Lipoprotein(a) and Calcific Aortic Valve Stenosis Progression: A Systematic Review and Meta-Analysis.

Importance: There are currently no pharmacological treatments available to slow hemodynamic progression of aortic stenosis. Plasma lipoprotein(a) concentrations predict incident aortic stenosis but its association with hemodynamic progression is controversial. Objective: To determine the association between plasma lipoprotein(a) concentrations and hemodynamic progression in patients with aortic stenosis. Design, Settings and Participants: The study included patients with aortic stenosis from 5 longitudinal clinical studies conducted from March 2001 to March 2023 in Canada and the UK. Of 757 total patients, data on plasma lipoprotein(a) concentrations and rates of hemodynamic progression assessed by echocardiography were available for 710, who were included in this analysis. Data were analyzed from March 2023 to April 2024. Exposure: Cohort-specific plasma lipoprotein(a) concentration tertiles. Main Outcomes and Measures: Hemodynamic aortic stenosis progression on echocardiography as assessed by annualized change in peak aortic jet velocity, mean transvalvular gradient, and aortic valve area. Results: Among the included patients, 497 (70%) were male and 213 (30%) were female. The mean (SD) age was 65.2 (13.1) years. Patients in the top lipoprotein(a) tertile demonstrated 41% (estimate, 1.41; 95% CI, 1.13-1.75) faster progression of peak aortic jet velocity and 57% (estimate, 1.57; 95% CI, 1.18-2.10) faster progression of mean transvalvular gradient than patients in the bottom tertile. There was no evidence of heterogeneity across the individual cohorts. Progression of aortic valve area was comparable between groups (estimate, 1.23; 95% CI, 0.71-2.12). Similar results were observed when plasma lipoprotein(a) concentrations were treated as a continuous variable. Conclusions and Relevance: In this study, higher plasma lipoprotein(a) concentrations were associated with faster rates of hemodynamic progression in patients with aortic stenosis. Lowering plasma lipoprotein(a) concentrations warrants further investigation in the prevention and treatment of aortic stenosis.

Multi-modality imaging in aortic stenosis: an EACVI clinical consensus document.

In this EACVI clinical scientific update, we will explore the current use of multi-modality imaging in the diagnosis, risk stratification, and follow-up of patients with aortic stenosis, with a particular focus on recent developments and future directions. Echocardiography is and will likely remain the key method of diagnosis and surveillance of aortic stenosis providing detailed assessments of valve haemodynamics and the cardiac remodelling response. Computed tomography (CT) is already widely used in the planning of transcutaneous aortic valve implantation. We anticipate its increased use as an anatomical adjudicator to clarify disease severity in patients with discordant echocardiographic measurements. CT calcium scoring is currently used for this purpose; however, contrast CT techniques are emerging that allow identification of both calcific and fibrotic valve thickening. Additionally, improved assessments of myocardial decompensation with echocardiography, cardiac magnetic resonance, and CT will become more commonplace in our routine assessment of aortic stenosis. Underpinning all of this will be widespread application of artificial intelligence. In combination, we believe this new era of multi-modality imaging in aortic stenosis will improve the diagnosis, follow-up, and timing of intervention in aortic stenosis as well as potentially accelerate the development of the novel pharmacological treatments required for this disease.

Effect of race on pressure recovery adjustment for prevention of aortic stenosis grading discordance.

OBJECTIVE: We sought to evaluate the potential impact of racial difference (Asians vs Caucasians) on the clinical usefulness of pressure recovery (PR) adjustment for preventing discordant aortic stenosis (AS) grading in patients with severe AS. METHODS: Data from 1450 patients (mean age, 70.2±10.6 years; 290 (20%) Caucasians; aortic valve area (AVA), 0.77±0.26 cm2) were retrospectively analysed. PR-adjusted AVA was calculated using a validated equation. Discordant grading of severe AS was defined as AVA of <1.0 cm2 and mean gradient of <40 mm Hg. The frequency of discordant grading was assessed in the overall cohort and the propensity score-matched cohort. RESULTS: Before PR adjustment, 1186 patients showed AVA values of <1.0 cm2; after PR adjustment, 170 (14.3%) were reclassified as having moderate AS. PR adjustment decreased the frequency of discordant grading from 31.4% to 14.1% in Caucasians and from 13.8% to 7.9% in Asians. Patients with reclassification to moderate AS after PR adjustment had a significantly lower risk of a composite of aortic valve replacement or all-cause death than did those with severe AS after PR adjustment (HR 0.38; 95% CI 0.31-0.46; p<0.001). In propensity score-matched cohorts (173 pairs), the frequency of discordant grading before PR adjustment was 42.2% and 43.9% in the Caucasian and Asian patients, respectively, which decreased to 21.4% and 20.2%, respectively, after PR adjustment. CONCLUSIONS: Clinically relevant PR occurred, regardless of race in patients with moderate to severe AS. Routine PR adjustment may be useful for reconciling discordant AS grading.

Ticagrelor in the management of coronary artery disease.

Ticagrelor is a potent and orally active P2Y12 inhibitor. Ticagrelor has been extensively tested in Phase II and Phase III trials in patients with coronary artery disease. The pharmacokinetics and pharmacodynamics of ticagrelor result in more rapid and effective inhibition of platelet activation compared with other P2Y12 inhibitors. This has resulted in a reduction in recurrent major cardiovascular events in initial randomized controls trials comparing ticagrelor with clopidogrel. More recently, clinical trials have investigated the use of ticagrelor in patients with stable coronary artery disease and a high residual risk of coronary thrombotic events. In patients with stable coronary artery disease, the potent antiplatelet effect of ticagrelor is counterbalanced by an increased risk of major bleeding. Further research is ongoing to determine the optimal duration of ticagrelor therapy.

Non-invasive imaging of high-risk coronary plaque: the role of computed tomography and positron emission tomography.

Despite recent advances, cardiovascular disease remains the leading cause of death globally. As such, there is a need to optimise our current diagnostic and risk stratification pathways in order to better deliver individualised preventative therapies. Non-invasive imaging of coronary artery plaque can interrogate multiple aspects of coronary atherosclerotic disease, including plaque morphology, anatomy and flow. More recently, disease activity is being assessed to provide mechanistic insights into in vivo atherosclerosis biology. Molecular imaging using positron emission tomography is unique in this field, with the potential to identify specific biological processes using either bespoke or re-purposed radiotracers. This review provides an overview of non-invasive vulnerable plaque detection and molecular imaging of coronary atherosclerosis.