Research Appraisals
Evidence-based critical appraisals of the latest medical research, systematically evaluated using Oxford CEBM methodology.
Showing 4 appraisals
The Journal of clinical endocrinology and metabolism
Associations of Metabolic Phenotypes with Cardiac Structure and Clinical Outcomes: Insights from the UK Biobank
CONTEXT: Metabolic syndrome and obesity represent major cardiovascular risk factors, yet their combined effects on cardiac structure and clinical outcomes remain incompletely understood. OBJECTIVE: To examine associations between metabolic phenotypes, cardiac magnetic resonance imaging (CMR), and clinical outcomes. DESIGN: Prospective study with a median 5.1-year follow-up. SETTING: Population-based cohort from the UK Biobank. PARTICIPANTS: A total of 22 789 participants (mean age 64.1 ± 7.5 years, 52.6% female) were categorized as metabolically healthy nonobese (MHN) vs obese (MHO) or unhealthy nonobese (MUN) vs obese (MUO), based on obesity (body mass index ≥30 kg/m²) and metabolic status (prevalent diabetes or both hypertension and hyperlipidemia). MAIN OUTCOME MEASURE(S): Primary and secondary endpoints were major adverse cardiovascular events (MACE) and all-cause mortality, respectively. CMR included left ventricular ejection fraction (LVEF, %), end-diastolic volume (LVEDV, mL), myocardial mass (g), wall thickness (mm), cardiac output (L/min), and left atrial volume (mL). Linear regression and Cox proportional hazards models, adjusted for age, sex, and smoking, assessed associations between metabolic phenotypes, CMR, and clinical outcomes. RESULTS: In adjusted models, all phenotypes demonstrated increased WT (MHO: β=.53 [.50, .55]; MUN: β=.24 [.21, .27]; MUO: β=.66 [.61, .70]), compared to MHN. LVEDV was increased in obesity phenotypes (MHO: β=4.67 [4.07, 5.27]; MUO: β=5.14 [4.05, 6.22]) and decreased in MUN (β=-1.25 [-1.95, -.55]), while MUO showed reduced LVEF (β=-.48 [-.91, -.04]). MACE risk was increased in unhealthy phenotypes (MUN: adjusted hazard ratio (aHR) = 1.55 [1.16-2.07]; MUO: aHR = 1.95 [1.28-2.97]). All phenotypes showed increased all-cause mortality risk (MHO: aHR = 1.65 [1.23-2.21]; MUN: aHR = 1.41 [1.05-1.90]; MUO: 2.10 [1.41-3.15]). CONCLUSION: Metabolic phenotypes show distinct cardiac structural changes and increased mortality risk, supporting their potential in cardiovascular risk stratification.
19 May 2026
Read appraisal →Circulation
Effect of APOC3 Inhibition With Olezarsen on Coronary Atherosclerosis: Essence-TIMI 73b Imaging Study
BACKGROUND: Whether lowering triglyceride-rich lipoproteins and remnant cholesterol favorably modifies coronary atherosclerosis is unclear. Olezarsen, an antisense oligonucleotide that targets apolipoprotein C-III, reduces triglycerides by ~60% and remnant cholesterol by ~70%, has a neutral effect on LDL (low-density lipoprotein) cholesterol (LDL-C), and reduces apoB (apolipoprotein B) by ~15% in moderate hypertriglyceridemia. We investigated the effect of olezarsen on coronary plaque in adults with largely moderate hypertriglyceridemia. METHODS: We conducted a coronary computed tomography angiography study within Essence-TIMI 73b, a randomized, placebo-controlled trial of olezarsen versus placebo that enrolled patients between November 2022 and February 2024. Inclusion criteria were triglycerides ≥150 mg/dL (2.26 mmol/L), presence of or high risk for cardiovascular disease, and, for this imaging study, noncalcified plaque on baseline coronary computed tomography angiography. The primary end point was percent change from baseline to 12 months in noncalcified plaque volume. RESULTS: Of 468 participants (349 olezarsen, 119 placebo), the median age was 63 years (interquartile range, 56-70); 31% were women, and 97% received lipid-lowering therapy. Median baseline triglycerides were 249 mg/dL (interquartile range, 197-331), and remnant cholesterol was 53 mg/dL (interquartile range, 38-76). Median baseline noncalcified plaque volume was 125.3 mm³ (interquartile range, 63.2-213.3). At 6 months, olezarsen reduced triglycerides by 63.9%, remnant cholesterol by 71.9%, and apoB by 16.0% over placebo, with no difference in LDL-C. The percent change in noncalcified plaque volume from baseline to month 12 did not differ between olezarsen and placebo (placebo-adjusted least-squares mean difference, 2.98% [95% CI, -3.4 to 9.3]; p=0.36). No significant differences between olezarsen and placebo were observed for changes in low-attenuation, calcified, or total plaque volumes at 12 months. CONCLUSIONS: Despite substantial triglyceride and remnant cholesterol lowering, treatment with olezarsen for 12 months on top of standard-of-care lipid-lowering therapy in patients with largely moderate hypertriglyceridemia did not affect noncalcified coronary plaque volume. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT05610280.
