Baim Institute for Clinical Research

Safety and efficacy of short-term ventricular assist devices (VAD) remains incompletely understood, particularly in younger children. This systematic review and meta-analysis aims to evaluate outcomes, including bridging success, complications, and mortality, associated with short-term VAD support in paediatric heart transplant candidates. A systematic search of PubMed, EMBASE, CINAHL, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, Scopus, and Web of Science was conducted from inception to 2 December 2024. Eligible studies reported patients ≤ 18 years supported by short-term VADs. This review was registered in PROSPERO (ID: CRD42023468125). Twelve retrospective studies met the inclusion criteria, encompassing 532 paediatric patients (mean age 10.0 years, < 0.1–18.3, mean weight 39.5 ± 30.3 kg). Pooled proportions show that with a mean support duration of 15.2 days, 50.7% were successfully bridged to transplant (95% CI 36.4%, 65.0%; I2 = 91.1%) with a 24.8% waitlist mortality (95% CI 17.6%, 31.9%; I2 = 63.8%), 14.0% (95% CI 7.2%, 20.9%; I2 = 97.5%) weaned off support and 5.4% (95% CI 2.6%, 8.3%; I2 = 39.1%) remaining on support. Complication rates were high with haemorrhage (38.9%), renal impairment (35.2%), cerebrovascular events (29.5%), infection (17.8%), and thromboembolism (9.9%) being the most reported. Short-term VADs offer a feasible bridge to transplant in paediatric patients, with success rates comparable to registry data. However, high rates of serious complications and waitlist mortality persist, particularly in these younger children. These findings demonstrate the need for improved patient selection, standardized outcome reporting, and development of safer, size-appropriate devices for paediatric use.

Background and Objectives Observational data can provide evidence of treatment effects in a low-burden, cost-effective manner. Using a causal inference framework to address selection bias, we illustrate the approach in ALS by examining previously researched associations, baseline function and sex, and evaluating metformin’s survival benefits. Methods Data are from the ALS Natural History Study collected in the United States, Israel, and Italy from 2015 to 2025. We employ propensity score matching, two approaches to address loss to follow-up (i.e. a naive exclusion and principal stratification), and randomization-based inference to evaluate difference in 18-month restricted mean survival time. Results For the function investigation, estimated survival is 16.39, 16.14, 16.09, and 16.24 months for the high ALSFRS-R group and 14.04, 14.42, 14.72, and 14.60 months for the low ALSFRS-R group using the non imputed and imputed datasets 1-3, respectively (p&lt;0.0001, N=450; p&lt;0.00001, N=1,485; p&lt;0.00001, N=1,492; p&lt;0.00001, N=1,600). Using principal stratification, estimated survival is 16.38, 16.14, 16.09, and 16.23 months for the high ALSFRS-R group and 14.04, 14.42, 14.72, and 14.59 months for the low ALSFRS-R group with the non imputed and imputed datasets 1-3, respectively (p&lt;0.0001, N=449; p&lt;0.00001, N=1,483; p&lt; 0.00001, N=1,491; p&lt;0.00001, N=1,596). For the sex investigation, estimated survival is 15.20, 15.16, 15.20, and 15.17 months for females and 15.41, 14.84, 14.91, and 14.97 months for males using the non imputed and imputed datasets 1-3, respectively (p≈0.594, N=612; p≈0.155, N=2,081; p≈0.200, N=2,104; p≈0.359, N=2,111). Using principal stratification, estimated survival is 15.20, 15.16, 15.20, and 15.17 months for females and 15.41, 14.83, 14.91, and 14.97 months for males with the non imputed and imputed datasets 1-3, respectively (p≈0.598, N=612; p≈0.146, N=2,079; p≈0.195, N=2,102; p≈0.364, N=2,110). For the metformin investigation, estimated survival is 14.77, 14.87, and 14.57 months for metformin users and 14.59, 14.43, and 13.97 months for non metformin users using imputed datasets 1-3, respectively (p≈0.391, N=289; p≈0.257, N=279; p≈0.191, N=301). Using principal stratification, estimated survival is 14.75, 14.85, and 14.55 months for metformin users and 14.68, 14.58, and 13.97 months for non metformin users with imputed datasets 1-3, respectively (p≈0.458, N=286; p≈0.351, N=275; p≈0.201, N=300). Discussion We reject the sharp null hypothesis for the function investigation and fail to reject it for the sex and metformin investigations. Trial Registration Information ClinicalTrials.gov Identifier: NCT05966038 .

