Socio-economic inequalities and heart failure morbidity and mortality: A systematic review and data synthesis.

Socio-economic status (SES) has been associated with incident and prevalent heart failure (HF), as well as its morbidity and mortality. However, the precise nature of the relationship between SES and HF remains unclear due to inconsistent data. This study aims to provide a comprehensive assessment and data synthesis of the relationship between SES and HF morbidity and mortality. We performed a systematic search and data synthesis using six databases following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Guidelines. The included studies comprised observational studies that reported on HF incidence and prevalence, HF hospitalizations, worsening HF (WHF) and all-cause mortality, as well as treatment options (medical, device and advanced HF therapies). SES was measured on both individual and area levels, encompassing single (e.g., income, education, employment, social risk score, living conditions and housing characteristics) and composite indicators. Among the 4124 studies screened, 79 were included, with an additional 5 identified through cross-referencing. In the majority of studies, a low SES was associated with an increased HF incidence (72%) and prevalence (75%). For mortality, we demonstrated that low SES was associated with increased mortality in 45% of the studies, with 18% of the studies showing mixed results (depending on the indicator, gender or follow-up) and 38% showing non-significant results. Similar patterns were observed for the association between SES, WHF, medical therapy prescriptions and the utilization of devices and advanced HF therapies. There was no clear pattern in the used SES indicators and HF outcomes. This systematic review, using contemporary data, shows that while socio-economic disparity may influence HF incidence, management and subsequent adverse events, these associations are not uniformly predictive. Our review highlights that the impact of SES varies depending on the specific indicators used, reflecting the complexity of its influence on health disparities. Assessment and recognition of SES as an important risk factor can assist clinicians in early detection and customizing HF treatment, while also aiding policymakers in optimizing resource allocation.

Impact of Stenting Long Lesions on Clinical Outcomes in Patients Presenting With Acute Coronary Syndrome and Multivessel Disease: Data From the BIOVASC Trial.

An increased total stent length (TSL) might be associated with a higher risk of clinical events; however, in patients with multivessel disease (MVD), a considerable TSL is often required. In patients presenting with acute coronary syndrome and MVD, immediate complete revascularization was associated with shorter TSL in the BIOVASC Trial. This is a subanalysis of the BIOVASC trial comparing clinical outcomes in patients with either <60 or ≥60 mm TSL. The primary outcome was a composite of all-cause mortality, myocardial infarction, any unplanned ischemia driven revascularization, or cerebrovascular events at 2 years after the index procedure. A total of 1,525 patients were enrolled in the BIOVASC trial, of whom 855 had a TSL of ≥60 mm (long TSL). No significant difference was established when comparing patients treated with either long or short TSL in terms of the primary outcome at 2-year follow-up, which occurred in 117 patients (13.7%) in the ≥60 mm group and 69 patients (10.3%) in the <60 mm group (adjusted hazard ratio 1.25, 95% confidence interval 0.92 to 1.69, p = 0.16). Furthermore, no significant differences were observed in the secondary end points. In conclusion, in patients with acute coronary syndrome and MVD, long stenting did not show a significant difference in clinical event rate compared with short stenting.

Age-specific sex differences in intravascular ultrasound based coronary atherosclerotic plaque characteristics.

Insights in age- and sex-specific coronary atherosclerotic plaque characteristics may contribute to a better understanding of coronary artery disease and, ultimately, to its prevention and treatment. In 307 women and 406 men aged 20 to 90 years undergoing intravascular ultrasound imaging, sex-based differences in coronary atherosclerotic plaque characteristics were mainly present in younger patients, while these differences were less pronounced at advanced age.

Blood Biomarkers Predict 10-Year Clinical Outcomes in Adult Patients With Congenital Heart Disease.

