Commentary by JACC: Clinical Electrophysiology Deputy Editor Francis Marchlinski, MD.

Polygenic risk scores showed associations with several cardiometabolic outcomes in breast cancer survivors but did not improve prediction beyond traditional clinical factors. Their performance varied across ancestry groups and was weakened in patients exposed to cardiotoxic therapies, highlighting limits of current genetic risk tools.

This study of 801 multiple myeloma patients found that atrial fibrillation occurred in 5.5% within 90 days after autologous stem cell transplantation—nearly double previously reported rates—indicating disease‑specific risks. AF strongly predicted mortality from non‑relapse causes and may serve as a marker of physiological vulnerability, emphasizing the value of expanded pre‑transplant cardiac assessment and monitoring.

Researchers used genome‑wide CRISPR/Cas9 loss‑of‑function screens in cardiomyocytes to identify RARA and SPNS1 as key modulators of doxorubicin cardiotoxicity, highlighting pathways that influence both injury susceptibility and intracellular drug handling. Activation of RARA reduced toxicity without impairing anticancer effects, while SPNS1 loss caused harmful drug accumulation, offering new mechanistic insights and potential therapeutic targets.

This study analyzes over 2,600 transthyretin V142I variant carriers in the Million Veteran Program and finds significantly elevated risks of heart failure, cardiomyopathy, arrhythmias, neuropathy, and musculoskeletal complications compared with matched controls. Despite these risks, amyloidosis was rarely diagnosed clinically, underscoring major gaps in recognition and the need for earlier identification and multidisciplinary intervention.

JACC: CardioOncology Volume 8 Issue 1 Full Issue Summary with Introduction by Dr. Bonnie Ky, Editor-in-Chief

Mirza Umair Khalid, MD, Social Media Editor for JACC: Cardiovascular Interventions, and Mattio Galli, MD, PhD, discuss a recently published original research paper analyzing the role of genotype-guided escalation or de-escalation of antiplatelet therapy in acute coronary syndrome (ACS).

Mirza Umair Khalid, MD, Social Media Editor for JACC: Cardiovascular Interventions, and Rikke Sørensen, MD, PhD, discuss a recently published original research paper from DanGer Shock substudy analyzing the bleeding events in patients with infarct related cardiogenic shock.