Background Echocardiographic grading of mitral regurgitation (MR) relies on the American Society of Echocardiography (ASE) multiparametric algorithm, with limitations in reproducibility and feasibility. Average pixel intensity (API) from continuous-wave Doppler (CWD) has been proposed as a geometry-independent complement but lacks external validation.Methods Prospective single-centre study of 372 patients with at least mild MR. API was measured offline from CWD images using open-source software. Diagnostic performance was assessed against ASE grading and cardiac magnetic resonance (n=93). Survival analysis used Kaplan-Meier and Cox regression, separately for secondary MR (SMR) and primary MR (PMR). API reproducibility was evaluated using test-retest, inter-reader and beat-to-beat analyses.Results API was feasible in 96% versus 77% for effective regurgitant orifice area (EROA). Although API-EROA correlation was weak (R=0.32), API showed good discrimination of MR grades III–IV in SMR and central jets (area under the curve (AUC) 0.85 in both), moderate in PMR (AUC 0.73) and poor in eccentric jets (AUC 0.61). Against cardiac magnetic resonance, EROA showed higher overall accuracy than API (AUC 0.81 vs 0.67), but API outperformed EROA in central jets. During a median follow-up of 14.3 months (IQR 9–36), 33.8% experienced the composite endpoint (mitral intervention, heart failure hospitalisation, transplantation or death). Among patients with ASE grades I–II, API>150 in SMR and >112 in PMR identified a subgroup with event rates comparable to grades III–IV. API independently predicted outcomes in SMR (HR 1.9, 95% CI 1.1 to 3.1, p=0.015) and PMR (HR 3.2, 95% CI 1.1 to 9.7, p=0.039), with incremental prognostic value over ASE grading in SMR (ΔC-statistic 0.086, p<0.001). Principal variability sources were acquisition-related (coefficient of variation (CV) 10.4%) and beat-to-beat variation in atrial fibrillation (CV 9.9%).Conclusions API quantification was highly feasible and provides complementary diagnostic and prognostic information. In mild-to-moderate MR, particularly SMR, high API identifies individuals at elevated event risk, supporting its potential role for risk stratification.
Aim To assess adherence to statin therapy in women and men in Dutch routine care data.Methods Data on statin dispensing was extracted from the PHARMO Data Network in the Netherlands between 2011 and 2020. We assessed primary non-adherence, non-compliance and discontinuation of statin therapy in a population-based cohort of new statin users aged >40 years and assessed sex differences. We evaluated the association of non-compliance with cardiovascular hospitalisations and mortality with Cox proportional hazard models weighted with inverse probability weights.Results We identified 68 707 new users of statin therapy (46% women) with a median age of 65 years (Q1–Q3: 57–72). In total, 9% of women and 8% of men were primary non-adherent, with women being 8% (95% CI 4 to 12) more likely to be primary non-adherent in the first year after initiating statins compared with men. The mean proportion of days covered in this first year after initiation was 81% for women and 83% for men; the adjusted women-to-men risk ratio for non-compliance was 1.06 (95% CI 1.03 to 1.08). The cumulative incidence of discontinuation at 1 year was 23% in women and 20% in men, with women being 13% (95% CI 10 to 15) more likely to discontinue statin therapy compared with men. Non-compliance to statin therapy was associated with a 17% higher risk of cardiovascular hospitalisations and mortality in women (95% CI 10 to 23) and 14% higher risk in men (95% CI 8 to 20) (ratio of HRs: 1.02 (95% 0.95 to 1.11)).Conclusion Women were less likely than men to be adherent to statin therapy, though the differences were marginal in absolute terms. Non-adherence was associated with a higher risk of cardiovascular hospitalisations and mortality.
Background High-sensitivity cardiac troponin (hs-cTn) is central to the early assessment of patients presenting with acute chest pain and suspected non-ST-elevation acute coronary syndrome (NSTE-ACS) while clinical risk scores remain widely used for risk stratification. Whether established scores provide incremental information beyond admission hs-cTn in contemporary high-risk populations remains uncertain. We evaluated the incremental discriminative value of HEAR and GRACE 2.0 beyond admission high-sensitivity cardiac troponin I (hs-cTnI).Methods In this prospective single-centre cohort, 995 patients presenting with acute chest pain were screened between March and November 2024. After predefined exclusions and follow-up assessment, 681 patients with suspected NSTE-ACS were included. The primary endpoint was 30-day myocardial infarction (MI) or all-cause death. Incremental diagnostic and risk-stratification value was assessed using multivariable logistic regression and receiver-operating characteristic analyses.Results Among 681 patients, mean age was 64.2 years, 63% were male and 63.5% had established coronary artery disease. At 30 days, 182 patients experienced MI and 12 died. In multivariable analysis, each doubling of admission hs-cTnI was independently associated with the primary endpoint (adjusted OR 2.03, 95% CI 1.77 to 2.38; p<0.001), whereas neither HEAR (adjusted OR 0.98, 95% CI 0.76 to 1.26; p=0.868) nor GRACE 2.0 (adjusted OR 0.99, 95% CI 0.97 to 1.01; p=0.280) provided incremental information beyond hs-cTnI. Admission hs-cTnI showed strong discrimination for MI or death (area under the curve 0.918), and adding either HEAR or GRACE 2.0 did not improve discriminative performance.Conclusions In this tertiary-care cohort of patients with suspected NSTE-ACS and a high prevalence of established coronary artery disease, HEAR and GRACE 2.0 provided limited incremental discriminatory value beyond admission hs-cTnI for MI or all-cause death within 30 days.
