Upstream targeting for the prevention of atrial fibrillation: Targeting Risk Interventions and Metformin for Atrial Fibrillation (TRIM-AF)-rationale and study design.

Background: Despite advances in ablation and other therapies for AF, progression of atrial fibrillation (AF) remains a significant clinical problem, associated with worse prognosis and worse treatment outcomes. Upstream therapies targeting inflammatory or antifibrotic mechanisms have been disappointing in preventing AF progression, but more recently genetic and genomic studies in AF suggest novel cellular and metabolic stress targets, supporting prior studies of lifestyle and risk factor modification (LRFM) for AF. However, while obesity is a significant risk factor, weight loss and risk factor modification have not been successfully applied in a US population with AF.

Zerlasiran-A Small-Interfering RNA Targeting Lipoprotein(a): A Phase 2 Randomized Clinical Trial.

Importance: Elevated lipoprotein(a) increases the risk of atherosclerotic cardiovascular disease (ASCVD) and aortic stenosis.

Objective: To evaluate the effects of zerlasiran, a small-interfering RNA targeting hepatic synthesis of apolipoprotein(a), on lipoprotein(a) serum concentration.

Design, Setting, And Participants: A multicenter trial in patients with stable ASCVD with serum lipoprotein(a) concentrations greater than or equal to 125 nmol/L at 26 sites in Europe and South Africa between January 3, 2023, and April 27, 2023, with last follow-up on July 1, 2024.

Mavacamten in Patients With Hypertrophic Cardiomyopathy Referred for Septal Reduction: Week 128 Results from VALOR-HCM.

Background: In severely symptomatic patients with obstructive hypertrophic cardiomyopathy (HCM), VALOR-HCM trial (Study to Evaluate Mavacamten in Adults With Symptomatic Obstructive HCM Who Are Eligible for Septal Reduction Therapy [URL: https://clinicaltrials.gov; Unique identifier: NCT04349072]) reported that mavacamten reduced the short-term need for septal reduction therapy (SRT). The current report examined the longer-term effect of mavacamten through end of treatment at week 128.