Elevated Lp(a) Linked to Higher Ventricular Arrhythmia Risk in HFrEF: JAMA
A new study published in the Journal of American Medical Association showed that in patients with heart failure with reduced ejection fraction (HFrEF), elevated lipoprotein(a) [Lp(a)] levels were linked to an increased risk of ventricular arrhythmias requiring implanted cardioverter-defibrillator (ICD) therapy, including episodes ended by antitachycardia pacing without shock.
Atherosclerotic cardiovascular disease and unfavorable myocardium remodeling are linked to the genetically determined lipoprotein(a) [Lp(a)]. Myocardial fibrosis-related phenotypes, incident heart failure, and poor cardiovascular outcomes have all been linked to elevated Lp(a).
However, it is unclear if raised Lp(a) identifies a subgroup at higher risk of ventricular tachyarrhythmias necessitating implanted cardioverter-defibrillator (ICD) treatment in patients with heart failure with reduced ejection fraction. This study assessed the relationship between treated ventricular arrhythmias and high Lp(a) in persons with HFrEF receiving ICD implantation.
Adults with a left ventricular ejection fraction of 40% or less who had an implanted cardioverter-defibrillator for primary or secondary prevention across three US tertiary hospitals were assessed in this retrospective, multicenter research (1998–2025). Patients needed continuous ICD follow-up and baseline Lp(a) readings, classified as <50 mg/dL or ≥50 mg/dL.
Delay to first suitable ICD shock for ventricular tachyarrhythmias was the major goal, and all-cause mortality, delay to first appropriate ICD treatment, and total shock burden were the secondary endpoints. Multivariable Cox proportional hazards models with non-arrhythmic fatalities censored were used to examine time-to-event data. The overall shock load was assessed using negative binomial regression, with statistical significance defined at a 2-sided P <.05.
190 of the 595 patients (median age 69; 76% male) who were monitored for around 7.1 years had elevated Lp(a) levels (≥50 mg/dL), whereas 405 had lower levels (<50 mg/dL). Particularly among primary-prevention ICD receivers, elevated Lp(a) was substantially linked to a greater incidence of suitable ICD shocks than the lower Lp(a) group (25.8% vs. 9.6%; adjusted hazard ratio [aHR], 2.95; P<.001).
Similarly, the increased Lp(a) cohort had a substantially higher composite result of adequate shock or antitachycardia pacing (31.6% vs. 15.3%; aHR, 2.37; P<.001).
Although a higher initial rate of suitable shocks was associated with increasing Lp(a), there was no significant difference in the recurring shock load among those who had at least one shock. The all-cause death rates of both groups stayed comparable.
Overall, the results emphasize the potential importance of increased Lp(a) as a biomarker for arrhythmic risk stratification by indicating that it may contribute to arrhythmogenesis through processes such as myocardial remodeling, fibrosis, and inflammation, irrespective of ischemic heart disease.
Reference:
Ibrahim, R., Dreher, L., Nabi, H. A., Farina, J. M., Habib, E., Pham, H. N., Tan, M. C., Noureldine, H. A., Ibrahim, S., Bhakta, M., Lee, K., Sorajja, D., Shen, W.-K., Scott, L. R., Ayoub, C., Arsanjani, R., & El Masry, H. Z. (2026). Lipoprotein(a) and risk of treated ventricular arrhythmias in heart failure. JAMA Network Open, 9(5), e2614674. https://doi.org/10.1001/jamanetworkopen.2026.14674
