) control.

Method: We performed a Bayesian network meta-analysis of randomised controlled trials (RCTs) assessing systolic (SBP) and diastolic BP (DBP) in adults with hypertension. Major databases were searched to 2025. Treatment effects were summarised as mean differences (MDs) with 95% credible intervals (CrIs), and treatment rankings were determined using the surface under the cumulative ranking curve (SUCRA). Risk of bias was assessed using the Cochrane RoB V.2.0 tool.

Results: Six RCTs including 2149 patients were analysed. Risk of bias assessment using RoB2 showed that four studies were at low risk of bias, and two studies had some concerns. Compared with placebo, Baxdrostat 2 mg once a day significantly reduced SBP (MD -11.0 mm Hg; 95% CrI -21.0 to -0.30), while Osilodrostat 1 mg once a day significantly reduced both SBP (MD -7.6 mm Hg; 95% CrI -14.0 to -0.73) and DBP (MD -5.4 mm Hg; 95% CrI -10.0 to -0.69). Lorundrostat 50 mg once a day also reduced SBP significantly (MD -9.1 mm Hg; 95% CrI -17.0 to -1.7). SUCRA rankings confirmed these findings, with Baxdrostat 2 mg once a day ranking highest for SBP reduction (77%) and Osilodrostat 1 mg two times per day ranking highest for DBP reduction (84%). Most adverse events were mild, serious events were infrequent and no drug-related deaths were reported.

Conclusion: ASIs significantly reduce BP with generally favourable tolerability. Osilodrostat and Baxdrostat demonstrated the most consistent efficacy across outcomes, while Lorundrostat also showed potential benefit. This analysis supports the use of ASIs as effective alternatives for BP reduction. Further large-scale and long-term RCTs are needed to validate these findings and guide clinical decision-making.

Prospero registration number: PROSPERO CRD420251024035.

Background: Atrial fibrillation (AF)-induced cardiomyopathy (AIC) is characterised by reversible left ventricular (LV) dysfunction after restoration of sinus rhythm (SR). The need for continued guideline-directed medical therapy (GDMT) for heart failure after LV ejection fraction (LVEF) recovery in AIC after catheter ablation (CA) is unclear.

Methods: This multicentre cohort study across 12 UK centres included adults undergoing index AF ablation (June 2019-June 2024) with LVEF <50% preablation and recovery to ≥50% at three timepoints: preablation; early postablation (≥4 weeks) and late postablation (≥3 months or ≥3 months post-GDMT withdrawal). Patients were stratified post recovery of LVEF after CA. The primary outcome was mean LVEF at late follow-up; secondary outcomes included absolute change in LVEF, LV end-diastolic diameter (LVEDD) and SR maintenance.

Results: 88 patients met inclusion enrolment criteria (61.7±10.6 years old; 91% male), of which 50 (56.8%) continued full-dose GDMT and 38 (43.2%) withdrew ≥50% of GDMT. In the GDMT-withdrawn group, mean GDMT classes decreased from 2.97±0.88 to 1.03±0.79 (p<0.001). At late follow-up, mean LVEF was comparable (56.3%±3.8% GDMT-continued vs 56.8%±5.5% GDMT-withdrawn; p=0.59), as was LVEF change (1.2% vs 0.4%; p=0.48). One relapse occurred in each group secondary to an acute coronary syndrome (2.0% vs 2.6%; p=1). LVEDD remained stable (p>0.8). SR was maintained in 82.0% vs 92.1% of patients; p=0.17.

Conclusions: Selective GDMT withdrawal after sustained LVEF recovery and rhythm control did not compromise LV systolic function, remodelling or rhythm maintenance. This supports the study of personalised de-escalation strategies in AIC in prospective trials.

Background: Revised haemodynamic criteria for pulmonary hypertension (PH)-mean pulmonary artery pressure (mPAP) >20 mm Hg and pulmonary vascular resistance (PVR) >2 Wood Units (WU)-have defined new subsets of patients with mild PH. We aimed to characterise their clinical profile and prognosis.

Methods: We included consecutive incident, treatment-naïve patients undergoing right heart catheterisation at a PH referral centre. Patients with mPAP 21-24 mm Hg and pulmonary artery wedge pressure (PAWP) ≤15 mm Hg were stratified by PVR values to identify those with unclassified PH (PVR≤2 WU) and mild precapillary PH (PVR>2 WU). Patients with mild precapillary PH were compared with matched controls with normal haemodynamics and with patients meeting previous pulmonary arterial hypertension (PAH) haemodynamic criteria (mPAP≥25 mm Hg, PAWP≤15 mm Hg, PVR>3 WU).