Antiphospholipid antibodies (aPL) are directed against phospholipids and phospholipid-binding proteins. Laboratory assays used to detect aPL include serological tests for aPL against β2-glycoprotein 1, cardiolipin and other molecules, as well as functional assays for lupus anticoagulant. The presence of aPL can lead to endothelial dysfunction or a hypercoagulable state through prothrombotic and antifibrinolytic mechanisms. These processes, often in conjunction with a 'second hit', such as trauma, surgery, or other causes of hypercoagulability or stasis, can lead to venous or arterial thrombosis. The thrombotic risk associated with aPL is best recognized in thrombotic antiphospholipid syndrome, characterized by a persistently positive test for lupus anticoagulant or seropositivity for aPL associated with venous, arterial or microvascular thrombosis. However, aPL seropositivity and its clinical effect on thrombotic events have been increasingly recognized in a broader group of individuals who do not meet traditional research criteria for thrombotic antiphospholipid syndrome. In this Review, we provide an overview of the evidence related to aPL seropositivity in individuals with or without previous thrombosis and the clinical relevance of aPL seropositivity in predicting the risk of thrombotic cardiovascular events. We discuss potential management strategies and identify key knowledge gaps that warrant further research.

Drug-coated balloons are the preferred treatment for in-stent restenosis (ISR), avoiding the need for a second metallic layer. While both paclitaxel-coated balloons (PCB) and limus-coated balloons (LCB, typically sirolimus or biolimus) are used, direct comparative evidence is limited, particularly regarding their long-term angiographic efficacy and clinical safety. We conducted a systematic review and study-level meta-analyzis of studies comparing LCB with PCB for coronary ISR. A comprehensive search was performed across PubMed, Embase, Cochrane, Scopus, Web of science for randomized controlled trials. Outcomes were compared using risk ratios (RR) for categorical data and mean differences for continuous data in a random-effects model. Heterogeneity was assessed using the I2 statistic. Six randomized controlled trials involving 1,038 patients were included (552 in the LCB group and 481 in the PCB group). Compared with PCB, LCB were associated with a significantly higher risk of clinically driven target lesion revascularization (RR: 1.48; 95% CI: 1.02 to 2.14; p = 0.04; I2 = 0%) and target lesion failure (RR: 1.19; 95% CI: 0.87 to 1.62; p = 0.27; I2 = 0%). In contrast, both platforms demonstrated no differences in all-cause mortality (RR: 0.98; p = 0.96), myocardial infarction (RR: 0.73; p = 0.46), stent thrombosis (RR: 0.66; p = 0.57), or MACE (RR: 1.09; p = 0.58). Angiographic outcomes were comparable, including late lumen loss (mean differences: -0.00 mm; p = 0.65; I2 = 74.7%) and minimal lumen diameter (mean differences: -0.12 mm; p = 0.07). In patients with ISR, PCB reduced repeat revascularization compared with LCB. These data suggest a modest advantage for PCB in preventing restenosis following drug-coated balloon angioplasty for ISR.

Abstract GLP-1 receptor agonist (GLP-1RA) discontinuation has been associated with weight regain. However, the real-world association between discontinuation of GLP-1RA prescriptions and weight change has not been explored. We assessed weight trajectories of 4,182 patients in the six months following their last GLP-1RA prescription. Approximately two-thirds of patients showed stable weight or continued weight loss during this period post the last known GLP-1RA prescription. In a representative subset of patients with clinician-documented discontinuation near the last prescription (N=300), a similar distribution of weight regain in a minority of patients was observed vs no regain in the majority of patients during the six-month post-GLP-1RA prescription period. To mirror clinical trial-style discontinuation definitions, we also evaluated cohorts with no subsequent GLP-1RA prescription for 1 year after the last prescription (semaglutide N=1,755; tirzepatide N=1,312), observing weight regain in a minority of patients (39.3% semaglutide; 26.6% tirzepatide) and no weight regain in the majority (60.7% semaglutide; 73.4% tirzepatide) in the year following the last known GLP-1RA prescription. Exercise counseling was documented more frequently among patients with durable weight loss post-last GLP1 prescription compared with those with weight regain (26.2% vs. 14.7%; p=0.04). Further studies are warranted to infer the mechanisms underlying these real-world patterns.

BackgroundAdherence to lipid-lowering therapy (LLT) guidelines is suboptimal, leading to poor achievement of low-density lipoprotein cholesterol (LDL-C) goals and elevated risk for atherosclerotic cardiovascular disease (ASCVD) events.ObjectivesThe purpose of this study was to determine whether an educational intervention targeting physicians improves optimization of LLT over 1 year for patients with ASCVD.MethodsGOULD (Getting to an Improved Understanding of Low-Density Lipoprotein Cholesterol and Dyslipidemia Management) EDU (Education) was a 1-year extension in a subset of sites in the GOULD prospective, observational registry of United States patients with ASCVD. In a cluster-randomized, stepped-wedge design, sites were randomized to 2 waves of an educational intervention that included 2 webinars and access to interactive data reports showing site-specific performance alongside full-study data over the course of the study. Chart reviews assessed LLTs and patient outcomes. Outcomes assessed over 1 year included change in prescribed LLT, frequency of measurement of LDL-C, LDL-C levels, LDL-C goal achievement, and responses on a structured physician questionnaire.ResultsThirty sites were randomized to Step 1 (n = 616) and 26 sites to Step 2 (n = 382). The mean (SD) age was 70.2 (9.6) years, 61.1% (610/998) were male, and 85.3% (851/998) were White. During the study, 83.6% (820/981) of patients had no change in LLT, and intensification occurred in only 7.0% (69/981); intensification did not differ by intervention step. The percentage of patients who met the goal of LDL-C <70 mg/dL was 39.0% (202/518) at baseline and 39.5% (252/638) at 1 year.ConclusionsAn educational intervention with physicians had little impact on LLT optimization or LDL-C goal achievement in patients with ASCVD over a 1-year period. Novel approaches are needed to improve LDL-C goal achievement. (Getting to an Improved Understanding of Low-Density Lipoprotein Cholesterol and Dyslipidemia Management [GOULD] a Registry of High Cardiovascular Risk Subjects in the United States; NCT02993120)

