CGRP rises after heart defect closure and may drive new-onset migraine that persists for years in some patients | Research

The takeaway

In 212 ASD closure patients, 20.3% developed new-onset migraine with significantly elevated post-closure CGRP (47.9 vs 38.0 pg/mL), predicted by young age, large ASD, and residual shunting, with 48% having unremitting migraine at 14-year follow-up.

CGRP elevated = migraine after heart repair
Post-ASD closure CGRP elevation was significantly associated with new-onset migraine, with 48% of cases persisting 14+ years—suggesting CGRP-targeted prevention

What the researchers found

New-onset migraine: 20.3% (43/212). CGRP elevated post-closure in migraine patients: 47.9 vs 38.0 pg/mL (p=0.023). NPY: no change. Predictors: young age (aOR 0.98), large ASD (aOR 1.07), residual shunting (aOR 2.78). Unremitting migraine: 48% at 14 years.

Why it matters

This reveals that CGRP—the target of modern migraine drugs—may be causally involved in post-cardiac-procedure migraine. Anti-CGRP therapy could potentially prevent or treat this common procedure complication.

How the study worked

Prospective cohort of 212 patients (2001-2013). Pre/post-closure echocardiography, CGRP and NPY levels. NOM assessment. 14-year telephone follow-up (2022).

What this study cannot tell us

Prospective but observational. CGRP measured in plasma (may not reflect brain levels). No intervention tested. Telephone follow-up for long-term migraine status. NPY not elevated—only CGRP implicated.

How to read the evidence

Prospective cohort with biomarker data and 14-year follow-up. Strong longitudinal evidence for CGRP involvement.

When this study was published

Published in 2025; cohort 2001-2013 with 2022 follow-up.

The bigger picture

This study bridges cardiology and neurology through neuropeptide biology. The CGRP elevation after cardiac procedures suggests a heart-brain neuropeptide axis that could be therapeutically targeted.

Questions still open

Could pre-treatment with anti-CGRP drugs prevent post-ASD-closure migraine?
What triggers CGRP release during cardiac procedures?
Should ASD closure patients at risk be offered migraine prophylaxis?

Common questions

Why do some people get migraines after heart repair?

This study found that the neuropeptide CGRP rises in the blood after ASD (heart hole) closure. In 20% of patients, this CGRP elevation triggers new-onset migraines. Risk factors include being young, having a larger hole, and having residual blood flow after the repair.

Do these migraines go away?

Unfortunately, only about half resolve within the first year. At 14-year follow-up, 48% of patients who developed post-procedure migraines still had them. Patients with larger shunts before closure were more likely to have persistent migraines. Anti-CGRP drugs (used for regular migraine) might help these patients.

Read the original research

The pathogenic role of calcitonin gene-related peptide and predictors of new-onset migraine and long-term outcomes after transcatheter atrial septal defect closure.

Headache, 65(5), 791-801

View on PubMed ↗Publisher’s paper ↗

Citation

Su, Tzu-Hsuan; Wang, Jou-Kou; Kuo, Ping-Hung; Chang, Shu-Hui; Chiou, Lih-Chu; Lee, Wang-Tso; Fan, Pi-Chuan. (2025). The pathogenic role of calcitonin gene-related peptide and predictors of new-onset migraine and long-term outcomes after transcatheter atrial septal defect closure.. Headache, 65(5), 791-801. https://doi.org/10.1111/head.14885