Background: The adult congenital heart disease (ACHD) population is growing and risk prediction is important to predict adverse outcome and consult patients during their lifecourse. Objectives: This study aims to describe the long-term prognostic value of blood biomarkers in ACHD. Methods: In this prospective observational cohort study, 602 patients with moderate or complex ACHD were included (median age 32.5 years [IQR: 24.7-41.2], 42% female, 90% New York Heart Association I). N-terminal pro-brain natriuretic peptide (NT-proBNP), high-sensitive-troponin T, growth differentiation factor 15, high-sensitive-C-reactive protein, suppression of tumorigenicity-2 and galectin-3, as well as full blood count, renal function, LDL, and HDL were measured. Cox models were applied to relate the selected biomarkers with the primary end point of all-cause mortality and secondary end point of mortality or heart failure. Standardized HRs adjusted for relevant prognostic factors, including age, sex, and complexity of diagnosis, were reported. Results: Abnormal biomarker levels were present in 424 (70.4%) patients. During a median follow-up of 10.1 years, 41 (6.8%) patients died and 81 (13.5%) developed heart failure. Associations were observed between the primary and secondary end point and red cell distribution width, NT-proBNP, and growth differentiation factor 15. In a multibiomarker model, only NT-proBNP remained associated with mortality (HR: 2.74; 95% CI: 2.01-3.74). NT-proBNP significantly improved the C-statistic of the clinical prediction model (0.85-0.92). Based on NT-proBNP alone, low-risk patients could be identified. Patients with NT-proBNP <76 ng/L showed a 10-year heart failure-free survival of 98.5%. Conclusions: Blood biomarkers have prognostic value in ACHD. NT-proBNP improves risk prediction and is able to identify low-risk patients. Its routine use should be implemented in ACHD.

Burden of risk factors in women and men with unrecognised myocardial infarction: a systematic review and meta-analysis.

AIMS: Unrecognised myocardial infarction (MI) is a MI that remains undetected in the acute phase and is associated with an unfavourable prognosis. With this systematic review and meta-analysis, we evaluated the burden of cardiovascular risk factors in individuals with unrecognised MI. METHODS AND RESULTS: We searched general population-based cohort studies diagnosing unrecognised MI by electrocardiogram or myocardial imaging up to 24 November 2023. Pooled mean differences (MD) or risk ratios (RR) with 95% confidence intervals (CI) were determined, and random-effects meta-analyses were performed. Fourteen cohort studies were included involving 200,450 individuals (mean age 62.8±9.9 years, 56.0% women), among which 4,322 (2.2%) experienced unrecognised MI (mean age 66.3±8.2 years, 47.8% women) and 4,653 (2.1%) recognised MI (mean age 68.5±7.3 years, 33.8% women). Compared to individuals without MI, those with unrecognised MI had higher body mass index (MD 0.27, 95% CI 0.16-0.39) and systolic blood pressure (MD 4.48, 95% CI 2.81-6.15), and higher prevalence of hypertension (RR 1.27, 95% CI 1.06-1.51) and diabetes mellitus (RR 1.67, 95% CI 1.36-2.06). Furthermore, individuals with unrecognised MI had lower prevalence of hypertension (RR 0.92, 95% CI 0.88-0.97) and diabetes mellitus (RR 0.80, 95% CI 0.70-0.92). CONCLUSION: Individuals with unrecognised MI are characterised by a substantial burden of metabolic risk factors. Our findings suggest insufficient recognition and management of cardiovascular risk factors among individuals with unrecognised MI.

Association of baseline and longitudinal changes in insulin-like growth factor-binding protein-7 with the risk of incident heart failure: Data from the PREVEND study.

AIM: Senescence is a major risk factor for heart failure (HF), and insulin-like growth factor-binding protein-7 (IGFBP7) has been identified as an important senescence-inducing factor. The aim of this study was to examine the value of baseline and repeat IGFBP7 measurements in predicting future HF among community-dwelling Dutch adults from the Prevention of Renal and Vascular End-stage Disease (PREVEND) study. METHODS AND RESULTS: Individuals without prevalent HF who attended PREVEND visits 2 and 4 median of 5.1 years apart (25th-75th percentile, 4.9-5.2) with measurements of IGFBP7 were included. We used Cox proportional hazards models to investigate the association between IGFBP7 and HF incidence. A total of 6125 participants attending visit 2 (mean ± standard deviation [SD] age 53.1 ± 12.2 years; 3151 [51.4%] men) were followed for a median of 8.4 (7.8-8.9) years, and 194 participants (3.2%) developed incident HF. Median baseline IGFBP7 concentration was 87.0 (75.1-97.3) ng/ml, and baseline IGFBP7 levels were significantly associated with risk for incident HF (HF risk factors adjusted hazard ratio [HR] per 1 SD change in log-transformed IGFBP7: 1.22, 95% confidence interval [CI] 1.03-1.46). Baseline IGFBP7 was also significantly associated with incident HF in individuals with N-terminal pro-B-type natriuretic peptide <125 ng/L. Among 3879 participants attending both visits 2 and 4 (mean ± SD age 57.5 ± 11.3 years; 1952 [50.3%] men), 93 individuals developed HF (after visit 4) during a median follow-up of 3.2 (2.8-3.9) years. Median increase in IGFBP7 concentration between visits was 0.68 (-7.09 to 8.36) ng/ml, and changes in IGFBP7 levels were significantly associated with risk for incident HF (HF risk factors adjusted HR per 1 SD change in log-transformed IGFBP7: 1.68, 95% CI 1.19-2.36). CONCLUSIONS: Both baseline as well as repeat IGFBP7 measurements provide information about the risk of developing HF.