Results: Among 259 patients with mPAP 21-24 mm Hg and PAWP≤15 mm Hg, 76% had left heart or lung disease. In unclassified PH, mPAP elevation was mainly due to high stroke volume index (SVI) or backward transmission from borderline PAWP. In mild precapillary PH, SVI was the only independent haemodynamic predictor of survival. Survival was similar between mild precapillary PH and PAH patients. A limited number of patients with PAH risk factors progressed to overt PAH and, in the absence of comorbidities, appeared to benefit from PAH therapies.

Conclusions: Unclassified PH is mainly related to pulmonary overflow or backward transmission from borderline PAWP. Mild precapillary PH is typically associated with comorbidities and not necessarily an early PAH stage. SVI is a key prognostic marker. Careful clinical phenotyping is essential to identify the small subset who may benefit from targeted therapies.

Objective: To clarify whether atherogenic index of plasma (AIP), a comprehensive indicator reflecting both the protective and atherogenic effects of lipoproteins on cardiometabolic health, is associated with increased risk of aortic disease.

Design: Large-scale, population-based, observational, prospective cohort study.

Data sources: Health dataset from UK Biobank.

Participants: A total of 17 530 participants, aged 40-70 years, were enrolled and completed the initial assessment visit before 2010. Participants with a history of aortic dissection (AD) or aortic aneurysm (AA), baseline connective tissue disease, missing triglyceride and high-density lipoprotein cholesterol values, fasting time less than 8 hours or those lost to follow-up were excluded.

Main outcome measures: Aortic disease, a composite outcome comprising AD and AA.

Results: During a median follow-up period of 15.1 years, 164 aortic disease cases, including 14 AD and 155 AA cases, were documented. A linear trend between AIP and the risk of incident aortic disease was confirmed (p for non-linear=0.134). The multivariable-adjusted incident risk of aortic disease gradually increased with elevated AIP tertiles (adjusted HR (aHR) 1.0 (reference) in tertile 1, aHR 1.48 (95% CI 0.91 to 2.41) in tertile 2, aHR 2.04 (95% CI 1.26 to 3.29) in tertile 3), following an adjustment for age, sex, smoking status, drinking status, body mass index, hypertension, low-density lipoprotein cholesterol and glycated haemoglobin. Specifically, participants in the highest AIP tertile had the highest incident risk of AA, with an aHR of 2.47 (95% CI 1.47 to 4.16).

Conclusions: AIP is significantly associated with a higher risk of incident aortic disease, indicating that AIP is an effective risk assessment method for aortic disease, especially for AA.

Background: Circulating proprotein convertase subtilisin/kexin type 9 (PCSK9) is a crucial regulator of cholesterol metabolism. Loss-of-function variants in PCSK9 are associated with lower levels of circulating low-density lipoprotein cholesterol (LDL-C) and reduced cardiovascular disease (CVD) risk, while gain-of-function variants correlate with elevated LDL-C concentrations and increased CVD risk. This study investigated whether genetically determined LDL-C levels, proxied by four PCSK9 genetic variants, influence common carotid artery atherosclerosis.

Methods: The analysis included 3040 European participants (mean age 64.2±5.4 years; 45.8% men) at high cardiovascular risk from the IMPROVE Study, alongside 49 088 individuals of white British ancestry (mean age 55.2±7.6 years; 47.9% men) from the UK Biobank (UKB). Ultrasonographic measurements of common carotid intima-media thickness (CC-IMTmean, CC-IMTmax, CC-IMTmean-max) were obtained. Four lipid-level affecting genetic variants in the PCSK9 locus were selected for analysis, both individually and in a standardised Lipid-Lowering Allelic Score (LLAS), to assess their effects on LDL-C and PCSK9 levels in the IMPROVE cohort and on ultrasonographic measures in both IMPROVE and UKB.

Results: In the IMPROVE cohort, PCSK9 variants (rs11206510, rs2479409, rs11591147, rs11583680) exhibited expected effect directions, although not all statistically significant, on LDL-C and PCSK9 levels. The LLAS was negatively correlated with CC-IMTmean, CC-IMTmax and CC-IMTmean-max among women in IMPROVE, and among men and overall in UKB (all p<0.05). Effect sizes were comparable between cohorts.