19 May 2026
Read appraisal →Heart (British Cardiac Society)
Individual hearts: computational models for improved management of cardiovascular disease
Cardiovascular disease remains a leading cause of morbidity and mortality worldwide, with conventional management often applying standardised approaches that struggle to address individual variability in increasingly complex patient populations. Computational models, both knowledge-driven and data-driven, have the potential to reshape cardiovascular medicine by offering innovative tools that integrate patient-specific information with physiological understanding or statistical inference to generate insights beyond conventional diagnostics. This review traces how computational modelling has evolved from theoretical research tools into clinical decision support systems that enable personalised cardiovascular care. We examine this evolution across three key domains: enhancing diagnostic accuracy through improved measurement techniques, deepening mechanistic insights into cardiovascular pathophysiology and enabling precision medicine through patient-specific simulations. The review covers the complementary strengths of data-driven approaches, which identify patterns in large clinical datasets, and knowledge-driven models, which simulate cardiovascular processes based on established biophysical principles. Applications range from artificial intelligence-guided measurements and model-informed diagnostics to digital twins that enable in silico testing of therapeutic interventions in the digital replicas of individual hearts. This review outlines the main types of cardiovascular modelling, highlighting their strengths, limitations and complementary potential through current clinical and research applications. We also discuss future directions, emphasising the need for interdisciplinary collaboration, pragmatic model design and integration of hybrid approaches. While progress is promising, challenges remain in validation, regulatory approval and clinical workflow integration. With continued development and thoughtful implementation, computational models hold the potential to enable more informed decision-making and advance truly personalised cardiovascular care.
14 May 2026
Read appraisal →J Am Coll Cardiol
Contemporary Diagnosis and Treatment of Aortic Regurgitation: A State-of-the-Art Review
Aortic regurgitation (AR) is progressive and frequently under-recognized; without timely intervention it drives adverse left-ventricular remodeling and heart failure. Despite Class I guideline indications, many patients-especially older, frail individuals with multimorbidity-remain untreated. Advancements in high-fidelity multimodality imaging-including cardiac magnetic resonance, 4-dimensional flow, and speckle-tracking echocardiography-have enabled earlier detection of remodeling and more accurate quantification of regurgitant burden. These techniques are redefining thresholds for treatment and may enable biomarker-imaging composite staging of disease. Surgery remains the gold standard of therapy for native AR. Contemporary surgical management is tailored to age, anatomy, and root pathology. Although surgical aortic valve replacement remains the predominant therapy for most candidates, valve-sparing root procedures, the Ross operation, and aortic valve neocuspidization are increasingly offered at experienced centers for carefully selected lower-risk patients. Transcatheter aortic valve replacement is expanding rapidly as a viable option that helps bridge the treatment gap for those at prohibitive or high risk for surgery. Yet, devices optimized for calcific aortic stenosis encounter technical obstacles in native AR-including large, noncalcified annuli, elliptical root geometry, and high stroke volumes-leading to suboptimal anchoring, residual paravalvular regurgitation, and device embolization. Purpose-built AR systems with leaflet-engaging anchoring and enhanced sealing have shown encouraging outcomes in feasibility and pivotal studies and have obtained commercial approval in Europe, and U.S. authorization is anticipated. This state-of-the-art review synthesizes current insights into AR pathophysiology, diagnostic advances, and therapeutic innovations in surgical and transcatheter techniques, highlighting knowledge gaps and proposing research priorities to accelerate access to care for this historically undertreated population.
1 Feb 2026
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