Proteomic biomarkers related to obesity in heart failure with reduced ejection fraction and their associations with outcome.

OBJECTIVE: Heart failure (HF) pathophysiology in patients with obesity may be distinct. To study these features, we identified obesity-related biomarkers from 4210 circulating proteins in patients with HF with reduced ejection fraction (HFrEF) and examined associations of these proteins with HF prognosis and biological mechanisms. METHODS: In 373 patients with trimonthly blood sampling during a median follow-up of 2.1 (25th-75th percentile: 1.1-2.6) years, we applied an aptamer-based multiplex approach measuring 4210 proteins in baseline samples and the last two samples before study end. Associations between obesity (BMI > 30 kg/m2) and baseline protein levels were analyzed. Subsequently, associations of serially measured obesity-related proteins with biological mechanisms and the primary endpoint (PEP; composite of cardiovascular mortality, HF hospitalization, left ventricular assist device implantation, and heart transplantation) were examined. RESULTS: Obesity was identified in 26% (96/373) of patients. A total of 30% (112/373) experienced a PEP (with obesity: 26% [25/96] vs. without obesity: 31% [87/277]). A total of 141/4210 proteins were linked to obesity, reflecting mechanisms of neuron projection development, cell adhesion, and muscle cell migration. A total of 50/141 proteins were associated with the PEP, of which 12 proteins related to atherosclerosis or hypertrophy provided prognostic information beyond clinical characteristics, N-terminal pro-B-type natriuretic peptide, and high-sensitivity troponin T. CONCLUSIONS: Patients with HFrEF and obesity show distinct proteomic profiles compared to patients with HFrEF without obesity. Obesity-related proteins are independently associated with HF outcome. These proteins carry potential to improve management of obesity-related HF and could be leads for future research.

Immediate versus staged complete revascularisation in patients presenting with STEMI and multivessel disease.

BACKGROUND: Complete revascularisation is supported by recent trials in patients with ST-elevation myocardial infarction (STEMI) and multivessel disease (MVD) without cardiogenic shock. However, the optimal timing of non-culprit lesion revascularisation is currently debated. AIMS: This prespecified analysis of the BioVasc trial aims to determine the effect of immediate complete revascularisation (ICR) compared to staged complete revascularisation (SCR) on clinical outcomes in patients with STEMI. METHODS: Patients presenting with STEMI and MVD were randomly assigned to ICR or SCR. The primary endpoint was the composite of all-cause mortality, myocardial infarction, any unplanned ischaemia-driven revascularisation, or cerebrovascular events at 1-year post-index procedure. RESULTS: Between June 2018 and October 2021, 608 (ICR: 305, SCR: 303) STEMI patients were enrolled. No significant differences between ICR and SCR were observed at 1-year follow-up in terms of the primary endpoint (7.0% vs 8.3%, hazard ratio [HR] 0.84, 95% confidence interval [CI]: 0.47-1.50; p=0.55): all-cause mortality (2.3% vs 1.3%, HR 1.77, 95% CI: 0.52-6.04; p=0.36), myocardial infarction (1.7% vs 3.3%, HR 0.50, 95% CI: 0.17-1.47; p=0.21), unplanned ischaemia-driven revascularisation (4.1% vs 5.0%, HR 0.80, 95% CI: 0.38-1.71; p=0.57) and cerebrovascular events (1.4% vs 1.3%, HR 1.01, 95% CI: 0.25-4.03; p=0.99). At 30-day follow-up, a trend towards a reduction of the primary endpoint in the ICR group was observed (ICR: 3.0% vs SCR: 6.0%, HR 0.50, 95% CI: 0.22-1.11; p=0.09). ICR was associated with a reduction in overall hospital stay (ICR: median 3 [interquartile range {IQR} 2-5] days vs SCR: median 4 [IQR 3-6] days; p<0.001). CONCLUSIONS: Clinical outcomes at 1 year were similar for STEMI patients who had undergone ICR and those who had undergone SCR.