Conclusions: Genetic variants in the PCSK9 locus influence LDL-C levels and CC-IMT, in keeping with proven benefits of PCSK9 inhibitors on atherosclerotic cardiovascular events.

Background: Aortogenic stroke is an important subtype of embolic strokes, yet lacks a diagnostic method for proactive identification. Non-obstructive general angioscopy (NOGA) is a catheter-based technique to observe spontaneously ruptured aortic plaques (SRAPs), a potential embolic source of ischaemic stroke.

Objectives: This study aimed to identify the embolic source of ischaemic stroke using NOGA.

Methods: From June 2022 to January 2024, 321 consecutive patients with acute ischaemic stroke were hospitalised. 25 underwent emergent mechanical thrombectomy and NOGA. The aortic arch was screened using NOGA, and atherosclerotic materials from the SRAPs were sampled and pathologically analysed. Transoesophageal echocardiography (TEE) was performed the day after catheterisation to investigate intracardiac thrombus, patent foramen ovale and aortic plaques. The primary outcome was the diagnosis of aortogenic stroke.

Results: NOGA identified seven SRAPs in the aortic arch as potential embolic sources. Of those, one patient with atrial fibrillation and cardiac chamber thrombus was diagnosed as having a cardiogenic stroke. The findings of the six remaining cases included aortic arch plaque (also observed via TEE) (n=2), thrombus in an artificial aortic graft wall (n=1), and cholesterol crystals in sampled materials indicating plaque rupture (n=3). The Brain-Heart team finally diagnosed these 6 cases (24%) as aortogenic stroke. 16 patients were diagnosed with cardiogenic stroke. One was diagnosed with paradoxical embolism. The remaining two cases (8%) with unidentified embolic sources were diagnosed with cryptogenic stroke.

Conclusions: Using a systematic diagnostic protocol for embolic source detection, the Brain-Heart team could proactively diagnose aortogenic stroke and clarify embolic source.

Background: Aortic stenosis (AS) and coronary artery disease (CAD) frequently coexist, requiring careful revascularisation strategy consideration. While surgical aortic valve replacement (SAVR) plus coronary artery bypass grafting (CABG) is traditional, transcatheter aortic valve replacement (TAVR) plus percutaneous coronary intervention (PCI) is increasingly used. The optimal strategy, particularly regarding residual CAD burden, remains unclear.

Objectives: This study investigated the impact of residual SYNTAX (Synergy between Percutaneous Coronary Intervention with Taxus and Cardiac Surgery) score (rSS) on outcomes in men and women with AS and CAD undergoing TAVR+PCI versus SAVR+CABG.

Methods: In this retrospective study, propensity score-matched cohorts of men and women undergoing either procedure were analysed. Matching variables included age, left ventricular ejection fraction, EuroSCORE II (European System for Cardiac Operative Risk Evaluation II) and CAD severity.

Results: 398 patients (114 women and 284 men) were included. The rSS was predictive of the primary composite endpoint in the TAVR+PCI group (p=0.006 women and p<0.001 men) but not in the SAVR+CABG group. In patients achieving an rSS<8, TAVR+PCI was associated with a lower combined endpoint rate compared with SAVR+CABG, consistent across genders (p=0.02). Furthermore, TAVR+PCI demonstrated significant safety benefits, including lower rates of major bleeding in men (2.1% vs 10.6%) and stroke in women (1.8% vs 12.3%).

Conclusions: The prognostic importance of the rSS is strategy-dependent. For patients undergoing TAVR+PCI, achieving extensive revascularisation (rSS <8) is a critical procedural goal associated with improved outcomes. For patients undergoing SAVR+CABG, prognosis appears driven more by baseline clinical risk.

Purpose: Sotatercept, an activin signalling inhibitor approved in March 2024 for pulmonary arterial hypertension (PAH), demonstrated efficacy in clinical trials. This pharmacovigilance study evaluated its real-world safety profile using the US Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) to identify postmarketing risks.

Methods: FAERS reports from 2024 were analysed, focusing on cases where sotatercept was designated as the primary suspect. Duplicate entries were removed using standardised FDA protocols. Adverse events (AEs) were categorised using the Medical Dictionary for Regulatory Activities (MedDRA V.28.0). Disproportionality signals were assessed via reporting ORs (RORs; 95% CI lower limit >1 with ≥3 cases). Severity was classified using the EudraVigilance Important Medical Events (IMEs) list.