Obicetrapib is a potent, selective cholesteryl ester transfer protein (CETP) inhibitor that significantly lowers low-density lipoprotein cholesterol (LDL-C). Additive reductions in LDL-C occur when obicetrapib is combined with ezetimibe. The impact of obicetrapib and ezetimibe fixed-dose combination (FDC) on coronary plaque burden is unknown. Favorable changes in noncalcified coronary atherosclerotic plaque volume (NCPV) may indicate a potential beneficial effect on atherosclerotic cardiovascular disease (ASCVD) events. REMBRANDT is a placebo-controlled, double-blind, randomized trial designed to assess the efficacy of obicetrapib and ezetimibe FDC on coronary plaque burden. Individuals aged 45 years or older with ASCVD (imaging evidence of vascular disease or clinically manifested ASCVD) and an LDL-C of ≥70 mg/dL despite maximally tolerated lipid-modifying therapy are eligible to participate. Eligible participants (N = 300) will be randomized in a 1:1 ratio to obicetrapib 10 mg and ezetimibe 10 mg FDC once daily or placebo tablet once daily. The primary efficacy outcome of REMBRANDT is percent change in total NCPV from baseline to 18 months as assessed by coronary computed tomographic angiography (CCTA). Secondary endpoints include absolute change in total NCPV, percent and absolute change in NCPV in the most diseased coronary segment, percent change in LDL-C, and change in perivascular fat attenuation index from baseline to 18 months. The REMBRANDT trial will determine whether the favorable effects of obicetrapib and ezetimibe FDC on LDL-C translate to a reduction in coronary plaque burden as a potential mechanism for ASCVD risk reduction. NCT06305559.

Blood pressure (BP) management in older adults is complex because of age-related physiological changes and uncertainty around ideal systolic BP (SBP) targets. Heart stress (HS), defined by age-adjusted elevation in NT-proBNP (N-terminal pro-B-type natriuretic peptide) levels, may improve cardiovascular disease (CVD) risk stratification and support more individualized BP management. We conducted a post hoc analysis of ASPREE (Aspirin in Reducing Events in the Elderly) involving 11 941 community-dwelling older adults without CVD at enrollment (mean age, 75.1 years; 53.5% women). HS was defined by NT-proBNP ≥150 pg/mL for participants 65 to 74 years of age and ≥300 pg/mL for participants ≥75 years of age. Participants were categorized into 4 groups by hypertension and HS status. The primary outcome was total CVD events (a composite of nonfatal myocardial infarction, fatal or nonfatal stroke, coronary heart disease death, or hospitalization for heart failure). Associations between hypertension and SBP with total CVD events were examined by HS status using Cox proportional-hazards models and restricted cubic spline. SBP was evaluated categorically (<120, 120-129, 130-139, 140-159, or ≥160 mm Hg) and continuously. A landmark sensitivity analysis excluded participants with CVD events or censoring in the first 2 years, with follow-up starting at year 3. HS was present in 25.8% of participants. Compared with the reference group (no hypertension or HS), adjusted hazard ratios (95% CI) for total CVD events were 1.41 (1.18-1.70) for hypertension + no HS, 1.79 (1.34-2.39) for no hypertension + HS, and 2.32 (1.89-2.84) for hypertension + HS (Ptrend<0.001). Among participants without HS, the lowest incidence of total CVD events occurred at SBP 130 to 139 mm Hg, showing a U-shaped association across SBP levels (Pnonlinearity=0.011). Among participants with HS, risk increased linearly with SBP (Plinear trend=0.85) and was lowest at SBP <120 mm Hg. Landmark analyses yielded generally consistent findings. HS is common in older adults and jointly associated with hypertension and increased CVD risk. The SBP-CVD relationship differs by HS status, suggesting a potential value of HS for guiding individualized BP management. Prospective studies are warranted to determine whether HS-guided strategies improve BP control and reduce CVD risk in older adults.