Trends in population attributable fraction of modifiable risk factors for cardiovascular diseases across three decades.

AIM: To evaluate temporal trends, across three decades, in the population attributable fractions (PAFs) of modifiable risk factors for 5-year risk of cardiovascular diseases (CVDs). METHODS: Within population-based Rotterdam Study, we defined three time-groups of individuals without established CVD at 'baseline' with a mean age of 70 years, and followed for five years: Epoch 1990s (1989-1993, N=6195), Epoch 2000s (1997-2001, N=5572) and Epoch 2010s (2009-2014, N=5135). The prevalence of risk factors and related relative risks were combined to quantify PAFs. RESULTS: The PAF of the six risk factors combined for global CVD was 0.57 (95% confidence interval [CI] 0.47 to 0.65), 0.52 (0.39 to 0.62) and 0.39 (0.18 to 0.54) in three respective epochs. Hypertension contributed the highest PAF to global CVD in Epoch 1990s (0.37, 95% CI: 0.28 to 0.44) and 2000s (0.34, 95% CI: 0.22 to 0.43), while smoking was the largest contributor in Epoch 2010s (0.20, 95% CI: 0.06 to 0.32). Dyslipidemia changed population-level coronary heart disease risk over time. For stroke, hypertension became a less significant contributor over time, but smoking became a larger contributor. For heart failure, all risk factors showed non-significant PAFs in Epoch 2010s. PAFs related to individual risk factor varied among women and men. CONCLUSION: Six modifiable risk factors to population-level global CVD risk decreased over time, but still explained 39% of total CVD in the latest decade. PAFs changed considerably for hypertension, dyslipidemia, and smoking. Risk factors had different PAFs for different CVDs with pronounced sex differences.

The contribution of the individual cardiovascular risk factors to population CVD risk considerably changed over the past 3 decades, especially for hypertension, dyslipidemia, and smoking. Traditional modifiable risk factors exerted declining contributions to population burden of total CVD over the past three decades, suggesting good progress in CVD prevention. Nonetheless, in the latest decade, unfavorable risk factors accounted for 39% of total CVD burden. Sex differences in the contributions of abdominal obesity, diabetes and smoking to cardiovascular outcomes were observed.

Identifying plasma proteomic signatures from health to heart failure, across the ejection fraction spectrum.

Circulating proteins may provide insights into the varying biological mechanisms involved in heart failure (HF) with preserved ejection fraction (HFpEF) and reduced ejection fraction (HFrEF). We aimed to identify specific proteomic patterns for HF, by comparing proteomic profiles across the ejection fraction spectrum. We investigated 4210 circulating proteins in 739 patients with normal (Stage A/Healthy) or elevated (Stage B) filling pressures, HFpEF, or ischemic HFrEF (iHFrEF). We found 2122 differentially expressed proteins between iHFrEF-Stage A/Healthy, 1462 between iHFrEF-HFpEF and 52 between HFpEF-Stage A/Healthy. Of these 52 proteins, 50 were also found in iHFrEF vs. Stage A/Healthy, leaving SLITRK6 and NELL2 expressed in lower levels only in HFpEF. Moreover, 108 proteins, linked to regulation of cell fate commitment, differed only between iHFrEF-HFpEF. Proteomics across the HF spectrum reveals overlap in differentially expressed proteins compared to stage A/Healthy. Multiple proteins are unique for distinguishing iHFrEF from HFpEF, supporting the capacity of proteomics to discern between these conditions.

Serial cardiac biomarkers, pulmonary artery pressures and traditional parameters of fluid status in relation to prognosis in patients with chronic heart failure: Design and rationale of the BioMEMS study.