Objectives This study aims to understand the natural history of early-stage hypertrophic cardiomyopathy (HCM) patients and identify risk factors for disease progression.Background HCM is a phenotypically heterogeneous disease, characterised by a wide range of clinical outcomes, from asymptomatic to severe heart failure.Methods The predictorS Of cLinical outcomEs iN hypertrOphIc carDiomyopathy (SOLENOID) is an observational, multicentre cohort study conducted across five centres in Europe and the USA. Inclusion criteria were patients with confirmed HCM seen between 2010 and 2022 in New York Heart Association (NYHA) class I. The study’s endpoint was a composite of worsening NYHA class (=N+1) and unplanned cardiovascular hospitalisation, assessed using Kaplan-Meier analysis. Risk factors were identified through univariate analyses at each centre, with results aggregated through meta-analysis.Results A total of 961 patients were included, with a median follow-up of 4 years. The mean age was 54±16 years and 29% of the cohort were females. 43% of patients were treated with beta-blockers and 13% had pre-existent atrial fibrillation (AF). Genetic testing revealed mutations primarily in MYBPC3 (30%) and MYH7 (13%) genes.Incidence of the composite endpoint was 26% and 41% at 3 and 5 years, respectively, with NYHA class worsening as the main contributor. The main predictors of the composite endpoint include older age (log-HR=0.33, p<0.05), chronic obstructive pulmonary disease (log-HR=1.18, p<0.001), chest pain (log-HR=0.60, p<0.05), fatigue (log-HR=0.73, p<0.01), AF on electrocardiography (log-HR=1.56, p<0.0001), higher N-terminal pro B-type natriuretic peptide levels (log-HR=0.75, p<0.0001), larger left atrial volume index (log-HR=0.29, p=0.04), peak A-wave velocity (log-HR=0.38, p=0.04) and maximal end-diastolic left ventricle wall thickness (log-HR=0.36, p=0.04).Conclusion Nearly 30% of the early-stage HCM patients experienced disease progression over 3 years, highlighting a medical unmet need. Further research is needed to determine if this population might benefit from intensive monitoring or earlier therapy.
Background Intravenous iron may improve symptoms and reduce heart-failure hospitalisation, but its effect on infection risk remains uncertain. We evaluated infection risk and clinical outcomes in adults with heart failure and iron deficiency.Methods We searched MEDLINE, Embase and Scopus from inception to 16 April 2026, with registry and regulatory searches through 18 October 2026. Randomised controlled trials comparing intravenous iron with placebo, usual care or oral iron were eligible. Participants experiencing infection and infection episodes were analysed separately using random-effects binomial-normal and Poisson-normal models, respectively. Common-effect models were prioritised for mortality and hospitalisation, with random-effects sensitivity analyses. Risk of bias and certainty were assessed using Risk of Bias 2 and Grading of Recommendations Assessment, Development and Evaluation.Results Nineteen reports represented 18 independent cohorts. Three trials contributed participant-level data for any infection (1873 participants; OR 0.82, 95% CI 0.64 to 1.08; low certainty), and three contributed data for serious infection (1890 participants; OR 0.83, 95% CI 0.51 to 1.21; very low certainty). Infection-episode analyses were inconclusive: episode-burden ratios were 1.07 (95% CI 0.76 to 1.86; four trials) for any infection and 1.11 (0.82 to 1.42; seven trials) for serious infection, both with very low GRADE certainty. Intravenous iron probably reduced total first and recurrent heart-failure hospitalisations (three trials; rate ratio 0.78, 95% CI 0.67 to 0.90; moderate certainty). Intravenous iron probably has little or no effect on all-cause mortality (six trials; HR 0.93, 95% CI 0.84 to 1.03; moderate certainty). Quality-of-life findings generally favoured intravenous iron, but differences in instruments, score types and assessment times precluded pooling.Conclusions Intravenous iron probably reduces heart-failure related hospitalisations. No clear increase in infection was observed. Incomplete reporting, inconsistent ascertainment and sparse data limit inference about infection safety. Future trials should prespecify standardised infection outcomes, and report affected participants, recurrent events and person-time.PROSPERO registration number CRD420261355349.