Results: Among 1 484 350 deduplicated reports, 613 sotatercept-associated AEs (1717 occurrences, 395 MedDRA terms) were identified. Disproportionality analysis revealed 48 safety signals: 30 aligned with labelled risks (eg, haemoglobin elevation (ROR=272.2), telangiectasia (ROR=334.1)) and 18 novel signals. The most frequent AEs included headache (n=78), epistaxis (n=57) and diarrhoea (n=53). Two unlabelled events-cerebral haemorrhage and ascites-met criteria for critical IMEs. Most reports originated from the USA (98.5%) and involved females (73.6%).

Conclusion: This study confirms sotatercept's labelled risks (haematological and vascular effects) and identifies novel safety concerns, including cerebral haemorrhage and ascites, highlighting the need for vigilant monitoring in PAH management. Real-world data underscore the value of postmarketing surveillance for detecting rare or unanticipated AEs. Clinicians should prioritise monitoring for haematological abnormalities and bleeding risks. Longitudinal studies are warranted to clarify long-term safety outcomes.

Background: Routine invasive management by coronary angiography and revascularisation as appropriate reduces recurrent ischaemic events in non-ST-segment myocardial infarction (NSTEMI), but its mortality benefit is uncertain.

Methods: Within this state-wide retrospective cohort study, patients with a primary diagnosis of NSTEMI were identified from the New South Wales (NSW) Admitted Patient Data Collection database between 2003 and 2020 and linked to the NSW death registry. Primary outcomes were cardiovascular (CV) and all-cause mortality among NSTEMI patients stratified by in-hospital invasive management.

Results: Among 121 089 patients with NSTEMI (median age 71.4 years; 62.7% men), invasive management increased from 48.8% to 66.8% while all-cause in-hospital mortality decreased from 4.8% to 2.9% between triennial periods of 2003-2005 and 2018-2020, respectively. During the follow-up period (median 8.47 years), 47 304 (39.1%) patients died. CV mortality fell between 2003 and 2020 for those who were and were not invasively managed with greater magnitude in the former (subdistribution HR (sHR)=0.32, 95% CI 0.29 to 0.36; sHR=0.58, 95% CI 0.54 to 0.63, respectively, p_interaction<0.001). For all-cause mortality, the fall was significant for the invasively managed patients, with no plateau evident, but not in patients managed conservatively (adjusted HR (aHR)=0.56, 95% CI 0.52 to 0.61; aHR=1.00, 95% CI 0.95 to 1.06, respectively, p_interaction<0.001).

Conclusions: In patients presenting to NSW hospitals with NSTEMI between 2003 and 2020, we observed improvements in CV mortality in both invasively and conservatively managed patients while all-cause mortality improved in invasively but not conservatively managed patients. Wider implementation of routine invasive management may further improve long-term mortality among NSTEMI patients in NSW.

Background: Biochemical markers of inflammation, coagulation and myocardial stress have been associated with both prevalent and incident atrial fibrillation (AF), but little is known about the relationship between biomarker expression and AF burden.

Aims: Our aim was to investigate the association between cardiovascular biomarkers and AF burden and AF episode duration ≥24 hours.

Methods and results: In this multicentre observational cohort study, we included 404 patients with paroxysmal AF from the Reappraisal of Atrial Fibrillation: Interaction between Hypercoagulability, Electrical Remodelling and Vascular Destabilisation in the Progression of AF study and evaluated a total of 92 potential cardiovascular blood biomarkers. All patients completed 1 year of follow-up with continuous rhythm monitoring using an implanted loop recorder or a dual-chamber pacemaker. The relationship between biomarker expression and AF was investigated using multiple regression including nine preselected covariates: age, sex, prior heart failure, hypertension, renal insufficiency, prior stroke, coronary artery disease, body mass index and treatment with antiarrhythmic drugs. Elevated levels of N-terminal pro-B-type natriuretic peptide (NT-proBNP) were associated with higher AF burden (incidence rate ratio 1.75, 95% CI 1.75 to 2.06) and AF episode duration ≥24 hours (OR 1.78, 95% CI 1.39 to 2.27). Increased levels of matrix metalloproteinase 2, neurogenic locus notch homologue protein 3 and tumour necrosis factor receptor 2 were additionally associated with AF episode durations ≥24 hours.

Conclusions: Higher circulating levels of NT-proBNP are associated with increased AF burden and AF episode duration ≥24 hours in patients with paroxysmal AF.

Trial registration number: NCT02726698.