AIMS: Heart failure (HF), a global pandemic affecting millions of individuals, calls for adequate predictive guidance for improved therapy. Congestion, a key factor in HF-related hospitalizations, further underscores the need for timely interventions. Proactive monitoring of intracardiac pressures, guided by pulmonary artery (PA) pressure, offers opportunities for efficient early-stage intervention, since haemodynamic congestion precedes clinical symptoms. METHODS: The BioMEMS study, a substudy of the MONITOR-HF trial, proposes a multifaceted approach integrating blood biobank data with traditional and novel HF parameters. Two additional blood samples from 340 active participants in the MONITOR-HF trial were collected at baseline, 3-, 6-, and 12-month visits and stored for the BioMEMS biobank. The main aims are to identify the relationship between temporal biomarker patterns and PA pressures derived from the CardioMEMS-HF system, and to identify the biomarker profile(s) associated with the risk of HF events and cardiovascular death. CONCLUSION: Since the prognostic value of single baseline measurements of biomarkers like N-terminal pro-B-type natriuretic peptide is limited, with the BioMEMS study we advocate a dynamic, serial approach to better capture HF progression. We will substantiate this by relating repeated biomarker measurements to PA pressures. This design rationale presents a comprehensive review on cardiac biomarkers in HF, and aims to contribute valuable insights into personalized HF therapy and patient risk assessment, advancing our ability to address the evolving nature of HF effectively.

The perpetual need of randomized clinical trials: challenges and uncertainties in emulating the REDUCE-AMI trial.

Trial emulations in observational data analyses can complement findings from randomized clinical trials, inform future trial designs, or generate evidence when randomized studies are not feasible due to resource constraints and ethical or practical limitations. Importantly, trial emulation designs facilitate causal inference in observational data analyses by enhancing counterfactual thinking and comparisons of real-world observations (e.g. Mendelian Randomization) to hypothetical interventions. In order to enhance credibility, trial emulations would benefit from prospective registration, publication of statistical analysis plans, and subsequent prospective benchmarking to randomized clinical trials prior to their publication. Confounding by indication, however, is the key challenge to interpreting observed intended effects of an intervention as causal in observational data analyses. We discuss the target trial emulation of the REDUCE-AMI randomized clinical trial (ClinicalTrials.gov ID NCT03278509; beta-blocker use in patients with preserved left ventricular ejection fraction after myocardial infarction) to illustrate the challenges and uncertainties of studying intended effects of interventions without randomization to account for confounding. We furthermore directly compare the findings, statistical power, and clinical interpretation of the results of the REDUCE-AMI target trial emulation to those from the simultaneously published randomized clinical trial. The complexity and subtlety of confounding by indication when studying intended effects of interventions can generally only be addressed by randomization.

Timing of Complete Revascularization Stratified by Index Presentation During On- and Off-Hours.

Recent trials suggested immediate complete revascularization (ICR) as a safe alternative to staged complete revascularization (SCR), but the impact of the respective percutaneous coronary intervention strategies between on- versus off-hours is unclear. On-hours was defined as an index revascularization performed between 8:00 a.m. and 6:00 p.m., Monday to Friday, or else the procedure was defined as performed during off-hours. The primary end point consisted of a composite of all-cause mortality, myocardial infarction, unplanned ischemia-driven revascularization, and cerebrovascular events at 1-year follow-up. We used Cox regression models to relate randomized treatment with study end points. We evaluated multiplicative and additive interactions between on- versus off-hours and randomized treatment. The BIOVASC (Percutaneous Complete Revascularization Strategies Using Sirolimus Eluting Biodegradable Polymer Coated Stents in Patients Presenting With Acute Coronary Syndromes and Multivessel Disease) trial enrolled 1,097 and 428 patients during on- and off-hours, respectively. Patients randomized during off-hours were more likely to present with ST-segment elevation myocardial infarction (66.4% vs 29.5%, p <0.001). The composite primary outcome occurred in 8.4% and 10.1% of patients randomized to ICR and SCR, respectively, during on-hours (hazard ratio 0.80, 95% confidence interval 0.54 to 1.19). During off-hours, the primary composite outcome occurred in 5.4% and 7.7% in ICR and SCR (0.69, 95% confidence interval 0.32 to 1.46) with no evidence of a differential effect (interaction pmultiplicative = 0.70, padditive = 0.56). No differential effect was found between treatment allocation and on- versus off-hours in any of the secondary outcomes. In conclusion, no differential treatment effect was found when comparing ICR versus SCR in patients presenting with acute coronary syndrome and multivessel disease during on- or off-hours.

Pulmonary artery pressure monitoring in chronic heart failure: effects across clinically relevant subgroups in the MONITOR-HF trial.

BACKGROUND AND AIMS: In patients with chronic heart failure (HF), the MONITOR-HF trial demonstrated the efficacy of pulmonary artery (PA)-guided HF therapy over standard of care in improving quality of life and reducing HF hospitalizations and mean PA pressure. This study aimed to evaluate the consistency of these benefits in relation to clinically relevant subgroups. METHODS: The effect of PA-guided HF therapy was evaluated in the MONITOR-HF trial among predefined subgroups based on age, sex, atrial fibrillation, diabetes mellitus, left ventricular ejection fraction, HF aetiology, cardiac resynchronization therapy, and implantable cardioverter defibrillator. Outcome measures were based upon significance in the main trial and included quality of life-, clinical-, and PA pressure endpoints, and were assessed for each subgroup. Differential effects in relation to the subgroups were assessed with interaction terms. Both unadjusted and multiple testing adjusted interaction terms were presented. RESULTS: The effects of PA monitoring on quality of life, clinical events, and PA pressure were consistent in the predefined subgroups, without any clinically relevant heterogeneity within or across all endpoint categories (all adjusted interaction P-values were non-significant). In the unadjusted analysis of the primary endpoint quality-of-life change, weak trends towards a less pronounced effect in older patients (Pinteraction = .03; adjusted Pinteraction = .33) and diabetics (Pinteraction = .01; adjusted Pinteraction = .06) were observed. However, these interaction effects did not persist after adjusting for multiple testing. CONCLUSIONS: This subgroup analysis confirmed the consistent benefits of PA-guided HF therapy observed in the MONITOR-HF trial across clinically relevant subgroups, highlighting its efficacy in improving quality of life, clinical, and PA pressure endpoints in chronic HF patients.

Quality-of-life and beliefs about medication in relation to a therapy adherence intervention in resistant hypertension: the Resistant HYpertension: MEasure to ReaCh Targets trial.

OBJECTIVE: To assess the impact of personalized feedback on therapy adherence testing results on quality of life and beliefs about medication in patients with resistant hypertension, as well as to identify patient-oriented predictors of therapy adherence. METHODS: This study was a prespecified post hoc analysis of the multicenter randomized controlled trial Resistant HYpertension: MEasure to ReaCh Targets (RHYME-RCT). Patients were randomized to a personalized feedback conversation on measured antihypertensive drug levels additional to standard-of-care, or standard-of-care only. The primary outcomes consisted of EuroQol EQ-5D-5L and Beliefs about Medicine Questionnaire (BMQ) scores at 12 months. RESULTS: A total of 56 patients with median age 61.5 [25th-75th percentile: 55.8-69.3] years (21.4% women) were included. Mean blood pressure ±SD was 149.8/84.1 ±â€Š14.9/13.8 mmHg while being on a median of 5.6 [4.8-7.3] defined daily dosages (DDD) of antihypertensive drugs. At 12 months, no differences were observed in EQ-5D-5L index (0.81 [0.69-0.89] vs. 0.89 [0.73-1.00]; P  = 0.18) and visual analogue scale score on general patient-perceived health (70 [60-80] vs. 70 [60-82]; P  = 0.53) between the intervention-arm and the standard-of-care only-arm. Likewise, individual EQ-5D-5L domain scores and BMQ scores did not differ between both arms. Irrespective of the intervention, independent positive predictors of the percentage adherence were patient age, EQ-5D-5L index score, BMQ-specific necessity score and concern score, whereas the total number of drugs prescribed was a negative predictor. CONCLUSION: Within this prespecified subanalysis of the randomized RHYME-RCT trial, implementation of a personalized feedback conversation targeting therapy adherence did not improve health-related quality-of-life and beliefs about medication in patients with resistant hypertension.

Immediate or staged complete revascularisation in patients presenting with acute coronary syndrome by number of diseased vessels: a substudy of the BIOVASC randomised trial.

BACKGROUND: In patients presenting with acute coronary syndrome (ACS), the number of diseased vessels may affect the efficacy of a complete revascularisation strategy. AIMS: The authors sought to evaluate the safety and efficacy of immediate complete revascularisation (ICR) and staged complete revascularisation (SCR) in patients presenting with ACS stratified by the number of diseased vessels. METHODS: In this prespecified analysis of the BIOVASC trial, ICR was compared with SCR in patients with two-vessel disease (2VD) or three-vessel disease (3VD). The primary endpoint was a composite of all-cause mortality, myocardial infarction (MI), any unplanned ischaemia-driven revascularisation or cerebrovascular events at 1 year after the index procedure. Comparisons were performed using Cox regression. RESULTS: A total of 1,525 patients were enrolled in the BIOVASC trial, of whom 1,177 presented with 2VD and 265 with 3VD. In the 2VD group, 613 patients were assigned to ICR and 564 to SCR. In the 3VD group, 117 patients were assigned to ICR and 148 to SCR. ICR and SCR led to similar results in both the 2VD (hazard ratio [HR] 0.76, 95% confidence interval [CI]: 0.50-1.13; p=0.18) and 3VD groups (HR 0.79, 95% CI: 0.39-1.59; p=0.51) (pinteraction=0.91) in terms of the primary endpoint. ICR was associated with a lower rate of MI in patients with 3VD (HR 0.21, 95% CI: 0.046-0.93; p=0.04) (pinteraction=0.30). CONCLUSIONS: ICR might be an option in patients presenting with extensive 3VD and might be associated with a lower rate of myocardial infarction compared with SCR.

Timing of Complete Multivessel Revascularization in Patients Presenting With Non-ST-Segment Elevation Acute Coronary Syndrome.

BACKGROUND: Complete revascularization of the culprit and all significant nonculprit lesions in patients with non-ST-segment elevation acute coronary syndrome (NSTE-ACS) and multivessel disease (MVD) reduces major adverse cardiac events, but optimal timing of revascularization remains unclear. OBJECTIVES: This study aims to compare immediate complete revascularization (ICR) and staged complete revascularization (SCR) in patients presenting with NSTE-ACS and MVD. METHODS: This prespecified substudy of the BIOVASC (Percutaneous Complete Revascularization Strategies Using Sirolimus Eluting Biodegradable Polymer Coated Stents in Patients Presenting With Acute Coronary Syndrome and Multivessel Disease) trial included patients with NSTE-ACS and MVD. Risk differences of the primary composite outcome of all-cause mortality, myocardial infarction (MI), unplanned ischemia-driven revascularization (UIDR), or cerebrovascular events and its individual components were compared between ICR and SCR at 1 year. RESULTS: The BIOVASC trial enrolled 1,525 patients; 917 patients presented with NSTE-ACS, of whom 459 were allocated to ICR and 458 to SCR. Incidences of the primary composite outcome were similar in the 2 groups (7.9% vs 10.1%; risk difference 2.2%; 95% CI: -1.5 to 6.0; P = 0.15). ICR was associated with a significant reduction of MIs (2.0% vs 5.3%; risk difference 3.3%; 95% CI: 0.9 to 5.7; P = 0.006), which was maintained after exclusion of procedure-related MIs occurring during the index or staged procedure (2.0% vs 4.4%; risk difference 2.4%; 95% CI: 0.1 to 4.7; P = 0.032). UIDRs were also reduced in the ICR group (4.2% vs 7.8%; risk difference 3.5%; 95% CI: 0.4 to 6.6; P = 0.018). CONCLUSIONS: ICR is safe in patients with NSTE-ACS and MVD and was associated with a reduction in MIs and UIDRs at 1 year.

Temporal evolution of liver function parameters predicts clinical outcome in chronic heart failure patients (Bio-SHiFT study).

BACKGROUND: Liver dysfunction contributes to worse clinical outcomes in heart failure (HF) patients. However, studies exploring temporal evolutions of liver function parameters in chronic HF (CHF) pa- tients, and their associations with clinical outcome, are scarce. Detailed temporal patterns of alkaline phosphatase (ALP), gamma glutamyl transpeptidase (GGTP), total bilirubin (TBIL) and albumin (ALB) were investigated, and their relation with clinical outcome, in patients with stable CHF with reduced ejection fraction. METHODS: Tri-monthly plasma samples were collected from 250 patients during 2.2 (1.4-2.5) years of follow-up. ALP, GGTP, ALB, and TBIL were measured in 749 selected samples and the relationship between repeatedly measured biomarker levels and the primary endpoint (PEP; composite of cardiovas- cular death, heart transplantation, left ventricular assist device implantation, and hospitalization for worsened HF) was evaluated by joint models. RESULTS: Mean age was 66 ± 13 years; 74% were men, 25% in New York Heart Association class III-IV. 66 (26%) patients reached the PEP. Repeatedly measured levels of TBIL, ALP, GGTP, and ALB were associated with the PEP after adjustment for N-terminal prohormone B-type natriuretic peptide and high sensitivity troponin T (hazard ratio [95% confidence interval] per doubling of biomarker level: 1.98 [1.32; 2.95], p = 0.002; 1.84 [1.09; 3.05], p = 0.018, 1.33 [1.08; 1.63], p = 0.006 and 1.14 [1.09; 1.20], p < 0.001, respectively). Serial levels of ALP and GGTP, and slopes of the temporal evolutions of ALB and TBIL, adjusted for clinical variables, were also significantly associated with the PEP. CONCLUSIONS: Changes in serum levels of TBIL, ALP, GGTP, and ALB precede adverse cardiovascular events in patients with CHF. These routine liver function parameters may provide additional prognostic information in heart failure with reduced ejection fraction patients in clinical practice.

Sex Differences in Diagnosis, Treatment, and Cardiovascular Outcomes in Homozygous Familial Hypercholesterolemia.

Importance: Homozygous familial hypercholesterolemia (HoFH) is a rare genetic condition characterized by extremely increased low-density lipoprotein (LDL) cholesterol levels and premature atherosclerotic cardiovascular disease (ASCVD). Heterozygous familial hypercholesterolemia (HeFH) is more common than HoFH, and women with HeFH are diagnosed later and undertreated compared to men; it is unknown whether these sex differences also apply to HoFH. Objective: To investigate sex differences in age at diagnosis, risk factors, lipid-lowering treatment, and ASCVD morbidity and mortality in patients with HoFH. Design, Setting, and Participants: Sex-specific analyses for this retrospective cohort study were performed using data from the HoFH International Clinical Collaborators (HICC) registry, the largest global dataset of patients with HoFH, spanning 88 institutions across 38 countries. Patients with HoFH who were alive during or after 2010 were eligible for inclusion. Data entry occurred between February 2016 and December 2020. Data were analyzed from June 2022 to June 2023. Main Outcomes and Measures: Comparison between women and men with HoFH regarding age at diagnosis, presence of risk factors, lipid-lowering treatment, prevalence, and onset and incidence of ASCVD morbidity (myocardial infarction [MI], aortic stenosis, and combined ASCVD outcomes) and mortality. Results: Data from 389 women and 362 men with HoFH from 38 countries were included. Women and men had similar age at diagnosis (median [IQR], 13 [6-26] years vs 11 [5-27] years, respectively), untreated LDL cholesterol levels (mean [SD], 579 [203] vs 596 [186] mg/dL, respectively), and cardiovascular risk factor prevalence, except smoking (38 of 266 women [14.3%] vs 59 of 217 men [27.2%], respectively). Prevalence of MI was lower in women (31 of 389 [8.0%]) than men (59 of 362 [16.3%]), but age at first MI was similar (mean [SD], 39 [13] years in women vs 38 [13] years in men). Treated LDL cholesterol levels and lipid-lowering therapy were similar in both sexes, in particular statins (248 of 276 women [89.9%] vs 235 of 258 men [91.1%]) and lipoprotein apheresis (115 of 317 women [36.3%] vs 118 of 304 men [38.8%]). Sixteen years after HoFH diagnosis, women had statistically significant lower cumulative incidence of MI (5.0% in women vs 13.7% in men; subdistribution hazard ratio [SHR], 0.37; 95% CI, 0.21-0.66) and nonsignificantly lower all-cause mortality (3.0% in women vs 4.1% in men; HR, 0.76; 95% CI, 0.40-1.45) and cardiovascular mortality (2.6% in women vs 4.1% in men; SHR, 0.87; 95% CI, 0.44-1.75). Conclusions and Relevance: In this cohort study of individuals with known HoFH, MI was higher in men compared with women yet age at diagnosis and at first ASCVD event were similar. These findings suggest that early diagnosis and treatment are important in attenuating the excessive cardiovascular risk in both sexes.